Molecular cell biology:
Gespeichert in:
| Format: | Buch |
|---|---|
| Sprache: | English |
| Veröffentlicht: |
New York
Freeman
2008
|
| Ausgabe: | 6. ed. |
| Schlagworte: | |
| Online-Zugang: | Buchbegleitseiten Inhaltsverzeichnis |
| Beschreibung: | Erg. bildet: Solutions manual to accompany Molecular cell biology. - Hier auch später erschienene, unveränderte Nachdrucke |
| Beschreibung: | Getr. Zählung Ill., graph. Darst. |
| ISBN: | 9781429203142 9780716776017 0716776014 |
Internformat
MARC
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Datensatz im Suchindex
| _version_ | 1804136594106482688 |
|---|---|
| adam_text | CONTENTS
Part I Chemical and Molecular Foundations
1
Cells Grow and Divide
Ceils Die from Aggravated Assault or an Internal Program
The Diversity and Commonality
of Cells
All Cells Are Prokaryotic or Eukaryotic
Unicellular Organisms Help and Hurt Us
Viruses Are the Ultimate Parasites
Changes in Cells Underlie Evolution
Even Single Cells Can Have Sex
We Develop from a Single Cell
Stem Cells, Fundamental to Forming Tissues
and Organs, Offer Medical Opportunities
The Molecules of a Cell
Small Molecules Carry Energy, Transmit Signals,
and Are Linked into Macromolecules
Proteins Give Cells Structure and Perform
Most Cellular Tasks
Nucleic Acids Carry Coded Information for Making
Proteins at the Right Time and Place
The Genome Is Packaged into Chromosomes and
Replicated During Cell Division
Mutations May Be Good, Bad, or Indifferent
The Work of Cells
Cells Build and Degrade Numerous Molecules
and Structures
Animal Cells Produce Their Own External
Environment and Glues
Cells Change Shape and Move
Cells Sense and Send Information
Cells Regulate Their Gene Expression to
Meet Changing Needs
Investigating Cells and Their Parts
Cell Biology Reveals the Size, Shape, Location,
and Movements of Cell Components
Biochemistry and Biophysics Reveal the Molecular
Structure and Chemistry of Purified Cell Constituents
Genetics Reveals the Consequences of Damaged Genes
Genomics Reveals Differences in the Structure
and Expression of Entire Genomes
Developmental Biology Reveals Changes in the
Properties of Cells as They Specialize
Choosing the Right Experimental Organism for the Job
The Most Successful Biological Studies Use Multiple
Approaches
A Genome Perspective on Evolution
Metabolic Proteins, the Genetic Code, and
Structures Are Nearly Universal
Darwin s Ideas About the Evolution of Whole Animals
Are Relevant to Genes
Many Genes Controlling Development Are Remarkably
Similar in Humans and Other Animals
Human Medicine Is Informed by Research on Other
Organisms
2
31
££| Covalent Bonds and Noncovalent
Interactions
The Electronic Structure of an Atom Determines the
Number and Geometry of Covalent Bonds It Can Make
CONTENTS
XV
Electrons
in
Covalent Bonds Are Much Stronger and More
Stable Than Noncovalent Interactions
Ionic Interactions Are Attractions between Oppositely
Charged Ions
Hydrogen Bonds Determine the Water Solubility
of Uncharged Molecules
Van
Transient Dipoles
The
Molecules to Adhere to One Another
Molecular Complementarity Mediated via
Noncovalent Interactions Permits Tight,
Highly Specific Binding of Biomolecules
Chemical Building Blocks of Cells
Amino
Compose Proteins
Five Different Nucleotides Are Used to Build
Nucleic Acids
Monosaccharides Joined by Glycosidic Bonds
Form Linear and Branched Polysaccharides
Phospholipids Associate Noncovalently to Form
the Basic Bilayer Structure of
£Щ
Equilibrium Constants Reflect the Extent of a
Chemical Reaction
Chemical Reactions in Cells Are at Steady State
Dissociation Constants of Binding Reactions Reflect
the Affinity of Interacting Molecules
Biological Fluids Have Characteristic
Hydrogen Ions Are Released by Acids and
Taken Up by Bases
Buffers Maintain the
Extracellular Fluids
Biochemical Energetics
Several Forms of Energy Are Important in
Biological Systems
Cells Can Transform One Type of Energy into Another
The Change in Free Energy Determines the Direction
of a Chemical Reaction
The
from Its K,
eq
The Rate of a Reaction Depends on the Activation
Energy Necessary to Energize the Reactants into
a Transition State
41
44
44
46
49
50
50
50
51
52
52
54
54
55
55
56
56
Life Depends on the Coupling of Unfavorable Chemical
Reactions with Energetically Favorable Reactions
Hydrolysis of ATP Releases Substantial Free Energy
and Drives Many Cellular Processes
ATP Is Generated During Photosynthesis and Respiration
NAD+ and FAD Couple Many Biological Oxidation
and Reduction Reactions
3
FUNCTION
^^| Hierarchical Structure of Proteins
The Primary Structure of a Protein Is Its Linear
Arrangement of
Secondary Structures Are the Core Elements
of Protein Architecture
Overall Folding of a Polypeptide Chain Yields
Its Tertiary Structure
Different Ways of Depicting the Conformation of
Proteins Convey Different Types of Information
Structural Motifs Are Regular Combinations of
Secondary and Tertiary Structures
Structural and Functional Domains Are Modules
of Tertiary Structure
Proteins Associate into
Macromolecular Assemblies
Members of Protein Families Have a Common
Evolutionary Ancestor
^^] Protein Folding
Planar
Which Proteins Can Fold
Information Directing a Protein s Folding Is
Encoded in Its
Folding of Proteins in Vivo Is Promoted by Chaperones
Alternatively Folded Proteins Are Implicated in Diseases
ЩЛ
Specific Binding of Ligands Underlies the
Functions of Most Proteins
Enzymes Are Highly Efficient and Specific Catalysts
An Enzyme s Active Site Binds Substrates and
Carries Out Catalysis
Serine
Enzyme s Active Site Works
Enzymes in a Common Pathway Are Often Physically
Associated with One Another
xvi
CONTENTS
Enzymes
into Motion
Regulating Protein Function I:
Protein Degradation
Regulated Synthesis and Degradation of Proteins
is a Fundamental Property of Cells
The Proteasome Is a Complex Molecular Machine
Used to Degrade Proteins
Ubiquitin Marks Cytosolic Proteins for Degradation
in Proteasomes
Q9I Regulating Protein Function II:
Noncovalent and Covalent
Modifications
Noncovalent Binding Permits Allosteric,
or Cooperative, Regulation of Proteins
Noncovalent Binding of Calcium and GTP Are Widely
Used As Allosteric Switches to Control Protein Activity
Phosphorylation and Dephosphorylation Covalently
Regulate Protein Activity
Proteolytic Cleavage Irreversibly Activates or
Inactivates Some Proteins
Higher-Order Regulation Includes Control of Protein
Location and Concentration
QQ Purifying, Detecting, and
Characterizing Proteins
Centrifugation Can Separate Particles and
Molecules That Differ in Mass or Density
Electrophoresis Separates Molecules on the Basis
of Their Charge-to-Mass Ratio
Liquid Chromatography Resolves Proteins by
Mass, Charge, or Binding Affinity
Highly Specific Enzyme and Antibody Assays Can
Detect Individual Proteins
Radioisotopes Are
Biological Molecules
Mass Spectrometry Can Determine the Mass
and Sequence of Proteins
Protein Primary Structure Can Be Determined by
Chemical Methods and from Gene Sequences
Protein Conformation Is Determined by Sophisticated
Physical Methods
Proteomics
Proteomics Is the Study of All or a Large Subset
of Proteins in a Biological System
Advanced Techniques in Mass Spectrometry Are
Critical to Proteomic Analysis
Part II Genetics and Molecular Biology
4
MECHANISMS
Structure of Nucleic Acids
A Nucleic Acid Strand Is a Linear Polymer with
End-to-End Directionality
Native
Antiparallel
DNA
Torsionai
Different Types of
Conformations Related to Their Functions
Q3 Transcription of Protein-Coding
Genes and Formation of Functional
mRNA
Organization of Genes Differs in Prokaryotic and
Eukaryotic
Eukaryotic Precursor mRNAs Are Processed to
Form Functional mRNAs
Alternative
Proteins Expressed from a Single Eukaryotic Gene
ШШШ
A Template
Complementary
Messenger
Three-Letter Genetic Code
The Folded Structure of tRNA Promotes Its Decoding
Functions
Nonstandard Base
Codons
Amino
Linked to tRNAs
Stepwise Synthesis of Proteins
on Ribosomes
120
127
129
130
131
132
132
CONTENTS
XVII
Meth¡onyl-tRNA¡MET
Translation Initiation Usually Occurs at the First
AUG
During Chain Elongation Each Incoming
Aminoacyl-tRNA Moves Through Three
Ribosomal Sites
Translation Is Terminated by Release Factors
When a Stop Codon Is Reached
Polysomes and Rapid Ribosome Recycling Increase
the Efficiency of Translation
IQ DNA
DNA Polymerases
Replication
Duplex
Formed at the
Several Proteins Participate in
DNA
Each Origin
ÜQ DNA
DNA
and Also Correct Them
Chemical and Radiation Damage to
Lead to Mutations
High-Fidelity DNA
Recognize and Repair Damage
Base Excision Repairs TG Mismatches and
Damaged Bases
Mismatch Excision Repairs Other Mismatches and
Small Insertions and Deletions
Nucleotide Excision Repairs Chemical Adducts
That Distort Normal
Two Systems Utilize Recombination to Repair
Double-Strand Breaks in
Homologous Recombination Can Repair
Damage and Generate Genetic Diversity
Viruses: Parasites of the Cellular
Genetic System
Most Viral Host Ranges Are Narrow
Viral Capsids Are Regular Arrays of One or a
Few Types of Protein
Viruses Can Be Cloned and Counted in Plaque Assays
Lytic Viral Growth Cycles Lead to the Death of Host Cells
Viral
in Some Nonlytic Viral Growth Cycles
5
Genetic Analysis of Mutations to
Identify and Study Genes
Recessive and Dominant Mutant
Have Opposite Effects on Gene Function
Segregation of Mutations in Breeding Experiments
Reveals Their Dominance or Recessivity
Conditional Mutations Can Be Used to Study
Essential Genes in Yeast
Recessive Lethal Mutations in Diploids Can Be
Identified by Inbreeding and Maintained in
Hétérozygotes
Complementation Tests Determine Whether Different
Recessive Mutations Are in the Same Gene
Double Mutants Are Useful in Assessing the Order
in Which Proteins Function
Genetic Suppression and Synthetic Lethality Can
Reveal Interacting or Redundant Proteins
Genes Can Be Identified by Their Map Position
on the Chromosome
171
173
174
ЩЦЩ
Restriction Enzymes and
Insertion of
E. coli Plasmid
Isolated
cDNA Libraries Represent the Sequences of
Protein-Coding Genes
cDNAs Prepared by Reverse Transcription of Cellular
mRNAs Can Be Cloned to Generate cDNA Libraries
DNA
to an Oligonucleotide Probe
Yeast Genomic Libraries Can Be Constructed with
Shuttle Vectors and Screened by Functional
Complementation
Gel Electrophoresis Allows Separation of Vector
DNA f
Cloned
by the Dideoxy Chain-Termination Method
The Polymerase Chain Reaction Amplifies a Specific
DNA
ШВШ
to Study Gene Expression
Hybridization Techniques Permit Detection
of Specific
DNA Microarrays
Expression of Many Genes at One Time
XVIII
CONTENTS
Cluster
Identifies Co-regulated Genes
E. coli
Quantities of Proteins from Cloned Genes
Plasmid Expression Vectors Can Be Designed for
Use in Animal Cells
Identifying and Locating Human
Disease Genes
Many Inherited Diseases Show One of Three Major
Patterns of Inheritance
DNA
Human Mutations
Linkage Studies Can Map Disease Genes with a
Resolution of About
Further Analysis Is Needed to Locate a Disease Gene
in Cloned
Many Inherited Diseases Result from Multiple Genetic
Defects
HQ Inactivating the Function of
Specific Genes in Eukaryotes
Normal Yeast Genes Can Be Replaced with Mutant
Alíeles
Transcription of Genes
Promoter Can Be Controlled Experimentally
Specific Genes Can Be Permanently Inactivated in
the Germ Line of Mice
Somatic Cell Recombination Can Inactivate Genes
in Specific Tissues
Dominant-Negative
Inhibit Some Genes
RNA
Destroying the Corresponding mRNA
6
CHROMOSOMES
Eukaryotic Gene Structure
217
Most Eukaryotic Genes Contain
mRNAs Encoding Single Proteins
Simple and Complex Transcription Units
Are Found in Eukaryotic Genomes
Protein-Coding Genes May Be Solitary or Belong
to a Gene Family
Heavily Used Gene Products Are Encoded by Multiple
Copies of Genes
Nonprotein-Coding Genes Encode Functional
RNAs
^2al Chromosomal Organization
of Genes and Noncoding
Genomes of Many Organisms Contain Much
Nonfunctional
Most Simple-Sequence DNAs Are Concentrated
in Specific Chromosomal Locations
DNA
in Length of Simple-Sequence DNAs
Unclassified Spacer
Portion of the Genome
(•Щ
Elements
Movement of Mobile Elements Involves a
DNA
DNA
and Eukaryotes
LTR Retrotransposons Behave Like Intracellular
Retroviruses
Non-LTR Retrotransposons Transpose by a Distinct
Mechanism
Other
DNA 234
Mobile
Evolution
ЦІ
Mitochondria Contain Multiple mtDNA Molecules
mtDNA Is Inherited Cytoplasmically
The Size, Structure, and Coding Capacity of mtDNA
Vary Considerably Between Organisms
Products of Mitochondrial Genes Are Not Exported
Mitochondria Evolved from a Single Endosymbiotic
Event Involving a
Mitochondrial Genetic Codes Differ from the
Standard Nuclear Code
Mutations in Mitochondrial
Genetic Diseases in Humans
Chloroplasts Contain Large DNAs Often Encoding
More Than a Hundred Proteins
Q3 Genomics: Genome-wide Analysis
of Gene Structure and Expression
Stored Sequences Suggest Functions of Newly
Identified Genes and Proteins
CONTENTS
XIX
Comparison of Related Sequences from Different
Species Can Give Clues to Evolutionary
Relationships Among Proteins
Genes Can Be Identified Within Genomic
Sequences
The Number of Protein-Coding Genes in an
Organism s Genome Is Not Directly Related
to Its Biological Complexity
Single Nucleotide Polymorphisms and Gene Copy-
Number Variation Are Important Determinants
of Differences Between Individuals of a Species
Structural Organization
of Eukaryotic Chromosomes
244
244
245
246
247
248
Chromatin Exists in Extended and Condensed Forms
Modifications of Histone Tails Control Chromatin
Condensation and Function
Nonhistone Proteins Provide a Structural Scaffold
for Long Chromatin Loops
Additional Nonhistone Proteins Regulate
Transcription and Replication
Small Molecules Regulate Expression of Many
Bacterial Genes via DNA-Binding Repressors
and Activators
Transcription Initiation from Some Promoters
Requires Alternative Sigma Factors
Transcription by aS4-RNA Polymerase Is Controlled
by Activators That Bind Far from the Promoter
Many Bacterial Responses Are Controlled by
Two-Component Regulatory Systems
EQI Overview of Eukaryotic Gene
Control and
Regulatory Elements in Eukaryotic
Both Close to and Many
Transcription Start Sites
Three Eukaryotic Polymerases Catalyze Formation
of Different RNAs
The Largest
Essential Carboxyl-Terminal Repeat
RNA
Sequences Corresponding to the
|эдЦ
of Eukaryotic Chromosomes
Chromosome Number, Size, and Shape at Metaphase
Are Species-Specific
During Metaphase, Chromosomes Can Be
Distinguished by Banding Patterns and
Chromosome Painting
Chromosome Painting and
the Evolution of Chromosomes
Interphase Polytene
Amplification
Three Functional Elements Are Required for Replication
and Stable Inheritance of Chromosomes
Centromere Sequences Vary Greatly in Length
Addition of Telomeric Sequences by Telomerase
Prevents Shortening of Chromosomes
TRANSCRIPTIONAL CONTROL
OF GENE EXPRESSION
269
Control of Gene Expression in
Bacteria
Transcription Initiation by Bacterial
Requires Association with a Sigma Factor
Initiation of lac Operon Transcription Can Be
Repressed and Activated
271
271
271
Цц|
Coding Genes
The TATA Box, Initiators, and CpG Islands Function
as Promoters in Eukaryotic
Promoter-Proximal Elements Help Regulate
Eukaryotic Genes
Distant Enhancers Often Stimulate Transcription
by
Most Eukaryotic Genes Are Regulated by Multiple
Transcription-Control Elements
Activators and Repressors of
Transcription
263
Interactions
Activators Are Modular Proteins Composed
of Distinct Functional Domains and Promote
Transcription
Repressors Inhibit Transcription and Are the
Functional Converse of Activators
DNA-Binding Domains Can Be Classified into
Numerous Structural Types
Structurally Diverse Activation and Repression
Domains Regulate Transcription
Transcription Factor Interactions Increase
Gene-Control Options
Multiprotein Complexes Form on Enhancers
282
282
282
284
285
286
286
288
290
290
293
294
295
xx
CONTENTS
Transcription Initiation
Polymerase II
296
General Transcription
Polymerase II
Sequential Assembly of Proteins Forms the Pol II
Transcription Preinitiation Complex in Vitro
In Vivo Transcription Initiation by Pol II Requires
Additional Proteins
Mitochondrial and
Transcribed by Organelle-Specific
Polymerases
317
8
CONTROL
Molecular Mechanisms of Transcription
Repression and Activation
Formation of Heterochromatin Silences Gene
Expression at Telomeres, Near Centromeres,
and in Other Regions
Repressors Can Direct Histone Deacetylation and
Methylation at Specific Genes
Activators Can Direct Histone Acetylation and
Methylation at Specific Genes
Chromatin-Remodeling Factors Help Activate or
Repress Transcription
299
299
303
305
306
Histone Modifications Vary Greatly in Their Stabilities
The Mediator Complex Forms a Molecular Bridge
Between Activation Domains and Pol II
307
Transcription of Many Genes Requires Ordered Binding
and Function of Activators and Co-activators
The Yeast Two-Hybrid System Exploits Activator Flexibility
to Detect cDNAs That Encode Interacting Proteins
Regulation of Transcription-Factor
Activity
Ali
Structure
312
Nuclear-Receptor Response Elements Contain Inverted
or Direct Repeats
Hormone Binding to a Nuclear Receptor Regulates Its
Activity as a Transcription Factor
Regulated Elongation and
Termination of Transcription
Transcription of the
an Antitermination Mechanism
Promoter-Proximal Pausing of
Occurs in Some Rapidly Induced Genes
Other Eukaryotic Transcription
Systems
Transcription Initiation by Pol I and Pol HI Is
Analogous to That by Pol II
313
314
315
316
316
316
Processing of Eukaryotic Pre-mRNA
The
Transcription Initiation
A Diverse Set of Proteins with Conserved RNA-Binding
Domains Associate with Pre-mRNAs
Splicing Occurs at Short, Conserved Sequences in
Pre-mRNAs via Two Transesterification Reactions
During Splicing, snRNAs Base-Pair with Pre-mRNA
Spliceosomes, Assembled from snRNPs and a
Pre-mRNA, Carry Out Splicing
Chain Elongation by
to the Presence of RNA-Processing Factors
SR Proteins Contribute to Exon Definition in Long
Pre-mRNAs
Self-Splicing Group II
Evolution of snRNAs
3
Are Tightly Coupled
Nuclear Exonucleases Degrade
Out of Pre-mRNAs
Ц2Л
Processing
Alternative Splicing Is the Primary Mechanism for
Regulating mRNA Processing
A Cascade of Regulated
Drosophila
Splicing Repressors and Activators Control Splicing
at Alternative Sites
RNA
Some Pre-mRNAs
£Q Transport of mRNA Across the
Nuclear Envelope
Nuclear Pore Complexes Control Import and Export
from the Nucleus
Pre-mRNAs in Spliceosomes Are Not Exported from
the Nucleus
HłV
Viral mRNAs
CONTENTS
XXI
Cytoplasmic
transcriptional Control
Micro RNAs Repress Translation of Specific mRNAs
RNA
Complementary mRNAs
Cytoplasmic Polyadenylation Promotes Translation
of Some mRNAs
Degradation of mRNAs in the Cytoplasm Occurs
by Several Mechanisms
Protein Synthesis Can Be Globally Regulated
Sequence-Specific RNA-Binding Proteins Control
Specific mRNA Translation
Surveillance Mechanisms Prevent Translation of
Improperly Processed mRNAs
Localization of mRNAs Permits Production of
Proteins at Specific Regions Within the
Cytoplasm
jjjjf Processing of rRNA and tRNA
Pre-rRNA Genes Function as Nucleolar Organizers
and Are Similar in All Eukaryotes
Small Nucleolar RNAs Assist in Processing Pre-rRNAs
Self-Splicing Group I
Examples of Catalytic
Pre-tRNAs Undergo Extensive Modification in the
Nucleus
Nuclear Bodies Are Functionally Specialized Nuclear
Domains
Part III Cell Structure and Function
VISUALIZING, FRACTIONATING,
AND CULTURING CELLS
Organelies
The Plasma Membrane Has Many Common Functions
in All Cells
Endosomes Take Up Soluble Macromolecules from
the Cell Exterior
Lysosomes Are Acidic
Battery of Degradative Enzymes
Peroxisomes Degrade Fatty Acids and Toxic Compounds
The Endoplasmic Reticulum Is a Network of
Interconnected Internal Membranes
The Golgi Complex Processes and Sorts Secreted
and Membrane Proteins
Plant
Cell to Elongate Rapidly
The Nucleus Contains the
Synthetic Apparatus, and a Fibrous Matrix
Mitochondria Are the Principal Sites of ATP
Production in Aerobic Nonphotosynthetic Cells
Chloroplasts Contain Internal Compartments in
Which Photosynthesis Takes Place
Light Microscopy: Visualizing Cell
Structure and Localizing Proteins
Within Cells
The Resolution of the Light Microscope Is About
0.2
381
Phase-Contrast and Differential Interference Contrast
Microscopy Visualize Unstained Living Cells
Fluorescence Microscopy Can Localize and Quantify
Specific Molecules in Live Cells
Imaging Subcellular Details Often Requires that the
Samples Be Fixed, Sectioned, and Stained
Immunofluorescence Microscopy Can Detect Specific
Proteins in Fixed Cells
Confocal and Deconvolution Microscopy Enable
Visualization of Three-Dimensional Objects
Graphics and Informatics Have Transformed
Modern Microscopy
Qfl Electron Microscopy: Methods
and Applications
Resolution of Transmission Electron Microscopy is
Vastly Greater Than That of Light Microscopy
Cryoelectron Microscopy Allows Visualization of
Particles Without Fixation or Staining
Electron Microscopy of Metal-Coated Specimens
Can Reveal Surface Features of Cells and Their
Components
Purification of Cell
Disruption of Cells Releases Their Organelles
and Other Contents
Centrifugation Can Separate Many Types of
Organelles
Organelle-Specific Antibodies Are Useful in
Preparing Highly Purified Organelles
xx»
CONTENTS
gşm
of Metazoan Cells
Flow Cytometry Separates Different Cell Types
Culture of Animal Cells Requires Nutrient-Rich
Media and Special Solid Surfaces
Primary Cell Cultures Can Be Used to Study Cell
Differentiation
Primary Cell Cultures and Cell Strains Have a Finite
Life Span
Transformed Cells Can Grow Indefinitely in Culture
Some Cell Lines Undergo Differentiation in Culture
Hybrid Cells Called
Monoclonal Antibodies
HAT Medium Is Commonly Used to Isolate
Hybrid Cells
Classic Experiment
10
409
Lipid-Binding Motifs Help Target Peripheral
Proteins to the Membrane
Proteins Can Be Removed from Membranes
by Detergents or High-Salt Solutions
QQ| Phospholipids, Sphingolipids,
and Cholesterol: Synthesis
and Intracellular Movement
Fatty Acids Synthesis Is Mediated by Several
Important Enzymes
Small Cytosolic Proteins Facilitate Movement of
Fatty Acids
Incorporation of Fatty Acids into Membrane Lipids
Takes Place on
Flippases Move Phospholipids from One Membrane
Leaflet to the Opposite Leaflet
Cholesterol Is Synthesized by Enzymes in the Cytosol
and
Cholesterol and Phospholipids Are Transported
Between
ШШ
and
Phospholipids Spontaneously Form Bilayers
Phospholipid Bilayers Form a Sealed Compartment
Surrounding an Internal Aqueous Space
Biomembranes
of Lipids
Most Lipids and Many Proteins Are Laterally Mobile
in
Lipid
Properties of Membranes
Lipid
and Cytosolic Leaflets
Cholesterol and Sphingolipids Cluster with Specific
Proteins in Membrane
Biomembranes:
and Basic Functions
Proteins Interact with Membranes in Three
Different Ways
Most
Membrane-Spanning
Multiple
Membrane-Spanning Barrels
Covalently Attached Hydrocarbon Chains Anchor
Some Proteins to Membranes
All
Asymmetrically Oriented in the Bilayer
11
OF IONS AND SMALL MOLECULES
Overview of Membrane
Transport
Only Small
by Simple Diffusion
Membrane Proteins Mediate Transport of
Most Molecules and All Ions Across
Biomembranes
Uniport Transport of Glucose
and Water
Several Features Distinguish Uniport Transport from
Simple Diffusion
GLUT1 Uniporter Transports Glucose into Most
Mammalian Cells
The Human Genome Encodes a Family of Sugar-
Transporting GLUT Proteins
Transport Proteins Can Be Enriched Within Artificial
Membranes and Cells
Osmotic Pressure Causes Water to Move Across
Membranes
Aquaporins Increase the Water Permeability of Cell
Membranes
CONTENTS
XXIII
ATP-Powered Pumps and the
Intracellular lonk Environment
Different Classes of Pumps
Structural and Functional Properties
ATP-Powered Ion Pumps Generate and
Maintain Ionic Gradients Across Cellular
Membranes
Muscle Relaxation Depends on Ca2+ ATPases That
Pump Ca2+ from the Cytosol into the
Sarcoplasmk Reticulum
Calmodulin Regulates the Plasma Membrane
Ca2+ Pumps That Control Cytosolic Ca2 1
Concentrations
Na+/K+ ATPase Maintains the Intracellular Na+
and K+ Concentrations in Animal Cells
V-Class H+ ATPases Maintain the Acidity of
Lysosomes and
Bacterial Permeases Are ABC Proteins That
Import a Variety of Nutrients from the
Environment
The Approximately
Play Diverse and Important Roles in Cell and
Organ Physiology
Certain ABC Proteins Flip Phospholipids
and Other Lipid-Soluble Substrates from
One Membrane Leaflet to the Opposite
Leaflet
Bacterial Symporter Structure Reveals the
Mechanism of Substrate Binding
Na+-Linked Ca2+ Antiporter Exports Ca2+ from
Cardiac Muscle Cells
Several Cotransporters Regulate
Cytosolic
A Putative Cation Exchange Protein Plays a
Key Role in Evolution of Human Skin
Pigmentation
Numerous Transport Proteins Enable Plant
Vacuoles
Transepithelial Transport
Multiple Transport Proteins Are Needed to
Move Glucose and
Epithelia
Simple Rehydration Therapy Depends on the
Osmotic Gradient Created by Absorption
of Glucose and Na+
Parietal Cells Acidify the Stomach Contents While
Maintaining a Neutral Cytosolic
Classic Experiment
Active Transport
12
479
Nongated Ion Channels and the
Resting Membrane Potential
Selective Movement of Ions Creates a
Transmembrane
Difference
The Membrane Potential in Animal Cells Depends
Largely on Potassium Ion Movements Through
Open Resting K+ Channels
Ion Channels Contain a Selectivity Filter Formed
from Conserved
Patch Clamps Permit Measurement of Ion
Movements Through Single Channels
Novel Ion Channels Can Be Characterized by a
Combination of Oocyte Expression and
Patch Clamping
Na+ Entry into Mammalian Cells Has a Negative
Change in Free Energy
Cotransport by Symporters and
Antiporters
Na+-Linked Symporters Import
Glucose into Animal Cells Against High
Concentration Gradients
First Steps of Glucose and Fatty
Acid Catabolism: Glycolysis
and the Citric Acid Cycle
During Glycolysis (Stage I), Cytosolic Enzymes
Convert Glucose to Pyruvate
The Rate of Glycolysis Is Adjusted to Meet
the Cell s Need for ATP
Glucose Is Fermented Under Anaerobic Conditions
Under Aerobic Conditions, Mitochondria
Efficiently Oxidize Pyruvate and Generate
ATP (Stages II-IV)
Mitochondria Are Dynamic
Structurally and Functionally Distinct Membranes
In Stage II, Pyruvate Is Oxidized to CO2 and High-
Energy Electrons Stored in Reduced Coenzymes
Transporters in the Inner Mitochondrial Membrane
Help Maintain Appropriate Cytosolic and Matrix
Concentrations of NAD+ and NADH
Mitochondrial Oxidation of Fatty Acids Generates
ATP
Peroxisomal Oxidation of Fatty Acids Generates
No ATP
480
481
483
485
485
485
487
489
491
491
xxiv
CONTENTS
The Electron Transport Chain and
Generation of the Proton-Motive
Force
Stepwise Electron Transport Efficiently Releases the
Energy Stored in NADH and FADH2
Electron Transport in Mitochondria Is Coupled to
Proton Pumping
Electrons Flow from FADH2 and NADH to O2
Through Four Multiprotein Complexes
Reduction Potentials of Electron Carriers Favor
Electron Flow from NADH to O2
Experiments Using Purified Complexes Established
the Stoichiometry of Proton Pumping
The
Translocated as Electrons Flow Through
Complex III
The Proton-Motive Force in Mitochondria Is Due
Largely to a Voltage Gradient Across the Inner
Membrane
Toxic By-products of Electron Transport Can
Damage Cells
ЦЮІ
Force for Energy-Requiring
Processes
The Mechanism of ATP Synthesis Is Shared
Among Bacteria, Mitochondria, and Chloroplasts
ATP Synthase Comprises Two Multiprotein
Complexes Termed Fo and F1
Rotation of the F,
Proton Movement Through Fo, Powers
ATP Synthesis
ATP-ADP Exchange Across the Inner Mitochondrial
Membrane Is Powered by the Proton-Motive
Force
Rate of Mitochondrial Oxidation Normally Depends
on ADP Levels
Brown-Fat Mitochondria Use the Proton-Motive
Force to Generate Heat
Photosynthesis and Light-Absorbing
Pigments
Thylakoid Membranes in Chloroplasts Are the Sites
of Photosynthesis in Plants
Three of the Four Stages in Photosynthesis Occur
Only During Illumination
Each Photon of Light Has a Defined Amount
of Energy
Photosystems
Associated Light-Harvesting Complexes
511
511
511
513
5Î4
Photoelectron Transport from Energized Reaction-
Center Chlorophyll a Produces a Charge
Separation
Internal Antenna and Light-Harvesting
Complexes Increase the Efficiency of
Photosynthesis
ЮЭ
Photosystems 517
The Single
Generates a Proton-Motive Force but No O2
Linear Electron Flow Through Both Plant
PSII and
O2, and NADPH
An Oxygen-Evolving Complex Is Located on
the
Center
Cells Use Multiple Mechanisms to Protect Against
Damage from Reactive Oxygen Species During
Photoelectron
Cyclic Electron Flow Through
Proton-Motive Force but No NADPH or O2
Relative Activities of
Regulated
ЮЗ
Photosynthesis
Rubisco Fixes CO2 in the Chloroplast
Synthesis of Sucrose Using Fixed CO2 Is Completed
in the Cytosol
Light and Rubisco
Fixation
Photorespiration,
Photosynthesis, Is Reduced in Plants That Fix
CO2 by the C4 Pathway
13
MEMBRANES AND ORGANELLES
Translocation
Across the
A
Nascent Secretory Proteins to the
Cotransiational
GTP-Hydrolyzing Proteins
Passage of Growing Polypeptides Through the
Translocon Is Driven by Energy Released During
Translation
CONTENTS
XXV
ATP Hydrolysis Powers Post-translational
Translocation
Insertion of Proteins into the
ER
Several Topological Classes of Integral Membrane
Proteins Are Synthesized on the
Internal Stop-Transfer and Signal-Anchor Sequences
Determine Topology of Single-Pass Proteins
Multipass Proteins Have Multiple Internal
Topogenic Sequences
A Phospholipid Anchor Tethers Some Cell-Surface
Proteins to the Membrane
The Topology of a Membrane Protein Often Can
Be Deduced from Its Sequence
Protein Modifications, Folding,
and Quality Control in the
A Preformed W-Linked Oligosaccharide Is Added to
Many Proteins in the Rough
Oligosaccharide Side Chains May Promote Folding
and Stability of Glycoproteins
Disulfide Bonds Are Formed and Rearranged by
Proteins in the
Chaperones and Other
and Assembly of Proteins
Improperly Folded Proteins in the
Expression of Protein-Folding Catalysts
Unassembled or Misfolded Proteins in the
Often Transported to the Cytosol for
Degradation
Sorting of Proteins to Mitochondria
and Chloroplasts
Amphipathic N-Terminal Signal Sequences Direct
Proteins to the Mitochondrial Matrix
558
Mitochondrial Protein Import Requires Outer-Membrane
Receptors and Translocons in Both Membranes
Studies with Chimeric Proteins Demonstrate Important
Features of Mitochondrial Import
Three Energy Inputs Are Needed to Import Proteins
into Mitochondria
Multiple Signals and Pathways Target Proteins to
Submitochondrial Compartments
Targeting of Chloroplast Stromal Proteins Is Similar to
Import of Mitochondrial Matrix Proteins
Proteins Are Targeted to Thylakoids by Mechanisms
Related to
Inner Membrane
Sorting of Peroxisomal Proteins
Cytosolic Receptor Targets Proteins with an SKL
Sequence at the C-Terminus into the Peroxisomal
Matrix
Peroxisomal Membrane and Matrix Proteins Are
Incorporated by Different Pathways
Transport into and out of the
Nucleus
Large and Small Molecules Enter and Leave the
Nucleus via Nuclear Pore Complexes
Importins Transport Proteins Containing Nuclear-
Localization Signals into the Nucleus
Exportins Transport Proteins Containing Nuclear-Export
Signals out of the Nucleus
Most mRNAs Are Exported from the Nucleus by a
Ran-lndependent Mechanism
14
AND ENDOCYTOSIS
Techniques for Studying the
Secretory Pathway
Transport of a Protein Through the Secretory
Pathway Can Be Assayed in Living Cells
Yeast Mutants Define Major Stages and Many
Components in Vesicular Transport
Cell-Free Transport Assays Allow Dissection of
Individual Steps in Vesicular Transport
Molecular Mechanisms of
Vesicular Traffic
Assembly of a Protein Coat Drives Vesicle
Formation and Selection of Cargo
Molecules
A Conserved Set of GTPase Switch Proteins Controls
Assembly of Different Vesicle Coats
Targeting Sequences on Cargo Proteins Make
Specific Molecular Contacts with Coat
Proteins
Rab
Membranes
Paired Sets of SNARE Proteins Mediate Fusion of
Vesicles with Target Membranes
Dissociation of SNARE Complexes After Membrane
Fusion Is Driven by ATP Hydrolysis
xxvi
CONTENTS
Early Stages of the Secretory
Pathway
592
COPII
to the Golgi
COPI Vesicles Mediate Retrograde Transport within
the Golgi and from the Golgi to the
Anterograde Transport Through the Golgi Occurs
by Cistemal Maturation
Later Stages of the Secretory
Pathway
Vesicles Coated with Clathrin and/or Adapter Proteins
Mediate Several Transport Steps
Dynamin Is Required for Pinching Off of Clathrin
Vesicles
Mannose 6-Phosphate Residues Target Soluble
Proteins to Lysosomes
Study of Lysosomal Storage Diseases Revealed Key
Components of the Lysosomal Sorting Pathway
Protein Aggregation in the frans-Golgi May Function
in Sorting Proteins to Regulated Secretory Vesicles
Some Proteins Undergo Proteolytic Processing
After Leaving the trans-Golgi
Several Pathways Sort Membrane Proteins to the
Apical or Basolateral Region of Polarized Cells
^QjU
Cells Take Up Lipids from the Blood in the Form of
Large, Weil-Defined Lipoprotein Complexes
Receptors for Low-Density Lipoprotein and Other
Ligands Contain Sorting Signals That Target
Them for Endocytosis
The Acidic
Receptor-Ligand Complexes to Dissociate
The Endocytic Pathway Delivers Iron to Cells without
Dissociation of the Receptor-Transferrin Complex
in Endosomes
Directing Membrane Proteins
and Cytosolic Materials to the
Lysosome
Multivesicular Endosomes Segregate Membrane
Proteins Destined for the Lysosomal
Membrane from Proteins Destined for
Lysosomal Degradation
Retroviruses Bud from the Plasma Membrane by a Process
Similar to Formation of Multivesicular Endosomes
15
TRANSDUCTION AND SHORT-TERM
CELLULAR RESPONSES
From Extracellular Signal to Cellular
Response
Signaling Cells Produce and Release Signaling
Molecules
Signaling Molecules Can Act Locally or at a Distance
Binding of Signaling Molecules Activates
Receptors on Target Cells
Щ5Щ
Receptors
Receptor Proteins Bind Ligands Specifically
The Dissociation Constant Is a Measure of the
Affinity of a Receptor for Its Ligand
Binding Assays Are Used to Detect Receptors and
Determine Their Affinities for Ligands
Maximal Cellular Response to a Signaling Molecule
Usually Does Not Require Activation of All
Receptors
Sensitivity of a Cell to External Signals Is Determined
by the Number of Surface Receptors and Their
Affinity for Ligand
Receptors Can Be Purified by Affinity Techniques
Classic Experiment
Out of the Cell
621
ЮЗ
of Intracellular Signal-Transduction
Pathways
GTP-Binding Proteins Are Frequently Used As On/Off
Switches
Protein Kinases and Phosphatases are Employed in
Virtually All Signaling Pathways
Second Messengers Carry and Amplify Signals from
Many Receptors
General Elements of
Coupled Receptor Systems
G
Family with a Common Structure and Function
G
GTP for GDP on the
Protein
Different
and in Turn Regulate Different Effector Proteins
CONTENTS
XXVII
щ^З
That Regulate Ion Channels
Acetylcholine Receptors in the Heart Muscle
Activate
Light Activates G^-Coupled Rhodopsins
Activation of Rhodopsin Induces Closing of
cGMP-Gated Cation Channels
Rod Cells Adapt to Varying Levels of Ambient Light
Because of Opsin Phosphorylation and Binding
of
Insulin and Glucagon Work Together to Maintain a
Stable Blood Glucose Level
658
Classic Experiment
Transduction—GTP Stimulation of cAMP Synthesis
16
PATHWAYS THAT CONTROL GENE
ACTIVITY
Ц22Я
Activate or Inhibit Adenylyl
Cyclase
Adenylyl Cyclase Is Stimulated and Inhibited
by Different Receptor-Ligand Complexes
Structural Studies Established How G^GTP Binds
to and Activates Adenylyl Cyclase
cAMP Activates Protein Kinase A by Releasing
Catalytic Subunits
Glycogen Metabolism Is Regulated by
Hormone-Induced Activation of Protein Kinase A
cAMP-Mediated Activation of Protein Kinase A
Produces Diverse Responses in Different Cell Types
Signal Amplification Commonly Occurs in Many
Signaling Pathways
Several Mechanisms Down-Regulate Signaling
from
Anchoring Proteins Localize Effects of cAMP to
Specific Regions of the Cell
QQI
Activate Phospholipase
Phosphorylated Derivatives of Inositol Are
Important Second Messengers
Calcium Ion Release from the
Reticulum is Triggered by IP3
The Ca2+/Calmodulin Complex Mediates Many
Cellular Responses to External Signals
Diacylglycerol (DAG) Activates Protein Kinase C,
Which Regulates Many Other Proteins
Signal-Induced Relaxation of Vascular Smooth
Muscle Is Mediated by cGMP-Activated
Protein Kinase
Integrating Responses of Cells
to Environmental Influences
Integration of Multiple Second Messengers Regulates
Glycogenolysis
TGFß
Activation of Smads
A
of an Inactive Precursor
Radioactive Tagging Was Used to Identify
Receptors
Activated
Transcription Factors
Negative Feedback Loops Regulate
Signaling
Loss of
in Cancer
Cytokine Receptors and the
JAK/STAT Pathway
Cytokines Influence Development of Many Cell
Types
Cytokine Receptors Have Similar Structures and
Activate Similar Signaling Pathways
JAK
Complementation Genetics Revealed That
JAK
Signals
Signaling from Cytokine Receptors Is Regulated
by Negative Signals
Mutant Erythropoietin Receptor That Cannot Be
Turned Off Leads to Increased Numbers of
Erythrocytes
Receptor Tyrosine Kinases
Ligand Binding Leads to Phosphorylation and
Activation of Intrinsic Kinase in RTKs
Overexpression of HER2, a Receptor
Tyrosine Kinase, Occurs in Some Breast
Cancers
XXVIII
CONTENTS
Conserved Domains Are Important for Binding Signal-
Transduction Proteins to Activated Receptors
Down-regulation of RTK Signaling Occurs by
Endocytosis and Lysosomal Degradation
Activation of
Pathways
Ras, a
and Inactive States
Receptor Tyrosine Kinases Are Linked to
Adapter Proteins
Genetic Studies in
Signal-Transducing Proteins in the Ras/MAP
Kinase Pathway
Binding of
Conformational Change That Activates
Signals Pass from Activated
Protein Kinases
MAP Kinase Regulates the Activity of Many Transcription
Factors Controlling Early-Response Genes
G
MAP Kinase in Yeast Mating Pathways
Scaffold Proteins Separate Multiple MAP Kinase
Pathways in Eukaryotic Cells
The Ras/MAP Kinase Pathway Can Induce Diverse
Cellular Responses
ЮЗ
Transducers
Phospholipase
Cytokine Receptors
Recruitment of PI-3 Kinase to Hormone-Stimulated
Receptors Leads to Synthesis of Phosphorylated
Phosphatidylinositols
Accumulation of PI 3-Phosphates in the Plasma
Membrane Leads to Activation of Several Kinases
Activated Protein Kinase
Cellular Responses
The PI-3 Kinase Pathway Is Negatively Regulated
by PTEN Phosphatase
Hedgehog Signaling Relieves Repression of Target
Genes
700
QQI Pathways That Involve Signal-Induced
Protein Cleavage
Degradation of an Inhibitor Protein Activates the
NF-kB Transcription Factors
Ligand-Activated Notch Is Cleaved Twice, Releasing
a Transcription Factor
Matrix Metalloproteases Catalyze Cleavage of Many
Signaling Proteins from the Cell Surface
Inappropriate Cleavage of Amyloid Precursor Protein
Can Lead to Alzheimer s Disease
Regulated Intramembrane Proteolysis of SREBP
Releases a Transcription Factor That Acts to
Maintain Phospholipid and Cholesterol Levels
17
MOVEMENT I:
Microfilaments
Structures
Actin Is Ancient, Abundant, and Highly Conserved
G-Actin Monomers Assemble into Long, Helical
F-Actin Polymers
F-Actin Has Structural and Functional Polarity
Dynamics of Actin Filaments
Actin Polymerization in Vitro Proceeds in Three Steps
Actin Filaments Grow Faster at
(-)
Actin Filament Treadmilling Is Accelerated by
Profilin
Thymosin-ß4
Polymerization
Capping Proteins Block Assembly and Disassembly
at Actin Filament Ends
720
721
722
722
Activation of Gene Transcription
by Seven-Spanning Cell-Surface
Receptors
CREB Links cAMP and Protein Kinase A to Activation
of Gene Transcription
GPCR-Bound Arrestin
Wnt Signals Trigger Release of a Transcription
Factor from Cytosolic Protein Complex
Mechanisms of Actin Filament
Assembly
Formins Assemble Unbranched Filaments
The Arp2/3 Complex Nucleates Branched Filament
Assembly
Intraceliular Movements Can Be Powered by Actin
Polymerization
CONTENTS
XXIX
Toxins That Perturb the Pool of Actin Monomers
Are Useful for Studying Actin Dynamics
726
Chemotactic Gradients Induce Altered Phosphoinositide
Levels Between the Front and Back of a Cell
Organization of Actin-Based Cellular
Structures
Cross-Linking Proteins Organize Actin Filaments into
Bundles or Networks
Adaptor Proteins Link Actin Filaments to
Membranes
Myosins: Actin-Based Motor
Proteins
Myosins Have Head, Neck, and Tail Domains with
Distinct Functions
Myosins Make Up a Large Family of
Mechanochemical Motor Proteins
Conformational Changes in the Myosin Head
Couple ATP Hydrolysis to Movement
Myosin Heads Take Discrete Steps Along
Actin Filaments
Myosin V Walks Hand Over Hand Down an Actin
Filament
Myosin-Powered Movements
Myosin Thick Filaments and Actin Thin Filaments
¡n Skeletal Muscle Slide Past One Another
During Contraction
Skeletal Muscle Is Structured by Stabilizing and
Scaffolding Proteins
Contraction of Skeletal Muscle Is Regulated by Ca2+
and Actin-Binding Proteins
Actin and Myosin II Form Contractile Bundles in
Nonmuscle Cells
Myosin-Dependent Mechanisms Regulate
Contraction in Smooth Muscle and Nonmuscle Cells
Myosin-V-Bound Vesicles Are Carried Along
Actin Filaments
Cell Migration: Signaling and
Chemotaxis
743
745
Cell Migration Coordinates Force Generation with
Cell Adhesion and Membrane Recycling
The Small GTP-Binding Proteins Cdc42,
Control Actin Organization
Cell Migration Involves the Coordinate Regulation
of Cdc42,
Migrating Cells Are Steered by Chemotactic
Molecules
Classic Experiment
Contraction
755
18
MOVEMENT II: MICROTUBULES
AND INTERMEDIATE FILAMENTS
Microtubule Structure and
Organization
Microtubule Walls Are Polarized Structures Built
from
Microtubules Are Assembled from MTOCs to
Generate Diverse Organizations
ЩЮЦ
Microtubules Are Dynamic Structures Due to
Kinetic Differences at Their Ends
Individual Microtubules Exhibit Dynamic Instability
Localized Assembly and Search-and-Capture
Help Organize Microtubules
Drugs Affecting Tubulin Polymerization Are Useful
Experimentally and to Treat Diseases
Regulation of Microtubule Structure
and Dynamics
Microtubules Are Stabilized by Side- and
End-Binding Proteins
Microtubules Are Disassembled by End Binding
and Severing Proteins
Kinesins and Dyneins: Microtubule-
Based Motor Proteins
Organelles in
Microtubules in Both Directions
Kinesin-1 Powers Anterograde Transport of
Vesicles Down
Microtubules
Kinesins Form a Large Protein Family with Diverse
Functions
Kinesin-1 Is a Highly
Dynein Motors Transport Organelles Toward the
End of Microtubules
Kinesins and Dyneins Cooperate in the Transport
of Organelles Throughout the Cell
xxx
CONTENTS
QQI Cilia
Based Surface Structures
Eukaryotic Cilia and
Microtubules Bridged by Dynein Motors
Ciliary and
Controlled Sliding of Outer Doublet
Microtubules
Intraflagellar Transport Moves Material Up and
Down Cilia and
Defects in Intraflagellar Transport Cause Disease
by Affecting Sensory Primary Cilia
ЦВДІ
Mitosis Can Be Divided into Six Phases
Centrosomes Duplicate Early in the Cell Cycle in
Preparation for Mitosis
The Mitotic Spindle Contains Three Classes of
Microtubules
Microtubule Dynamics Increases Dramatically
in Mitosis
Microtubules Treadmill During Mitosis
The Kinetochore Captures and Helps Transport
Chromosomes
Duplicated Chromosomes Are Aligned by Motors
and Treadmilling Microtubules
Anaphase
Microtubule Shortening
Anaphase
Action of Kinesins and Dynein
Additional Mechanisms Contribute to Spindle
Formation
Cytokinesis Splits the Duplicated Cell in Two
Plant Cells Reorganize Their Microtubules and
Build a New Cell Wall in Mitosis
ЦЦ2Л
Intermediate Filaments Are Assembled from
Subunit
Intermediate Filaments Proteins Are Expressed
in a Tissue-Specific Manner
Intermediate Filaments Are Dynamic
Defects in Lamins and Keratins Cause Many Diseases
Microfilaments
Transport Melanosomes
Cdc42 Coordinates Microtubules and
During Cell Migration
778
19
TISSUES
801
779
780
щущ
An Overview
803
Cell-Adhesion Molecules Bind to One Another and
781
to Intracellular Proteins
803
782
The Extracellular Matrix Participates in Adhesion,
Signaling, and Other Functions
805
783
The Evolution of Multifaceted Adhesion Molecules
Enabled the Evolution of Diverse Animal Tissues
807
784
ЦЦ
784
and Their Adhesion Molecules
808
785
Epithelial Cells Have Distinct Apical, Lateral, and
786
Basal Surfaces
808
Three Types of Junctions Mediate Many Cell-Cell
788
and Cell-ECM Interactions
809
Cadherins Mediate Cell-Cell Adhesions in Adherens
789
Junctions and Desmosomes
810
Tight Junctions Seal Off Body Cavities and Restrict
789
Diffusion of Membrane Components
814
Integrins
816
789
Gap Junctions Composed of Connexins Allow Small
789
Molecules to Pass Directly Between Adjacent Cells
817
Ц2Л
The Basal Lamina
The Basal Lamina Provides a Foundation for
Assembly of Cells into Tissues
Laminin, a Multiadhesive Matrix Protein, Helps
Cross-link Components of the Basal Lamina
Sheet-Forming Type IV Collagen Is a Major Structural
Component of the Basal Lamina
Perlecan, a Proteoglycan, Cross-links Components
of the Basal Lamina and Cell-Surface Receptors
Coordination and Cooperation
between Cytoskeletal Elements
Intermediate Filament-Associated Proteins
Contribute to Cellular Organization
ЕИ
Connective and Other Tissues
Fibrillar
in the ECM of Connective Tissues
CONTENTS
XXXI
Fibrillar
Fibrils Outside of the Cell
Type I and II
Collagens
Proteoglycans and Their Constituent GAGs Play
Diverse Roles in the ECM
Hyaluronan Resists Compression, Facilitates Cell Migration,
and Gives Cartilage Its Gel-like Properties
Fibronectins Interconnect Cells and Matrix, Influencing
Cell Shape, Differentiation, and Movement
Adhesive Interactions in Motile
and Nonmotile Cells
Integrins
Three-Dimensional Environment
Regulation of Integrin-Mediated Adhesion and
Signaling Controls Cell Movement
Connections Between the ECM and Cytoskeleton
Are Defective in Muscular Dystrophy
IgCAMs Mediate Cell-Cell Adhesion in
and Other Tissues
Leukocyte Movement into Tissues Is Orchestrated
by a Precisely Timed Sequence of Adhesive
Interactions
Plant Tissues
The Plant Cell Wall Is a Laminate of Cellulose Fibrils
in a Matrix of Glycoproteins
Loosening of the Cell Wall Permits Plant Cell
Growth
Plasmodesmata Directly Connect the Cytosols of
Adjacent Cells in Higher Plants
Only a Few Adhesive Molecules Have Been
Identified in Plants
Part IV Cell Growth and Development
20
CELL CYCLE
Overview of the Cell Cycle
and Its Control
The Cell Cycle Is an Ordered Series of Events
Leading to Cell Replication
Regulated Protein Phosphorylation and
Degradation Control Passage Through the
Cell Cycle
Diverse Experimental Systems Have Been Used to
Identify and Isolate Cell-Cycle Control Proteins
Control of Mitosis by Cyclins and
MPF Activity
Maturation-Promoting Factor (MPF) Stimulates
Meiotic Maturation in Oocytes and Mitosis
in Somatic Cells
Mitotic Cyclin Was First Identified in Early Sea
Urchin Embryos
Cyclin
Promoting Factor (MPF) Change Together in
Cycling Xenopus Egg Extracts
Anaphase-Promoting Complex (APC/C) Controls
Degradation of Mitotic Cyclins and Exit from
Mitosis
Cyclin-Dependent Kinase Regulation
During Mitosis
MPF Components Are Conserved Between Lower
and Higher Eukaryotes
Phosphorylation of the CDK
Kinase Activity of MPF
Conformational Changes Induced by Cyclin
Binding and Phosphorylation Increase
MPF Activity
Molecular Mechanisms for
Regulating Mitotic Events
Phosphorylation of Nuclear Lamins and Other
Proteins Promotes Early Mitotic Events
Unlinking of Sister Chromatids Initiates
Chromosome Decondensation and Reassembly of the
Nuclear Envelope Depend on Dephosphorylation
of MPF Substrates
Cyclin-CDK and Ubiquitin-Protein
Ligase
A Cyclin-Dependent Kinase (CDK) Is Critical for
S-Phase Entry in
Three
to Form S-Phase-Promoting Factors
xxxii
CONTENTS
Degradation
Replication
Multiple Cyclins Regulate the Kinase Activity of
S. cerevisiae CDK During Different Cell-Cycle Phases
Replication at Each Origin Is Initiated Only Once
During the Cell Cycle
gţjiBSfl
Cells
Mammalian Restriction Point Is Analogous to
START in Yeast Cells
Multiple CDKs and Cyclins Regulate Passage of
Mammalian Cells Through the Cell Cycle
Regulated Expression of Two Classes of Genes
Returns Go Mammalian Cells to the Cell Cycle
Passage Through the Restriction Point Depends on
Phosphorylation of the Tumor-Suppressor Rb Protein
Cyclin A Is Required for
for Entry into Mitosis
Two Types of Cyclin-CDK Inhibitors Contribute to
Cell-Cycle Control in Mammals
ЕШЛ
Regulation
The Presence of Unreplicated
into Mitosis
Improper Assembly of the Mitotic Spindle Prevents
the Initiation of
Proper Segregation of Daughter Chromosomes Is
Monitored by the Mitotic Exit Network
Cell-Cycle Arrest of Cells with Damaged
on Tumor Suppressors
ЩЦ
Division
892
892
Key Features Distinguish Meiosis from Mitosis
Repression of
Kinase Promote Premeiotic
Recombination and a Meiosis-Specific Cohesin
Are Necessary for the Specialized Chromosome
Segregation in Meiosis I
Special Properties of Rec8 Regulate Its Cleavage in
Meiosis I and II
The
Kinetochores in Meiosis I
Tension on Spindle Microtubules Contributes to
Proper Spindle Attachment
895
896
898
898
Classic Experiment
from the Sea: The Discovery of Cyclins
21
DEATH
The Birth of Cells: Stem Cells,
Niches, and Lineage
Stem Cells Give Rise to Both Stem Cells and
Differentiating Cells
Cell Fates Are Progressively Restricted During
Development
The Complete Cell Lineage of
Heterochronic Mutants Provide Clues About Control
of Cell Lineage
Cultured Embryonic Stem Cells Can Differentiate into
Various Cell Types
Adult Stem Cells for Different Animal Tissues Occupy
Sustaining Niches
Meristems Are
Plants
ЩЩ
Mating-Type Transcription Factors Specify
Cell Types
MCM1 and
Transcription
аг-МСМІ
Pheromones Induce Mating of
Generate a Third Cell Type
Specification and Differentiation
of Muscle
Embryonic Somites Give Rise to Myoblasts
Myogenic Genes Were First Identified in Studies with
Cultured
Two Classes of Regulatory Factors Act in Concert to
Guide Production of Muscle Cells
Differentiation of Myoblasts Is Under Positive and
Negative Control
Cell-Cell Signals Are Crucial for Determination and
Migration of Myoblasts
bHLH Regulatory Proteins Function in Creation of
Other Tissues
Regulation of Asymmetric
Cell Division
Yeast Mating-Type Switching Depends upon
Asymmetric Cell Division
CONTENTS
XXXIII
Proteins
Opposite Ends of Dividing Neuroblasts in
Cell Death and Its Regulation
Programmed Cell Death Occurs Through Apoptosis
Neurotrophins Promote Survival of Neurons
A Cascade of Caspase Proteins Functions in One
Apoptotic Pathway
Pro-Apoptotic Regulators Permit Caspase Activation
in the Absence of Trophic Factors
Some Trophic Factors Induce Inactivation of
a Pro-Apoptotic Regulator
Tumor Necrosis Factor and Related Death Signals
Promote Cell Murder by Activating Caspases
22
OF DEVELOPMENT
Highlights of Development
(ЩЩ
Germ-line Cells Are All That We Inherit
Fertilization Unifies the Genome
Genomic Imprinting Controls Gene Activation
According to Maternal or Paternal Chromosome
Origin
Too Much of a Good Thing: The X Chromosome Is
Regulated by Dosage Compensation
in Early Vertebrate Embryos
Cleavage Leads to the First Differentiation Events
The Genomes of Most Somatic Cells Are Complete
Gastrulation Creates Multiple Tissue Layers, Which
Become Polarized
Signal Gradients May Induce Different Cell Fates
Signal Antagonists Influence Cell Fates and Tissue
Induction
A Cascade of Signals Distinguishes Left from Right
950
Development Progresses from Egg and Sperm
to an Early Embryo
As the Embryo Develops, Cell Layers Become Tissues
and Organs
Genes That Regulate Development Are at the
Heart of Evolution
952
953
953
955
958
958
959
960
961
961
963
965
966
Control of Body Segmentation:
Themes and Variations in Insects
and Vertebrates
Early
Transcriptional Control Specifies the Embryo s
Anterior and Posterior
Translation Inhibitors Reinforce Anterior-Posterior
Patterning
Insect Segmentation Is Controlled by a Cascade
of Transcription Factors
Vertebrate Segmentation Is Controlled by Cyclical
Expression of Regulatory Genes
Differences Between Segments Are Controlled by
Hox Genes
Hox-Gene Expression Is Maintained by a Variety
of Mechanisms
Flower Development Requires Spatially Regulated
Production of Transcription Factors
Cell-Type Specification in Early
Neural Development
Neurulation Begins Formation of the Brain and
Spinal Cord
Signal Gradients and Transcription Factors Specify Cell
Types in the Neural Tube and Somites
Most Neurons in the Brain Arise in the Innermost
Neural Tube and Migrate Outward
Lateral Inhibition Mediated by Notch Signaling
Causes Early Neural Cells to Become Different
Growth and Patterning of Limbs
Hox Genes Determine the Right Places for
Limbs to Grow
Limb Development Depends on Integration
of Multiple Extracellular Signal Gradients
Hox Genes Also Control Fine Patterning
of Limb Structures
So Far, So Good
Classic Experiment
Mutations to Study Development
990
991
992
994
999
23
949
Neurons and
Blocks of the Nervous System
Information Flows Through Neurons from
to
xxxiv
CONTENTS
Information Moves as Pulses of Ion Flow Called
Action Potentials
Information Flows Between Neurons via
Synapses
The Nervous System Uses Signaling Circuits
Composed of Multiple Neurons
Q29 Voltage-Gated Ion Channels
and the Propagation of Action
Potentials in Nerve Cells
The Magnitude of the Action Potential Is Close
to £Na
Sequential Opening and Closing of Voltage-
Gated Na+ and K+ Channels Generate Action
Potentials
Action Potentials Are Propagated Unidirectionally
Without Diminution
Nerve Cells Can Conduct Many Action Potentials
in the Absence of ATP
All Voltage-Gated Ion Channels Have Similar
Structures
Voltage-Sensing S4
to Membrane Depolarization
Movement of the Channel-Inactivating Segment
into the Open Pore Blocks Ion Flow
Myelination Increases the Velocity of Impulse
Conduction
Action Potentials Jump from Node to Node
in Myelinated
Glia
QQI Communication at Synapses
Formation of Synapses Requires Assembly of
Presynaptic and Postsynaptic Structures
Neurotransmitters
Vesicles by H^Linked Antiport Proteins
Synaptic Vesicles Loaded with
Are Localized near the Plasma Membrane
Influx of Ca2+ Triggers Release of
Neurotransmitters
A Calcium-Binding Protein Regulates Fusion of
Synaptic Vesicles with the Plasma Membrane
Signaling at Synapses Is Terminated by Degradation
or Reuptake of
Fly Mutants Lacking Dynamin Cannot Recycle
Synaptic Vesicles
Opening of Acetylcholine-Gated Cation Channels
Leads to Muscle Contraction
All Five Subunits in the Nicotinic Acetylcholine
Receptor Contribute to the Ion Channel
Nerve Cells Make an All-or-None Decision to
Generate an Action Potential
Gap Junctions Also Allow Neurons to Communicate
ЕЭД
Hearing, Tasting, and Smelling
The Eye Features Light-Sensitive Nerve Cells
Eyes Reflect Evolutionary History
Integrated Information from Multiple Ganglion
Cells Forms Images of the World
Mechanosensory Cells Detect Pain, Heat, Cold,
Touch, and Pressure
Inner Ear Cells Detect Sound and Motion
Five Primary Tastes Are Sensed by Subsets of Cells
in Each Taste Bud
A Plethora of Receptors Detect Odors
The Path to Success: Controlling
Axon Growth and Targeting
The Growth Cone Is a Motorized Sensory
Guidance Structure
The Retinotectal Map Revealed an Ordered
System of Axon Connections
There Are Four Families of Axon Guidance
Molecules
Developmental Regulators Also Guide
Axon Guidance Molecules Cause the Growth
Cone to Turn
24
1055
ОЛ
Pathogens Enter the Body Through Different
Routes and Replicate at Different Sites
Leukocytes Circulate Throughout the Body and
Take Up Residence in Tissues and Lymph Nodes
Mechanical and Chemical Boundaries Form
a First Layer of Defense Against Pathogens
Innate Immunity Provides a Second Line
of Defense After Mechanical and Chemical
Barriers Are Crossed
Inflammation Is a Complex Response to Injury That
Encompasses Both Innate and Adaptive Immunity
Adaptive Immunity, the Third Line of Defense,
Exhibits Specificity
CONTENTS
XXXV
QQI Immunoglobulins:
and Function
Immunoglobulins Have a Conserved Structure
Consisting of Heavy and Light Chains
Multiple Immunoglobulin
Each with Different Functions
Each
Immunoglobulin
Immunoglobulin Domains Have a Characteristic Fold
Composed of Two
by a Disulfide Bond
The Three-Dimensional Structure of Antibody
Molecules Accounts for Their Exquisite
Specificity
An Immunoglobulin s Constant Region Determines Its
Functional Properties
Generation of Antibody Diversity
and B-Cell Development
A Functional Light-Chain Gene Requires Assembly
of V and
Rearrangement of the Heavy-Chain Locus Involves
V, D, and
Somatic Hypermutation Allows the Generation
and Selection of Antibodies with Improved
Affinities
B-Cell Development Requires Input from a
Pre-B Cell Receptor
During an Adaptive Response,
from Making Membrane-Bound
Secreted
В
They Make
The MHC and Antigen
Presentation
The MHC Determines the Ability of Two Unrelated
Individuals of the Same Species
to Accept or Reject Grafts
The Killing Activity of Cytotoxic
Specific and MHC Restricted
T
Guided by Two Distinct Classes of MHC Molecules
MHC Molecules Bind
and Interact with the
Antigen Presentation Is the Process by Which
Protein Fragments Are Complexed with MHC
Products and Posted to the Cell Surface
Class I MHC Pathway Presents Cytosolic Antigens
Class II MHC Pathway Presents Antigens Delivered
to the Endocytic Pathway
1082
1082
1084
T
and
The Structure of the
the F(ab) Portion of an Immunoglobulin
TCR Genes Are Rearranged in a Manner Similar to
Immunoglobulin Genes
Т
of Their Variable Residues Encoded in the
Junctions between V, D, and
Signaling via Antigen-Specific Receptors Triggers
Proliferation and Differentiation
of
T
Develop Through a Process of Positive
and Negative Selection
T
for Full Activation
Cytotoxic
and Are Specialized for Killing
T
Signals to Other Immune Cells
CD4
Based on Their Cytokine Production
and Expression of Surface Markers
Leukocytes Move in Response to Chemotactic Cues
Provided by Chemokines
Collaboration of Immune-System
Cells in the Adaptive Response
Toll-Like Receptors Perceive a Variety
of Pathogen-Derived Macromolecular Patterns
Engagement of Toll-Like Receptors Leads
to Activation of Antigen-Presenting Cells
Production of High-Affinity Antibodies Requires
Collaboration Between
Vaccines Elicit Protective Immunity Against
a Variety of Pathogens
Classic Experiment
Somatic Rearrangement of Immunoglobulin Genes
25
1107
Tumor Cells and the Onset
of Cancer
1109
Metastatic Tumor Cells Are Invasive and Can Spread
Cancers Usually Originate in Proliferating Cells
Cancer Stem Cells Can Be a Minority Population
Tumor Growth Requires Formation of
New Blood Vessels
1111
xxxvi
CONTENTS
Specific
into Tumor Cells
A Multi-hit Model of Cancer Induction Is Supported
by Several Lines of Evidence
Successive Oncogenic Mutations Can Be Traced
in Colon Cancers
DNA Microarray
Reveal Subtle Differences Between Tumor Cells
££2Ш
Gain-of-Function Mutations Convert Proto-oncogenes
into Oncogenes
Cancer-Causing Viruses Contain Oncogenes or
Activate Cellular Proto-oncogenes
Loss-of-Function Mutations in Tumor-Suppressor
Genes Are Oncogenic
Inherited Mutations in Tumor-Suppressor Genes
Increase Cancer Risk
Aberrations in Signaling Pathways That Control
Development Are Associated with Many Cancers
^Ц£|
Promoting Proteins
Oncogenic Receptors Can Promote Proliferation in
the Absence of External Growth Factors
Viral Activators of Growth-Factor Receptors Act
as Oncoproteins
Many Oncogenes Encode Constitutively Active
Signal-Transduction Proteins
Inappropriate Production of Nuclear Transcription
Factors Can Induce Transformation
Molecular Cell Biology Is Changing How Cancer
Is Treated
О2Я
Growth-Inhibiting and
Cell-Cycle Controls
Mutations That Promote Unregulated Passage from
G, to
Loss-of-Function Mutations Affecting Chromatin-
Remodeling Proteins Contribute to Tumors
Loss of p53 Abolishes the DNA-Damage Checkpoint
Apoptotic Genes Can Function as Proto-oncogenes
or Tumor-Suppressor Genes
Failure of Cell-Cycle Checkpoints Often Leads to
Aneuploidy in Tumor Cells
Carcinogens and Caretaker Genes
in Cancer
Carcinogens Induce Cancer by Damaging
Some Carcinogens Have Been Linked to
Specific Cancers
Loss of DNA-Repair Systems Can Lead to Cancer
Telomerase Expression Contributes to
Immortalization of Cancer Cells
GLOSSARY G-1
INDEX
CONTENTS
XXXVII
|
| adam_txt |
CONTENTS
Part I Chemical and Molecular Foundations
1
Cells Grow and Divide
Ceils Die from Aggravated Assault or an Internal Program
The Diversity and Commonality
of Cells
All Cells Are Prokaryotic or Eukaryotic
Unicellular Organisms Help and Hurt Us
Viruses Are the Ultimate Parasites
Changes in Cells Underlie Evolution
Even Single Cells Can Have Sex
We Develop from a Single Cell
Stem Cells, Fundamental to Forming Tissues
and Organs, Offer Medical Opportunities
The Molecules of a Cell
Small Molecules Carry Energy, Transmit Signals,
and Are Linked into Macromolecules
Proteins Give Cells Structure and Perform
Most Cellular Tasks
Nucleic Acids Carry Coded Information for Making
Proteins at the Right Time and Place
The Genome Is Packaged into Chromosomes and
Replicated During Cell Division
Mutations May Be Good, Bad, or Indifferent
The Work of Cells
Cells Build and Degrade Numerous Molecules
and Structures
Animal Cells Produce Their Own External
Environment and Glues
Cells Change Shape and Move
Cells Sense and Send Information
Cells Regulate Their Gene Expression to
Meet Changing Needs
Investigating Cells and Their Parts
Cell Biology Reveals the Size, Shape, Location,
and Movements of Cell Components
Biochemistry and Biophysics Reveal the Molecular
Structure and Chemistry of Purified Cell Constituents
Genetics Reveals the Consequences of Damaged Genes
Genomics Reveals Differences in the Structure
and Expression of Entire Genomes
Developmental Biology Reveals Changes in the
Properties of Cells as They Specialize
Choosing the Right Experimental Organism for the Job
The Most Successful Biological Studies Use Multiple
Approaches
A Genome Perspective on Evolution
Metabolic Proteins, the Genetic Code, and
Structures Are Nearly Universal
Darwin's Ideas About the Evolution of Whole Animals
Are Relevant to Genes
Many Genes Controlling Development Are Remarkably
Similar in Humans and Other Animals
Human Medicine Is Informed by Research on Other
Organisms
2
31
££| Covalent Bonds and Noncovalent
Interactions
The Electronic Structure of an Atom Determines the
Number and Geometry of Covalent Bonds It Can Make
CONTENTS
XV
Electrons
in
Covalent Bonds Are Much Stronger and More
Stable Than Noncovalent Interactions
Ionic Interactions Are Attractions between Oppositely
Charged Ions
Hydrogen Bonds Determine the Water Solubility
of Uncharged Molecules
Van
Transient Dipoles
The
Molecules to Adhere to One Another
Molecular Complementarity Mediated via
Noncovalent Interactions Permits Tight,
Highly Specific Binding of Biomolecules
Chemical Building Blocks of Cells
Amino
Compose Proteins
Five Different Nucleotides Are Used to Build
Nucleic Acids
Monosaccharides Joined by Glycosidic Bonds
Form Linear and Branched Polysaccharides
Phospholipids Associate Noncovalently to Form
the Basic Bilayer Structure of
£Щ
Equilibrium Constants Reflect the Extent of a
Chemical Reaction
Chemical Reactions in Cells Are at Steady State
Dissociation Constants of Binding Reactions Reflect
the Affinity of Interacting Molecules
Biological Fluids Have Characteristic
Hydrogen Ions Are Released by Acids and
Taken Up by Bases
Buffers Maintain the
Extracellular Fluids
Biochemical Energetics
Several Forms of Energy Are Important in
Biological Systems
Cells Can Transform One Type of Energy into Another
The Change in Free Energy Determines the Direction
of a Chemical Reaction
The
from Its K,
eq
The Rate of a Reaction Depends on the Activation
Energy Necessary to Energize the Reactants into
a Transition State
41
44
44
46
49
50
50
50
51
52
52
54
54
55
55
56
56
Life Depends on the Coupling of Unfavorable Chemical
Reactions with Energetically Favorable Reactions
Hydrolysis of ATP Releases Substantial Free Energy
and Drives Many Cellular Processes
ATP Is Generated During Photosynthesis and Respiration
NAD+ and FAD Couple Many Biological Oxidation
and Reduction Reactions
3
FUNCTION
^^| Hierarchical Structure of Proteins
The Primary Structure of a Protein Is Its Linear
Arrangement of
Secondary Structures Are the Core Elements
of Protein Architecture
Overall Folding of a Polypeptide Chain Yields
Its Tertiary Structure
Different Ways of Depicting the Conformation of
Proteins Convey Different Types of Information
Structural Motifs Are Regular Combinations of
Secondary and Tertiary Structures
Structural and Functional Domains Are Modules
of Tertiary Structure
Proteins Associate into
Macromolecular Assemblies
Members of Protein Families Have a Common
Evolutionary Ancestor
^^] Protein Folding
Planar
Which Proteins Can Fold
Information Directing a Protein's Folding Is
Encoded in Its
Folding of Proteins in Vivo Is Promoted by Chaperones
Alternatively Folded Proteins Are Implicated in Diseases
ЩЛ
Specific Binding of Ligands Underlies the
Functions of Most Proteins
Enzymes Are Highly Efficient and Specific Catalysts
An Enzyme's Active Site Binds Substrates and
Carries Out Catalysis
Serine
Enzyme's Active Site Works
Enzymes in a Common Pathway Are Often Physically
Associated with One Another
xvi
CONTENTS
Enzymes
into Motion
Regulating Protein Function I:
Protein Degradation
Regulated Synthesis and Degradation of Proteins
is a Fundamental Property of Cells
The Proteasome Is a Complex Molecular Machine
Used to Degrade Proteins
Ubiquitin Marks Cytosolic Proteins for Degradation
in Proteasomes
Q9I Regulating Protein Function II:
Noncovalent and Covalent
Modifications
Noncovalent Binding Permits Allosteric,
or Cooperative, Regulation of Proteins
Noncovalent Binding of Calcium and GTP Are Widely
Used As Allosteric Switches to Control Protein Activity
Phosphorylation and Dephosphorylation Covalently
Regulate Protein Activity
Proteolytic Cleavage Irreversibly Activates or
Inactivates Some Proteins
Higher-Order Regulation Includes Control of Protein
Location and Concentration
QQ Purifying, Detecting, and
Characterizing Proteins
Centrifugation Can Separate Particles and
Molecules That Differ in Mass or Density
Electrophoresis Separates Molecules on the Basis
of Their Charge-to-Mass Ratio
Liquid Chromatography Resolves Proteins by
Mass, Charge, or Binding Affinity
Highly Specific Enzyme and Antibody Assays Can
Detect Individual Proteins
Radioisotopes Are
Biological Molecules
Mass Spectrometry Can Determine the Mass
and Sequence of Proteins
Protein Primary Structure Can Be Determined by
Chemical Methods and from Gene Sequences
Protein Conformation Is Determined by Sophisticated
Physical Methods
Proteomics
Proteomics Is the Study of All or a Large Subset
of Proteins in a Biological System
Advanced Techniques in Mass Spectrometry Are
Critical to Proteomic Analysis
Part II Genetics and Molecular Biology
4
MECHANISMS
Structure of Nucleic Acids
A Nucleic Acid Strand Is a Linear Polymer with
End-to-End Directionality
Native
Antiparallel
DNA
Torsionai
Different Types of
Conformations Related to Their Functions
Q3 Transcription of Protein-Coding
Genes and Formation of Functional
mRNA
Organization of Genes Differs in Prokaryotic and
Eukaryotic
Eukaryotic Precursor mRNAs Are Processed to
Form Functional mRNAs
Alternative
Proteins Expressed from a Single Eukaryotic Gene
ШШШ
A Template
Complementary
Messenger
Three-Letter Genetic Code
The Folded Structure of tRNA Promotes Its Decoding
Functions
Nonstandard Base
Codons
Amino
Linked to tRNAs
Stepwise Synthesis of Proteins
on Ribosomes
120
127
129
130
131
132
132
CONTENTS
XVII
Meth¡onyl-tRNA¡MET
Translation Initiation Usually Occurs at the First
AUG
During Chain Elongation Each Incoming
Aminoacyl-tRNA Moves Through Three
Ribosomal Sites
Translation Is Terminated by Release Factors
When a Stop Codon Is Reached
Polysomes and Rapid Ribosome Recycling Increase
the Efficiency of Translation
IQ DNA
DNA Polymerases
Replication
Duplex
Formed at the
Several Proteins Participate in
DNA
Each Origin
ÜQ DNA
DNA
and Also Correct Them
Chemical and Radiation Damage to
Lead to Mutations
High-Fidelity DNA
Recognize and Repair Damage
Base Excision Repairs TG Mismatches and
Damaged Bases
Mismatch Excision Repairs Other Mismatches and
Small Insertions and Deletions
Nucleotide Excision Repairs Chemical Adducts
That Distort Normal
Two Systems Utilize Recombination to Repair
Double-Strand Breaks in
Homologous Recombination Can Repair
Damage and Generate Genetic Diversity
Viruses: Parasites of the Cellular
Genetic System
Most Viral Host Ranges Are Narrow
Viral Capsids Are Regular Arrays of One or a
Few Types of Protein
Viruses Can Be Cloned and Counted in Plaque Assays
Lytic Viral Growth Cycles Lead to the Death of Host Cells
Viral
in Some Nonlytic Viral Growth Cycles
5
Genetic Analysis of Mutations to
Identify and Study Genes
Recessive and Dominant Mutant
Have Opposite Effects on Gene Function
Segregation of Mutations in Breeding Experiments
Reveals Their Dominance or Recessivity
Conditional Mutations Can Be Used to Study
Essential Genes in Yeast
Recessive Lethal Mutations in Diploids Can Be
Identified by Inbreeding and Maintained in
Hétérozygotes
Complementation Tests Determine Whether Different
Recessive Mutations Are in the Same Gene
Double Mutants Are Useful in Assessing the Order
in Which Proteins Function
Genetic Suppression and Synthetic Lethality Can
Reveal Interacting or Redundant Proteins
Genes Can Be Identified by Their Map Position
on the Chromosome
171
173
174
ЩЦЩ
Restriction Enzymes and
Insertion of
E. coli Plasmid
Isolated
cDNA Libraries Represent the Sequences of
Protein-Coding Genes
cDNAs Prepared by Reverse Transcription of Cellular
mRNAs Can Be Cloned to Generate cDNA Libraries
DNA
to an Oligonucleotide Probe
Yeast Genomic Libraries Can Be Constructed with
Shuttle Vectors and Screened by Functional
Complementation
Gel Electrophoresis Allows Separation of Vector
DNA f
Cloned
by the Dideoxy Chain-Termination Method
The Polymerase Chain Reaction Amplifies a Specific
DNA
ШВШ
to Study Gene Expression
Hybridization Techniques Permit Detection
of Specific
DNA Microarrays
Expression of Many Genes at One Time
XVIII
CONTENTS
Cluster
Identifies Co-regulated Genes
E. coli
Quantities of Proteins from Cloned Genes
Plasmid Expression Vectors Can Be Designed for
Use in Animal Cells
Identifying and Locating Human
Disease Genes
Many Inherited Diseases Show One of Three Major
Patterns of Inheritance
DNA
Human Mutations
Linkage Studies Can Map Disease Genes with a
Resolution of About
Further Analysis Is Needed to Locate a Disease Gene
in Cloned
Many Inherited Diseases Result from Multiple Genetic
Defects
HQ Inactivating the Function of
Specific Genes in Eukaryotes
Normal Yeast Genes Can Be Replaced with Mutant
Alíeles
Transcription of Genes
Promoter Can Be Controlled Experimentally
Specific Genes Can Be Permanently Inactivated in
the Germ Line of Mice
Somatic Cell Recombination Can Inactivate Genes
in Specific Tissues
Dominant-Negative
Inhibit Some Genes
RNA
Destroying the Corresponding mRNA
6
CHROMOSOMES
Eukaryotic Gene Structure
217
Most Eukaryotic Genes Contain
mRNAs Encoding Single Proteins
Simple and Complex Transcription Units
Are Found in Eukaryotic Genomes
Protein-Coding Genes May Be Solitary or Belong
to a Gene Family
Heavily Used Gene Products Are Encoded by Multiple
Copies of Genes
Nonprotein-Coding Genes Encode Functional
RNAs
^2al Chromosomal Organization
of Genes and Noncoding
Genomes of Many Organisms Contain Much
Nonfunctional
Most Simple-Sequence DNAs Are Concentrated
in Specific Chromosomal Locations
DNA
in Length of Simple-Sequence DNAs
Unclassified Spacer
Portion of the Genome
(•Щ
Elements
Movement of Mobile Elements Involves a
DNA
DNA
and Eukaryotes
LTR Retrotransposons Behave Like Intracellular
Retroviruses
Non-LTR Retrotransposons Transpose by a Distinct
Mechanism
Other
DNA 234
Mobile
Evolution
ЦІ
Mitochondria Contain Multiple mtDNA Molecules
mtDNA Is Inherited Cytoplasmically
The Size, Structure, and Coding Capacity of mtDNA
Vary Considerably Between Organisms
Products of Mitochondrial Genes Are Not Exported
Mitochondria Evolved from a Single Endosymbiotic
Event Involving a
Mitochondrial Genetic Codes Differ from the
Standard Nuclear Code
Mutations in Mitochondrial
Genetic Diseases in Humans
Chloroplasts Contain Large DNAs Often Encoding
More Than a Hundred Proteins
Q3 Genomics: Genome-wide Analysis
of Gene Structure and Expression
Stored Sequences Suggest Functions of Newly
Identified Genes and Proteins
CONTENTS
XIX
Comparison of Related Sequences from Different
Species Can Give Clues to Evolutionary
Relationships Among Proteins
Genes Can Be Identified Within Genomic
Sequences
The Number of Protein-Coding Genes in an
Organism's Genome Is Not Directly Related
to Its Biological Complexity
Single Nucleotide Polymorphisms and Gene Copy-
Number Variation Are Important Determinants
of Differences Between Individuals of a Species
Structural Organization
of Eukaryotic Chromosomes
244
244
245
246
247
248
Chromatin Exists in Extended and Condensed Forms
Modifications of Histone Tails Control Chromatin
Condensation and Function
Nonhistone Proteins Provide a Structural Scaffold
for Long Chromatin Loops
Additional Nonhistone Proteins Regulate
Transcription and Replication
Small Molecules Regulate Expression of Many
Bacterial Genes via DNA-Binding Repressors
and Activators
Transcription Initiation from Some Promoters
Requires Alternative Sigma Factors
Transcription by aS4-RNA Polymerase Is Controlled
by Activators That Bind Far from the Promoter
Many Bacterial Responses Are Controlled by
Two-Component Regulatory Systems
EQI Overview of Eukaryotic Gene
Control and
Regulatory Elements in Eukaryotic
Both Close to and Many
Transcription Start Sites
Three Eukaryotic Polymerases Catalyze Formation
of Different RNAs
The Largest
Essential Carboxyl-Terminal Repeat
RNA
Sequences Corresponding to the
|эдЦ
of Eukaryotic Chromosomes
Chromosome Number, Size, and Shape at Metaphase
Are Species-Specific
During Metaphase, Chromosomes Can Be
Distinguished by Banding Patterns and
Chromosome Painting
Chromosome Painting and
the Evolution of Chromosomes
Interphase Polytene
Amplification
Three Functional Elements Are Required for Replication
and Stable Inheritance of Chromosomes
Centromere Sequences Vary Greatly in Length
Addition of Telomeric Sequences by Telomerase
Prevents Shortening of Chromosomes
TRANSCRIPTIONAL CONTROL
OF GENE EXPRESSION
269
Control of Gene Expression in
Bacteria
Transcription Initiation by Bacterial
Requires Association with a Sigma Factor
Initiation of lac Operon Transcription Can Be
Repressed and Activated
271
271
271
Цц|
Coding Genes
The TATA Box, Initiators, and CpG Islands Function
as Promoters in Eukaryotic
Promoter-Proximal Elements Help Regulate
Eukaryotic Genes
Distant Enhancers Often Stimulate Transcription
by
Most Eukaryotic Genes Are Regulated by Multiple
Transcription-Control Elements
Activators and Repressors of
Transcription
263
Interactions
Activators Are Modular Proteins Composed
of Distinct Functional Domains and Promote
Transcription
Repressors Inhibit Transcription and Are the
Functional Converse of Activators
DNA-Binding Domains Can Be Classified into
Numerous Structural Types
Structurally Diverse Activation and Repression
Domains Regulate Transcription
Transcription Factor Interactions Increase
Gene-Control Options
Multiprotein Complexes Form on Enhancers
282
282
282
284
285
286
286
288
290
290
293
294
295
xx
CONTENTS
Transcription Initiation
Polymerase II
296
General Transcription
Polymerase II
Sequential Assembly of Proteins Forms the Pol II
Transcription Preinitiation Complex in Vitro
In Vivo Transcription Initiation by Pol II Requires
Additional Proteins
Mitochondrial and
Transcribed by Organelle-Specific
Polymerases
317
8
CONTROL
Molecular Mechanisms of Transcription
Repression and Activation
Formation of Heterochromatin Silences Gene
Expression at Telomeres, Near Centromeres,
and in Other Regions
Repressors Can Direct Histone Deacetylation and
Methylation at Specific Genes
Activators Can Direct Histone Acetylation and
Methylation at Specific Genes
Chromatin-Remodeling Factors Help Activate or
Repress Transcription
299
299
303
305
306
Histone Modifications Vary Greatly in Their Stabilities
The Mediator Complex Forms a Molecular Bridge
Between Activation Domains and Pol II
307
Transcription of Many Genes Requires Ordered Binding
and Function of Activators and Co-activators
The Yeast Two-Hybrid System Exploits Activator Flexibility
to Detect cDNAs That Encode Interacting Proteins
Regulation of Transcription-Factor
Activity
Ali
Structure
312
Nuclear-Receptor Response Elements Contain Inverted
or Direct Repeats
Hormone Binding to a Nuclear Receptor Regulates Its
Activity as a Transcription Factor
Regulated Elongation and
Termination of Transcription
Transcription of the
an Antitermination Mechanism
Promoter-Proximal Pausing of
Occurs in Some Rapidly Induced Genes
Other Eukaryotic Transcription
Systems
Transcription Initiation by Pol I and Pol HI Is
Analogous to That by Pol II
313
314
315
316
316
316
Processing of Eukaryotic Pre-mRNA
The
Transcription Initiation
A Diverse Set of Proteins with Conserved RNA-Binding
Domains Associate with Pre-mRNAs
Splicing Occurs at Short, Conserved Sequences in
Pre-mRNAs via Two Transesterification Reactions
During Splicing, snRNAs Base-Pair with Pre-mRNA
Spliceosomes, Assembled from snRNPs and a
Pre-mRNA, Carry Out Splicing
Chain Elongation by
to the Presence of RNA-Processing Factors
SR Proteins Contribute to Exon Definition in Long
Pre-mRNAs
Self-Splicing Group II
Evolution of snRNAs
3'
Are Tightly Coupled
Nuclear Exonucleases Degrade
Out of Pre-mRNAs
Ц2Л
Processing
Alternative Splicing Is the Primary Mechanism for
Regulating mRNA Processing
A Cascade of Regulated
Drosophila
Splicing Repressors and Activators Control Splicing
at Alternative Sites
RNA
Some Pre-mRNAs
£Q Transport of mRNA Across the
Nuclear Envelope
Nuclear Pore Complexes Control Import and Export
from the Nucleus
Pre-mRNAs in Spliceosomes Are Not Exported from
the Nucleus
HłV
Viral mRNAs
CONTENTS
XXI
Cytoplasmic
transcriptional Control
Micro RNAs Repress Translation of Specific mRNAs
RNA
Complementary mRNAs
Cytoplasmic Polyadenylation Promotes Translation
of Some mRNAs
Degradation of mRNAs in the Cytoplasm Occurs
by Several Mechanisms
Protein Synthesis Can Be Globally Regulated
Sequence-Specific RNA-Binding Proteins Control
Specific mRNA Translation
Surveillance Mechanisms Prevent Translation of
Improperly Processed mRNAs
Localization of mRNAs Permits Production of
Proteins at Specific Regions Within the
Cytoplasm
jjjjf Processing of rRNA and tRNA
Pre-rRNA Genes Function as Nucleolar Organizers
and Are Similar in All Eukaryotes
Small Nucleolar RNAs Assist in Processing Pre-rRNAs
Self-Splicing Group I
Examples of Catalytic
Pre-tRNAs Undergo Extensive Modification in the
Nucleus
Nuclear Bodies Are Functionally Specialized Nuclear
Domains
Part III Cell Structure and Function
VISUALIZING, FRACTIONATING,
AND CULTURING CELLS
Organelies
The Plasma Membrane Has Many Common Functions
in All Cells
Endosomes Take Up Soluble Macromolecules from
the Cell Exterior
Lysosomes Are Acidic
Battery of Degradative Enzymes
Peroxisomes Degrade Fatty Acids and Toxic Compounds
The Endoplasmic Reticulum Is a Network of
Interconnected Internal Membranes
The Golgi Complex Processes and Sorts Secreted
and Membrane Proteins
Plant
Cell to Elongate Rapidly
The Nucleus Contains the
Synthetic Apparatus, and a Fibrous Matrix
Mitochondria Are the Principal Sites of ATP
Production in Aerobic Nonphotosynthetic Cells
Chloroplasts Contain Internal Compartments in
Which Photosynthesis Takes Place
Light Microscopy: Visualizing Cell
Structure and Localizing Proteins
Within Cells
The Resolution of the Light Microscope Is About
0.2
381
Phase-Contrast and Differential Interference Contrast
Microscopy Visualize Unstained Living Cells
Fluorescence Microscopy Can Localize and Quantify
Specific Molecules in Live Cells
Imaging Subcellular Details Often Requires that the
Samples Be Fixed, Sectioned, and Stained
Immunofluorescence Microscopy Can Detect Specific
Proteins in Fixed Cells
Confocal and Deconvolution Microscopy Enable
Visualization of Three-Dimensional Objects
Graphics and Informatics Have Transformed
Modern Microscopy
Qfl Electron Microscopy: Methods
and Applications
Resolution of Transmission Electron Microscopy is
Vastly Greater Than That of Light Microscopy
Cryoelectron Microscopy Allows Visualization of
Particles Without Fixation or Staining
Electron Microscopy of Metal-Coated Specimens
Can Reveal Surface Features of Cells and Their
Components
Purification of Cell
Disruption of Cells Releases Their Organelles
and Other Contents
Centrifugation Can Separate Many Types of
Organelles
Organelle-Specific Antibodies Are Useful in
Preparing Highly Purified Organelles
xx»
CONTENTS
gşm
of Metazoan Cells
Flow Cytometry Separates Different Cell Types
Culture of Animal Cells Requires Nutrient-Rich
Media and Special Solid Surfaces
Primary Cell Cultures Can Be Used to Study Cell
Differentiation
Primary Cell Cultures and Cell Strains Have a Finite
Life Span
Transformed Cells Can Grow Indefinitely in Culture
Some Cell Lines Undergo Differentiation in Culture
Hybrid Cells Called
Monoclonal Antibodies
HAT Medium Is Commonly Used to Isolate
Hybrid Cells
Classic Experiment
10
409
Lipid-Binding Motifs Help Target Peripheral
Proteins to the Membrane
Proteins Can Be Removed from Membranes
by Detergents or High-Salt Solutions
QQ| Phospholipids, Sphingolipids,
and Cholesterol: Synthesis
and Intracellular Movement
Fatty Acids Synthesis Is Mediated by Several
Important Enzymes
Small Cytosolic Proteins Facilitate Movement of
Fatty Acids
Incorporation of Fatty Acids into Membrane Lipids
Takes Place on
Flippases Move Phospholipids from One Membrane
Leaflet to the Opposite Leaflet
Cholesterol Is Synthesized by Enzymes in the Cytosol
and
Cholesterol and Phospholipids Are Transported
Between
ШШ
and
Phospholipids Spontaneously Form Bilayers
Phospholipid Bilayers Form a Sealed Compartment
Surrounding an Internal Aqueous Space
Biomembranes
of Lipids
Most Lipids and Many Proteins Are Laterally Mobile
in
Lipid
Properties of Membranes
Lipid
and Cytosolic Leaflets
Cholesterol and Sphingolipids Cluster with Specific
Proteins in Membrane
Biomembranes:
and Basic Functions
Proteins Interact with Membranes in Three
Different Ways
Most
Membrane-Spanning
Multiple
Membrane-Spanning "Barrels"
Covalently Attached Hydrocarbon Chains Anchor
Some Proteins to Membranes
All
Asymmetrically Oriented in the Bilayer
11
OF IONS AND SMALL MOLECULES
Overview of Membrane
Transport
Only Small
by Simple Diffusion
Membrane Proteins Mediate Transport of
Most Molecules and All Ions Across
Biomembranes
Uniport Transport of Glucose
and Water
Several Features Distinguish Uniport Transport from
Simple Diffusion
GLUT1 Uniporter Transports Glucose into Most
Mammalian Cells
The Human Genome Encodes a Family of Sugar-
Transporting GLUT Proteins
Transport Proteins Can Be Enriched Within Artificial
Membranes and Cells
Osmotic Pressure Causes Water to Move Across
Membranes
Aquaporins Increase the Water Permeability of Cell
Membranes
CONTENTS
XXIII
ATP-Powered Pumps and the
Intracellular lonk Environment
Different Classes of Pumps
Structural and Functional Properties
ATP-Powered Ion Pumps Generate and
Maintain Ionic Gradients Across Cellular
Membranes
Muscle Relaxation Depends on Ca2+ ATPases That
Pump Ca2+ from the Cytosol into the
Sarcoplasmk Reticulum
Calmodulin Regulates the Plasma Membrane
Ca2+ Pumps That Control Cytosolic Ca2"1"
Concentrations
Na+/K+ ATPase Maintains the Intracellular Na+
and K+ Concentrations in Animal Cells
V-Class H+ ATPases Maintain the Acidity of
Lysosomes and
Bacterial Permeases Are ABC Proteins That
Import a Variety of Nutrients from the
Environment
The Approximately
Play Diverse and Important Roles in Cell and
Organ Physiology
Certain ABC Proteins "Flip" Phospholipids
and Other Lipid-Soluble Substrates from
One Membrane Leaflet to the Opposite
Leaflet
Bacterial Symporter Structure Reveals the
Mechanism of Substrate Binding
Na+-Linked Ca2+ Antiporter Exports Ca2+ from
Cardiac Muscle Cells
Several Cotransporters Regulate
Cytosolic
A Putative Cation Exchange Protein Plays a
Key Role in Evolution of Human Skin
Pigmentation
Numerous Transport Proteins Enable Plant
Vacuoles
Transepithelial Transport
Multiple Transport Proteins Are Needed to
Move Glucose and
Epithelia
Simple Rehydration Therapy Depends on the
Osmotic Gradient Created by Absorption
of Glucose and Na+
Parietal Cells Acidify the Stomach Contents While
Maintaining a Neutral Cytosolic
Classic Experiment
Active Transport
12
479
Nongated Ion Channels and the
Resting Membrane Potential
Selective Movement of Ions Creates a
Transmembrane
Difference
The Membrane Potential in Animal Cells Depends
Largely on Potassium Ion Movements Through
Open Resting K+ Channels
Ion Channels Contain a Selectivity Filter Formed
from Conserved
Patch Clamps Permit Measurement of Ion
Movements Through Single Channels
Novel Ion Channels Can Be Characterized by a
Combination of Oocyte Expression and
Patch Clamping
Na+ Entry into Mammalian Cells Has a Negative
Change in Free Energy
Cotransport by Symporters and
Antiporters
Na+-Linked Symporters Import
Glucose into Animal Cells Against High
Concentration Gradients
First Steps of Glucose and Fatty
Acid Catabolism: Glycolysis
and the Citric Acid Cycle
During Glycolysis (Stage I), Cytosolic Enzymes
Convert Glucose to Pyruvate
The Rate of Glycolysis Is Adjusted to Meet
the Cell's Need for ATP
Glucose Is Fermented Under Anaerobic Conditions
Under Aerobic Conditions, Mitochondria
Efficiently Oxidize Pyruvate and Generate
ATP (Stages II-IV)
Mitochondria Are Dynamic
Structurally and Functionally Distinct Membranes
In Stage II, Pyruvate Is Oxidized to CO2 and High-
Energy Electrons Stored in Reduced Coenzymes
Transporters in the Inner Mitochondrial Membrane
Help Maintain Appropriate Cytosolic and Matrix
Concentrations of NAD+ and NADH
Mitochondrial Oxidation of Fatty Acids Generates
ATP
Peroxisomal Oxidation of Fatty Acids Generates
No ATP
480
481
483
485
485
485
487
489
491
491
xxiv
CONTENTS
The Electron Transport Chain and
Generation of the Proton-Motive
Force
Stepwise Electron Transport Efficiently Releases the
Energy Stored in NADH and FADH2
Electron Transport in Mitochondria Is Coupled to
Proton Pumping
Electrons Flow from FADH2 and NADH to O2
Through Four Multiprotein Complexes
Reduction Potentials of Electron Carriers Favor
Electron Flow from NADH to O2
Experiments Using Purified Complexes Established
the Stoichiometry of Proton Pumping
The
Translocated as Electrons Flow Through
Complex III
The Proton-Motive Force in Mitochondria Is Due
Largely to a Voltage Gradient Across the Inner
Membrane
Toxic By-products of Electron Transport Can
Damage Cells
ЦЮІ
Force for Energy-Requiring
Processes
The Mechanism of ATP Synthesis Is Shared
Among Bacteria, Mitochondria, and Chloroplasts
ATP Synthase Comprises Two Multiprotein
Complexes Termed Fo and F1
Rotation of the F,
Proton Movement Through Fo, Powers
ATP Synthesis
ATP-ADP Exchange Across the Inner Mitochondrial
Membrane Is Powered by the Proton-Motive
Force
Rate of Mitochondrial Oxidation Normally Depends
on ADP Levels
Brown-Fat Mitochondria Use the Proton-Motive
Force to Generate Heat
Photosynthesis and Light-Absorbing
Pigments
Thylakoid Membranes in Chloroplasts Are the Sites
of Photosynthesis in Plants
Three of the Four Stages in Photosynthesis Occur
Only During Illumination
Each Photon of Light Has a Defined Amount
of Energy
Photosystems
Associated Light-Harvesting Complexes
511
511
511
513
5Î4
Photoelectron Transport from Energized Reaction-
Center Chlorophyll a Produces a Charge
Separation
Internal Antenna and Light-Harvesting
Complexes Increase the Efficiency of
Photosynthesis
ЮЭ
Photosystems 517
The Single
Generates a Proton-Motive Force but No O2
Linear Electron Flow Through Both Plant
PSII and
O2, and NADPH
An Oxygen-Evolving Complex Is Located on
the
Center
Cells Use Multiple Mechanisms to Protect Against
Damage from Reactive Oxygen Species During
Photoelectron
Cyclic Electron Flow Through
Proton-Motive Force but No NADPH or O2
Relative Activities of
Regulated
ЮЗ
Photosynthesis
Rubisco Fixes CO2 in the Chloroplast
Synthesis of Sucrose Using Fixed CO2 Is Completed
in the Cytosol
Light and Rubisco
Fixation
Photorespiration,
Photosynthesis, Is Reduced in Plants That Fix
CO2 by the C4 Pathway
13
MEMBRANES AND ORGANELLES
Translocation
Across the
A
Nascent Secretory Proteins to the
Cotransiational
GTP-Hydrolyzing Proteins
Passage of Growing Polypeptides Through the
Translocon Is Driven by Energy Released During
Translation
CONTENTS
XXV
ATP Hydrolysis Powers Post-translational
Translocation
Insertion of Proteins into the
ER
Several Topological Classes of Integral Membrane
Proteins Are Synthesized on the
Internal Stop-Transfer and Signal-Anchor Sequences
Determine Topology of Single-Pass Proteins
Multipass Proteins Have Multiple Internal
Topogenic Sequences
A Phospholipid Anchor Tethers Some Cell-Surface
Proteins to the Membrane
The Topology of a Membrane Protein Often Can
Be Deduced from Its Sequence
Protein Modifications, Folding,
and Quality Control in the
A Preformed W-Linked Oligosaccharide Is Added to
Many Proteins in the Rough
Oligosaccharide Side Chains May Promote Folding
and Stability of Glycoproteins
Disulfide Bonds Are Formed and Rearranged by
Proteins in the
Chaperones and Other
and Assembly of Proteins
Improperly Folded Proteins in the
Expression of Protein-Folding Catalysts
Unassembled or Misfolded Proteins in the
Often Transported to the Cytosol for
Degradation
Sorting of Proteins to Mitochondria
and Chloroplasts
Amphipathic N-Terminal Signal Sequences Direct
Proteins to the Mitochondrial Matrix
558
Mitochondrial Protein Import Requires Outer-Membrane
Receptors and Translocons in Both Membranes
Studies with Chimeric Proteins Demonstrate Important
Features of Mitochondrial Import
Three Energy Inputs Are Needed to Import Proteins
into Mitochondria
Multiple Signals and Pathways Target Proteins to
Submitochondrial Compartments
Targeting of Chloroplast Stromal Proteins Is Similar to
Import of Mitochondrial Matrix Proteins
Proteins Are Targeted to Thylakoids by Mechanisms
Related to
Inner Membrane
Sorting of Peroxisomal Proteins
Cytosolic Receptor Targets Proteins with an SKL
Sequence at the C-Terminus into the Peroxisomal
Matrix
Peroxisomal Membrane and Matrix Proteins Are
Incorporated by Different Pathways
Transport into and out of the
Nucleus
Large and Small Molecules Enter and Leave the
Nucleus via Nuclear Pore Complexes
Importins Transport Proteins Containing Nuclear-
Localization Signals into the Nucleus
Exportins Transport Proteins Containing Nuclear-Export
Signals out of the Nucleus
Most mRNAs Are Exported from the Nucleus by a
Ran-lndependent Mechanism
14
AND ENDOCYTOSIS
Techniques for Studying the
Secretory Pathway
Transport of a Protein Through the Secretory
Pathway Can Be Assayed in Living Cells
Yeast Mutants Define Major Stages and Many
Components in Vesicular Transport
Cell-Free Transport Assays Allow Dissection of
Individual Steps in Vesicular Transport
Molecular Mechanisms of
Vesicular Traffic
Assembly of a Protein Coat Drives Vesicle
Formation and Selection of Cargo
Molecules
A Conserved Set of GTPase Switch Proteins Controls
Assembly of Different Vesicle Coats
Targeting Sequences on Cargo Proteins Make
Specific Molecular Contacts with Coat
Proteins
Rab
Membranes
Paired Sets of SNARE Proteins Mediate Fusion of
Vesicles with Target Membranes
Dissociation of SNARE Complexes After Membrane
Fusion Is Driven by ATP Hydrolysis
xxvi
CONTENTS
Early Stages of the Secretory
Pathway
592
COPII
to the Golgi
COPI Vesicles Mediate Retrograde Transport within
the Golgi and from the Golgi to the
Anterograde Transport Through the Golgi Occurs
by Cistemal Maturation
Later Stages of the Secretory
Pathway
Vesicles Coated with Clathrin and/or Adapter Proteins
Mediate Several Transport Steps
Dynamin Is Required for Pinching Off of Clathrin
Vesicles
Mannose 6-Phosphate Residues Target Soluble
Proteins to Lysosomes
Study of Lysosomal Storage Diseases Revealed Key
Components of the Lysosomal Sorting Pathway
Protein Aggregation in the frans-Golgi May Function
in Sorting Proteins to Regulated Secretory Vesicles
Some Proteins Undergo Proteolytic Processing
After Leaving the trans-Golgi
Several Pathways Sort Membrane Proteins to the
Apical or Basolateral Region of Polarized Cells
^QjU
Cells Take Up Lipids from the Blood in the Form of
Large, Weil-Defined Lipoprotein Complexes
Receptors for Low-Density Lipoprotein and Other
Ligands Contain Sorting Signals That Target
Them for Endocytosis
The Acidic
Receptor-Ligand Complexes to Dissociate
The Endocytic Pathway Delivers Iron to Cells without
Dissociation of the Receptor-Transferrin Complex
in Endosomes
Directing Membrane Proteins
and Cytosolic Materials to the
Lysosome
Multivesicular Endosomes Segregate Membrane
Proteins Destined for the Lysosomal
Membrane from Proteins Destined for
Lysosomal Degradation
Retroviruses Bud from the Plasma Membrane by a Process
Similar to Formation of Multivesicular Endosomes
15
TRANSDUCTION AND SHORT-TERM
CELLULAR RESPONSES
From Extracellular Signal to Cellular
Response
Signaling Cells Produce and Release Signaling
Molecules
Signaling Molecules Can Act Locally or at a Distance
Binding of Signaling Molecules Activates
Receptors on Target Cells
Щ5Щ
Receptors
Receptor Proteins Bind Ligands Specifically
The Dissociation Constant Is a Measure of the
Affinity of a Receptor for Its Ligand
Binding Assays Are Used to Detect Receptors and
Determine Their Affinities for Ligands
Maximal Cellular Response to a Signaling Molecule
Usually Does Not Require Activation of All
Receptors
Sensitivity of a Cell to External Signals Is Determined
by the Number of Surface Receptors and Their
Affinity for Ligand
Receptors Can Be Purified by Affinity Techniques
Classic Experiment
Out of the Cell
621
ЮЗ
of Intracellular Signal-Transduction
Pathways
GTP-Binding Proteins Are Frequently Used As On/Off
Switches
Protein Kinases and Phosphatases are Employed in
Virtually All Signaling Pathways
Second Messengers Carry and Amplify Signals from
Many Receptors
General Elements of
Coupled Receptor Systems
G
Family with a Common Structure and Function
G
GTP for GDP on the
Protein
Different
and in Turn Regulate Different Effector Proteins
CONTENTS
XXVII
щ^З
That Regulate Ion Channels
Acetylcholine Receptors in the Heart Muscle
Activate
Light Activates G^-Coupled Rhodopsins
Activation of Rhodopsin Induces Closing of
cGMP-Gated Cation Channels
Rod Cells Adapt to Varying Levels of Ambient Light
Because of Opsin Phosphorylation and Binding
of
Insulin and Glucagon Work Together to Maintain a
Stable Blood Glucose Level
658
Classic Experiment
Transduction—GTP Stimulation of cAMP Synthesis
16
PATHWAYS THAT CONTROL GENE
ACTIVITY
Ц22Я
Activate or Inhibit Adenylyl
Cyclase
Adenylyl Cyclase Is Stimulated and Inhibited
by Different Receptor-Ligand Complexes
Structural Studies Established How G^GTP Binds
to and Activates Adenylyl Cyclase
cAMP Activates Protein Kinase A by Releasing
Catalytic Subunits
Glycogen Metabolism Is Regulated by
Hormone-Induced Activation of Protein Kinase A
cAMP-Mediated Activation of Protein Kinase A
Produces Diverse Responses in Different Cell Types
Signal Amplification Commonly Occurs in Many
Signaling Pathways
Several Mechanisms Down-Regulate Signaling
from
Anchoring Proteins Localize Effects of cAMP to
Specific Regions of the Cell
QQI
Activate Phospholipase
Phosphorylated Derivatives of Inositol Are
Important Second Messengers
Calcium Ion Release from the
Reticulum is Triggered by IP3
The Ca2+/Calmodulin Complex Mediates Many
Cellular Responses to External Signals
Diacylglycerol (DAG) Activates Protein Kinase C,
Which Regulates Many Other Proteins
Signal-Induced Relaxation of Vascular Smooth
Muscle Is Mediated by cGMP-Activated
Protein Kinase
Integrating Responses of Cells
to Environmental Influences
Integration of Multiple Second Messengers Regulates
Glycogenolysis
TGFß
Activation of Smads
A
of an Inactive Precursor
Radioactive Tagging Was Used to Identify
Receptors
Activated
Transcription Factors
Negative Feedback Loops Regulate
Signaling
Loss of
in Cancer
Cytokine Receptors and the
JAK/STAT Pathway
Cytokines Influence Development of Many Cell
Types
Cytokine Receptors Have Similar Structures and
Activate Similar Signaling Pathways
JAK
Complementation Genetics Revealed That
JAK
Signals
Signaling from Cytokine Receptors Is Regulated
by Negative Signals
Mutant Erythropoietin Receptor That Cannot Be
Turned Off Leads to Increased Numbers of
Erythrocytes
Receptor Tyrosine Kinases
Ligand Binding Leads to Phosphorylation and
Activation of Intrinsic Kinase in RTKs
Overexpression of HER2, a Receptor
Tyrosine Kinase, Occurs in Some Breast
Cancers
XXVIII
CONTENTS
Conserved Domains Are Important for Binding Signal-
Transduction Proteins to Activated Receptors
Down-regulation of RTK Signaling Occurs by
Endocytosis and Lysosomal Degradation
Activation of
Pathways
Ras, a
and Inactive States
Receptor Tyrosine Kinases Are Linked to
Adapter Proteins
Genetic Studies in
Signal-Transducing Proteins in the Ras/MAP
Kinase Pathway
Binding of
Conformational Change That Activates
Signals Pass from Activated
Protein Kinases
MAP Kinase Regulates the Activity of Many Transcription
Factors Controlling Early-Response Genes
G
MAP Kinase in Yeast Mating Pathways
Scaffold Proteins Separate Multiple MAP Kinase
Pathways in Eukaryotic Cells
The Ras/MAP Kinase Pathway Can Induce Diverse
Cellular Responses
ЮЗ
Transducers
Phospholipase
Cytokine Receptors
Recruitment of PI-3 Kinase to Hormone-Stimulated
Receptors Leads to Synthesis of Phosphorylated
Phosphatidylinositols
Accumulation of PI 3-Phosphates in the Plasma
Membrane Leads to Activation of Several Kinases
Activated Protein Kinase
Cellular Responses
The PI-3 Kinase Pathway Is Negatively Regulated
by PTEN Phosphatase
Hedgehog Signaling Relieves Repression of Target
Genes
700
QQI Pathways That Involve Signal-Induced
Protein Cleavage
Degradation of an Inhibitor Protein Activates the
NF-kB Transcription Factors
Ligand-Activated Notch Is Cleaved Twice, Releasing
a Transcription Factor
Matrix Metalloproteases Catalyze Cleavage of Many
Signaling Proteins from the Cell Surface
Inappropriate Cleavage of Amyloid Precursor Protein
Can Lead to Alzheimer's Disease
Regulated Intramembrane Proteolysis of SREBP
Releases a Transcription Factor That Acts to
Maintain Phospholipid and Cholesterol Levels
17
MOVEMENT I:
Microfilaments
Structures
Actin Is Ancient, Abundant, and Highly Conserved
G-Actin Monomers Assemble into Long, Helical
F-Actin Polymers
F-Actin Has Structural and Functional Polarity
Dynamics of Actin Filaments
Actin Polymerization in Vitro Proceeds in Three Steps
Actin Filaments Grow Faster at
(-)
Actin Filament Treadmilling Is Accelerated by
Profilin
Thymosin-ß4
Polymerization
Capping Proteins Block Assembly and Disassembly
at Actin Filament Ends
720
721
722
722
Activation of Gene Transcription
by Seven-Spanning Cell-Surface
Receptors
CREB Links cAMP and Protein Kinase A to Activation
of Gene Transcription
GPCR-Bound Arrestin
Wnt Signals Trigger Release of a Transcription
Factor from Cytosolic Protein Complex
Mechanisms of Actin Filament
Assembly
Formins Assemble Unbranched Filaments
The Arp2/3 Complex Nucleates Branched Filament
Assembly
Intraceliular Movements Can Be Powered by Actin
Polymerization
CONTENTS
XXIX
Toxins That Perturb the Pool of Actin Monomers
Are Useful for Studying Actin Dynamics
726
Chemotactic Gradients Induce Altered Phosphoinositide
Levels Between the Front and Back of a Cell
Organization of Actin-Based Cellular
Structures
Cross-Linking Proteins Organize Actin Filaments into
Bundles or Networks
Adaptor Proteins Link Actin Filaments to
Membranes
Myosins: Actin-Based Motor
Proteins
Myosins Have Head, Neck, and Tail Domains with
Distinct Functions
Myosins Make Up a Large Family of
Mechanochemical Motor Proteins
Conformational Changes in the Myosin Head
Couple ATP Hydrolysis to Movement
Myosin Heads Take Discrete Steps Along
Actin Filaments
Myosin V Walks Hand Over Hand Down an Actin
Filament
Myosin-Powered Movements
Myosin Thick Filaments and Actin Thin Filaments
¡n Skeletal Muscle Slide Past One Another
During Contraction
Skeletal Muscle Is Structured by Stabilizing and
Scaffolding Proteins
Contraction of Skeletal Muscle Is Regulated by Ca2+
and Actin-Binding Proteins
Actin and Myosin II Form Contractile Bundles in
Nonmuscle Cells
Myosin-Dependent Mechanisms Regulate
Contraction in Smooth Muscle and Nonmuscle Cells
Myosin-V-Bound Vesicles Are Carried Along
Actin Filaments
Cell Migration: Signaling and
Chemotaxis
743
745
Cell Migration Coordinates Force Generation with
Cell Adhesion and Membrane Recycling
The Small GTP-Binding Proteins Cdc42,
Control Actin Organization
Cell Migration Involves the Coordinate Regulation
of Cdc42,
Migrating Cells Are Steered by Chemotactic
Molecules
Classic Experiment
Contraction
755
18
MOVEMENT II: MICROTUBULES
AND INTERMEDIATE FILAMENTS
Microtubule Structure and
Organization
Microtubule Walls Are Polarized Structures Built
from
Microtubules Are Assembled from MTOCs to
Generate Diverse Organizations
ЩЮЦ
Microtubules Are Dynamic Structures Due to
Kinetic Differences at Their Ends
Individual Microtubules Exhibit Dynamic Instability
Localized Assembly and "Search-and-Capture"
Help Organize Microtubules
Drugs Affecting Tubulin Polymerization Are Useful
Experimentally and to Treat Diseases
Regulation of Microtubule Structure
and Dynamics
Microtubules Are Stabilized by Side- and
End-Binding Proteins
Microtubules Are Disassembled by End Binding
and Severing Proteins
Kinesins and Dyneins: Microtubule-
Based Motor Proteins
Organelles in
Microtubules in Both Directions
Kinesin-1 Powers Anterograde Transport of
Vesicles Down
Microtubules
Kinesins Form a Large Protein Family with Diverse
Functions
Kinesin-1 Is a Highly
Dynein Motors Transport Organelles Toward the
End of Microtubules
Kinesins and Dyneins Cooperate in the Transport
of Organelles Throughout the Cell
xxx
CONTENTS
QQI Cilia
Based Surface Structures
Eukaryotic Cilia and
Microtubules Bridged by Dynein Motors
Ciliary and
Controlled Sliding of Outer Doublet
Microtubules
Intraflagellar Transport Moves Material Up and
Down Cilia and
Defects in Intraflagellar Transport Cause Disease
by Affecting Sensory Primary Cilia
ЦВДІ
Mitosis Can Be Divided into Six Phases
Centrosomes Duplicate Early in the Cell Cycle in
Preparation for Mitosis
The Mitotic Spindle Contains Three Classes of
Microtubules
Microtubule Dynamics Increases Dramatically
in Mitosis
Microtubules Treadmill During Mitosis
The Kinetochore Captures and Helps Transport
Chromosomes
Duplicated Chromosomes Are Aligned by Motors
and Treadmilling Microtubules
Anaphase
Microtubule Shortening
Anaphase
Action of Kinesins and Dynein
Additional Mechanisms Contribute to Spindle
Formation
Cytokinesis Splits the Duplicated Cell in Two
Plant Cells Reorganize Their Microtubules and
Build a New Cell Wall in Mitosis
ЦЦ2Л
Intermediate Filaments Are Assembled from
Subunit
Intermediate Filaments Proteins Are Expressed
in a Tissue-Specific Manner
Intermediate Filaments Are Dynamic
Defects in Lamins and Keratins Cause Many Diseases
Microfilaments
Transport Melanosomes
Cdc42 Coordinates Microtubules and
During Cell Migration
778
19
TISSUES
801
779
780
щущ
An Overview
803
Cell-Adhesion Molecules Bind to One Another and
781
to Intracellular Proteins
803
782
The Extracellular Matrix Participates in Adhesion,
Signaling, and Other Functions
805
783
The Evolution of Multifaceted Adhesion Molecules
Enabled the Evolution of Diverse Animal Tissues
807
784
ЦЦ
784
and Their Adhesion Molecules
808
785
Epithelial Cells Have Distinct Apical, Lateral, and
786
Basal Surfaces
808
Three Types of Junctions Mediate Many Cell-Cell
788
and Cell-ECM Interactions
809
Cadherins Mediate Cell-Cell Adhesions in Adherens
789
Junctions and Desmosomes
810
Tight Junctions Seal Off Body Cavities and Restrict
789
Diffusion of Membrane Components
814
Integrins
816
789
Gap Junctions Composed of Connexins Allow Small
789
Molecules to Pass Directly Between Adjacent Cells
817
Ц2Л
The Basal Lamina
The Basal Lamina Provides a Foundation for
Assembly of Cells into Tissues
Laminin, a Multiadhesive Matrix Protein, Helps
Cross-link Components of the Basal Lamina
Sheet-Forming Type IV Collagen Is a Major Structural
Component of the Basal Lamina
Perlecan, a Proteoglycan, Cross-links Components
of the Basal Lamina and Cell-Surface Receptors
Coordination and Cooperation
between Cytoskeletal Elements
Intermediate Filament-Associated Proteins
Contribute to Cellular Organization
ЕИ
Connective and Other Tissues
Fibrillar
in the ECM of Connective Tissues
CONTENTS
XXXI
Fibrillar
Fibrils Outside of the Cell
Type I and II
Collagens
Proteoglycans and Their Constituent GAGs Play
Diverse Roles in the ECM
Hyaluronan Resists Compression, Facilitates Cell Migration,
and Gives Cartilage Its Gel-like Properties
Fibronectins Interconnect Cells and Matrix, Influencing
Cell Shape, Differentiation, and Movement
Adhesive Interactions in Motile
and Nonmotile Cells
Integrins
Three-Dimensional Environment
Regulation of Integrin-Mediated Adhesion and
Signaling Controls Cell Movement
Connections Between the ECM and Cytoskeleton
Are Defective in Muscular Dystrophy
IgCAMs Mediate Cell-Cell Adhesion in
and Other Tissues
Leukocyte Movement into Tissues Is Orchestrated
by a Precisely Timed Sequence of Adhesive
Interactions
Plant Tissues
The Plant Cell Wall Is a Laminate of Cellulose Fibrils
in a Matrix of Glycoproteins
Loosening of the Cell Wall Permits Plant Cell
Growth
Plasmodesmata Directly Connect the Cytosols of
Adjacent Cells in Higher Plants
Only a Few Adhesive Molecules Have Been
Identified in Plants
Part IV Cell Growth and Development
20
CELL CYCLE
Overview of the Cell Cycle
and Its Control
The Cell Cycle Is an Ordered Series of Events
Leading to Cell Replication
Regulated Protein Phosphorylation and
Degradation Control Passage Through the
Cell Cycle
Diverse Experimental Systems Have Been Used to
Identify and Isolate Cell-Cycle Control Proteins
Control of Mitosis by Cyclins and
MPF Activity
Maturation-Promoting Factor (MPF) Stimulates
Meiotic Maturation in Oocytes and Mitosis
in Somatic Cells
Mitotic Cyclin Was First Identified in Early Sea
Urchin Embryos
Cyclin
Promoting Factor (MPF) Change Together in
Cycling Xenopus Egg Extracts
Anaphase-Promoting Complex (APC/C) Controls
Degradation of Mitotic Cyclins and Exit from
Mitosis
Cyclin-Dependent Kinase Regulation
During Mitosis
MPF Components Are Conserved Between Lower
and Higher Eukaryotes
Phosphorylation of the CDK
Kinase Activity of MPF
Conformational Changes Induced by Cyclin
Binding and Phosphorylation Increase
MPF Activity
Molecular Mechanisms for
Regulating Mitotic Events
Phosphorylation of Nuclear Lamins and Other
Proteins Promotes Early Mitotic Events
Unlinking of Sister Chromatids Initiates
Chromosome Decondensation and Reassembly of the
Nuclear Envelope Depend on Dephosphorylation
of MPF Substrates
Cyclin-CDK and Ubiquitin-Protein
Ligase
A Cyclin-Dependent Kinase (CDK) Is Critical for
S-Phase Entry in
Three
to Form S-Phase-Promoting Factors
xxxii
CONTENTS
Degradation
Replication
Multiple Cyclins Regulate the Kinase Activity of
S. cerevisiae CDK During Different Cell-Cycle Phases
Replication at Each Origin Is Initiated Only Once
During the Cell Cycle
gţjiBSfl
Cells
Mammalian Restriction Point Is Analogous to
START in Yeast Cells
Multiple CDKs and Cyclins Regulate Passage of
Mammalian Cells Through the Cell Cycle
Regulated Expression of Two Classes of Genes
Returns Go Mammalian Cells to the Cell Cycle
Passage Through the Restriction Point Depends on
Phosphorylation of the Tumor-Suppressor Rb Protein
Cyclin A Is Required for
for Entry into Mitosis
Two Types of Cyclin-CDK Inhibitors Contribute to
Cell-Cycle Control in Mammals
ЕШЛ
Regulation
The Presence of Unreplicated
into Mitosis
Improper Assembly of the Mitotic Spindle Prevents
the Initiation of
Proper Segregation of Daughter Chromosomes Is
Monitored by the Mitotic Exit Network
Cell-Cycle Arrest of Cells with Damaged
on Tumor Suppressors
ЩЦ
Division
892
892
Key Features Distinguish Meiosis from Mitosis
Repression of
Kinase Promote Premeiotic
Recombination and a Meiosis-Specific Cohesin
Are Necessary for the Specialized Chromosome
Segregation in Meiosis I
Special Properties of Rec8 Regulate Its Cleavage in
Meiosis I and II
The
Kinetochores in Meiosis I
Tension on Spindle Microtubules Contributes to
Proper Spindle Attachment
895
896
898
898
Classic Experiment
from the Sea: The Discovery of Cyclins
21
DEATH
The Birth of Cells: Stem Cells,
Niches, and Lineage
Stem Cells Give Rise to Both Stem Cells and
Differentiating Cells
Cell Fates Are Progressively Restricted During
Development
The Complete Cell Lineage of
Heterochronic Mutants Provide Clues About Control
of Cell Lineage
Cultured Embryonic Stem Cells Can Differentiate into
Various Cell Types
Adult Stem Cells for Different Animal Tissues Occupy
Sustaining Niches
Meristems Are
Plants
ЩЩ
Mating-Type Transcription Factors Specify
Cell Types
MCM1 and
Transcription
аг-МСМІ
Pheromones Induce Mating of
Generate a Third Cell Type
Specification and Differentiation
of Muscle
Embryonic Somites Give Rise to Myoblasts
Myogenic Genes Were First Identified in Studies with
Cultured
Two Classes of Regulatory Factors Act in Concert to
Guide Production of Muscle Cells
Differentiation of Myoblasts Is Under Positive and
Negative Control
Cell-Cell Signals Are Crucial for Determination and
Migration of Myoblasts
bHLH Regulatory Proteins Function in Creation of
Other Tissues
Regulation of Asymmetric
Cell Division
Yeast Mating-Type Switching Depends upon
Asymmetric Cell Division
CONTENTS
XXXIII
Proteins
Opposite Ends of Dividing Neuroblasts in
Cell Death and Its Regulation
Programmed Cell Death Occurs Through Apoptosis
Neurotrophins Promote Survival of Neurons
A Cascade of Caspase Proteins Functions in One
Apoptotic Pathway
Pro-Apoptotic Regulators Permit Caspase Activation
in the Absence of Trophic Factors
Some Trophic Factors Induce Inactivation of
a Pro-Apoptotic Regulator
Tumor Necrosis Factor and Related Death Signals
Promote Cell Murder by Activating Caspases
22
OF DEVELOPMENT
Highlights of Development
(ЩЩ
Germ-line Cells Are All That We Inherit
Fertilization Unifies the Genome
Genomic Imprinting Controls Gene Activation
According to Maternal or Paternal Chromosome
Origin
Too Much of a Good Thing: The X Chromosome Is
Regulated by Dosage Compensation
in Early Vertebrate Embryos
Cleavage Leads to the First Differentiation Events
The Genomes of Most Somatic Cells Are Complete
Gastrulation Creates Multiple Tissue Layers, Which
Become Polarized
Signal Gradients May Induce Different Cell Fates
Signal Antagonists Influence Cell Fates and Tissue
Induction
A Cascade of Signals Distinguishes Left from Right
950
Development Progresses from Egg and Sperm
to an Early Embryo
As the Embryo Develops, Cell Layers Become Tissues
and Organs
Genes That Regulate Development Are at the
Heart of Evolution
952
953
953
955
958
958
959
960
961
961
963
965
966
Control of Body Segmentation:
Themes and Variations in Insects
and Vertebrates
Early
Transcriptional Control Specifies the Embryo's
Anterior and Posterior
Translation Inhibitors Reinforce Anterior-Posterior
Patterning
Insect Segmentation Is Controlled by a Cascade
of Transcription Factors
Vertebrate Segmentation Is Controlled by Cyclical
Expression of Regulatory Genes
Differences Between Segments Are Controlled by
Hox Genes
Hox-Gene Expression Is Maintained by a Variety
of Mechanisms
Flower Development Requires Spatially Regulated
Production of Transcription Factors
Cell-Type Specification in Early
Neural Development
Neurulation Begins Formation of the Brain and
Spinal Cord
Signal Gradients and Transcription Factors Specify Cell
Types in the Neural Tube and Somites
Most Neurons in the Brain Arise in the Innermost
Neural Tube and Migrate Outward
Lateral Inhibition Mediated by Notch Signaling
Causes Early Neural Cells to Become Different
Growth and Patterning of Limbs
Hox Genes Determine the Right Places for
Limbs to Grow
Limb Development Depends on Integration
of Multiple Extracellular Signal Gradients
Hox Genes Also Control Fine Patterning
of Limb Structures
So Far, So Good
Classic Experiment
Mutations to Study Development
990
991
992
994
999
23
949
Neurons and
Blocks of the Nervous System
Information Flows Through Neurons from
to
xxxiv
CONTENTS
Information Moves as Pulses of Ion Flow Called
Action Potentials
Information Flows Between Neurons via
Synapses
The Nervous System Uses Signaling Circuits
Composed of Multiple Neurons
Q29 Voltage-Gated Ion Channels
and the Propagation of Action
Potentials in Nerve Cells
The Magnitude of the Action Potential Is Close
to £Na
Sequential Opening and Closing of Voltage-
Gated Na+ and K+ Channels Generate Action
Potentials
Action Potentials Are Propagated Unidirectionally
Without Diminution
Nerve Cells Can Conduct Many Action Potentials
in the Absence of ATP
All Voltage-Gated Ion Channels Have Similar
Structures
Voltage-Sensing S4
to Membrane Depolarization
Movement of the Channel-Inactivating Segment
into the Open Pore Blocks Ion Flow
Myelination Increases the Velocity of Impulse
Conduction
Action Potentials "Jump" from Node to Node
in Myelinated
Glia
QQI Communication at Synapses
Formation of Synapses Requires Assembly of
Presynaptic and Postsynaptic Structures
Neurotransmitters
Vesicles by H^Linked Antiport Proteins
Synaptic Vesicles Loaded with
Are Localized near the Plasma Membrane
Influx of Ca2+ Triggers Release of
Neurotransmitters
A Calcium-Binding Protein Regulates Fusion of
Synaptic Vesicles with the Plasma Membrane
Signaling at Synapses Is Terminated by Degradation
or Reuptake of
Fly Mutants Lacking Dynamin Cannot Recycle
Synaptic Vesicles
Opening of Acetylcholine-Gated Cation Channels
Leads to Muscle Contraction
All Five Subunits in the Nicotinic Acetylcholine
Receptor Contribute to the Ion Channel
Nerve Cells Make an All-or-None Decision to
Generate an Action Potential
Gap Junctions Also Allow Neurons to Communicate
ЕЭД
Hearing, Tasting, and Smelling
The Eye Features Light-Sensitive Nerve Cells
Eyes Reflect Evolutionary History
Integrated Information from Multiple Ganglion
Cells Forms Images of the World
Mechanosensory Cells Detect Pain, Heat, Cold,
Touch, and Pressure
Inner Ear Cells Detect Sound and Motion
Five Primary Tastes Are Sensed by Subsets of Cells
in Each Taste Bud
A Plethora of Receptors Detect Odors
The Path to Success: Controlling
Axon Growth and Targeting
The Growth Cone Is a Motorized Sensory
Guidance Structure
The Retinotectal Map Revealed an Ordered
System of Axon Connections
There Are Four Families of Axon Guidance
Molecules
Developmental Regulators Also Guide
Axon Guidance Molecules Cause the Growth
Cone to Turn
24
1055
ОЛ
Pathogens Enter the Body Through Different
Routes and Replicate at Different Sites
Leukocytes Circulate Throughout the Body and
Take Up Residence in Tissues and Lymph Nodes
Mechanical and Chemical Boundaries Form
a First Layer of Defense Against Pathogens
Innate Immunity Provides a Second Line
of Defense After Mechanical and Chemical
Barriers Are Crossed
Inflammation Is a Complex Response to Injury That
Encompasses Both Innate and Adaptive Immunity
Adaptive Immunity, the Third Line of Defense,
Exhibits Specificity
CONTENTS
XXXV
QQI Immunoglobulins:
and Function
Immunoglobulins Have a Conserved Structure
Consisting of Heavy and Light Chains
Multiple Immunoglobulin
Each with Different Functions
Each
Immunoglobulin
Immunoglobulin Domains Have a Characteristic Fold
Composed of Two
by a Disulfide Bond
The Three-Dimensional Structure of Antibody
Molecules Accounts for Their Exquisite
Specificity
An Immunoglobulin's Constant Region Determines Its
Functional Properties
Generation of Antibody Diversity
and B-Cell Development
A Functional Light-Chain Gene Requires Assembly
of V and
Rearrangement of the Heavy-Chain Locus Involves
V, D, and
Somatic Hypermutation Allows the Generation
and Selection of Antibodies with Improved
Affinities
B-Cell Development Requires Input from a
Pre-B Cell Receptor
During an Adaptive Response,
from Making Membrane-Bound
Secreted
В
They Make
The MHC and Antigen
Presentation
The MHC Determines the Ability of Two Unrelated
Individuals of the Same Species
to Accept or Reject Grafts
The Killing Activity of Cytotoxic
Specific and MHC Restricted
T
Guided by Two Distinct Classes of MHC Molecules
MHC Molecules Bind
and Interact with the
Antigen Presentation Is the Process by Which
Protein Fragments Are Complexed with MHC
Products and Posted to the Cell Surface
Class I MHC Pathway Presents Cytosolic Antigens
Class II MHC Pathway Presents Antigens Delivered
to the Endocytic Pathway
1082
1082
1084
T
and
The Structure of the
the F(ab) Portion of an Immunoglobulin
TCR Genes Are Rearranged in a Manner Similar to
Immunoglobulin Genes
Т
of Their Variable Residues Encoded in the
Junctions between V, D, and
Signaling via Antigen-Specific Receptors Triggers
Proliferation and Differentiation
of
T
Develop Through a Process of Positive
and Negative Selection
T
for Full Activation
Cytotoxic
and Are Specialized for Killing
T
Signals to Other Immune Cells
CD4
Based on Their Cytokine Production
and Expression of Surface Markers
Leukocytes Move in Response to Chemotactic Cues
Provided by Chemokines
Collaboration of Immune-System
Cells in the Adaptive Response
Toll-Like Receptors Perceive a Variety
of Pathogen-Derived Macromolecular Patterns
Engagement of Toll-Like Receptors Leads
to Activation of Antigen-Presenting Cells
Production of High-Affinity Antibodies Requires
Collaboration Between
Vaccines Elicit Protective Immunity Against
a Variety of Pathogens
Classic Experiment
Somatic Rearrangement of Immunoglobulin Genes
25
1107
Tumor Cells and the Onset
of Cancer
1109
Metastatic Tumor Cells Are Invasive and Can Spread
Cancers Usually Originate in Proliferating Cells
Cancer Stem Cells Can Be a Minority Population
Tumor Growth Requires Formation of
New Blood Vessels
1111
xxxvi
CONTENTS
Specific
into Tumor Cells
A Multi-hit Model of Cancer Induction Is Supported
by Several Lines of Evidence
Successive Oncogenic Mutations Can Be Traced
in Colon Cancers
DNA Microarray
Reveal Subtle Differences Between Tumor Cells
££2Ш
Gain-of-Function Mutations Convert Proto-oncogenes
into Oncogenes
Cancer-Causing Viruses Contain Oncogenes or
Activate Cellular Proto-oncogenes
Loss-of-Function Mutations in Tumor-Suppressor
Genes Are Oncogenic
Inherited Mutations in Tumor-Suppressor Genes
Increase Cancer Risk
Aberrations in Signaling Pathways That Control
Development Are Associated with Many Cancers
^Ц£|
Promoting Proteins
Oncogenic Receptors Can Promote Proliferation in
the Absence of External Growth Factors
Viral Activators of Growth-Factor Receptors Act
as Oncoproteins
Many Oncogenes Encode Constitutively Active
Signal-Transduction Proteins
Inappropriate Production of Nuclear Transcription
Factors Can Induce Transformation
Molecular Cell Biology Is Changing How Cancer
Is Treated
О2Я
Growth-Inhibiting and
Cell-Cycle Controls
Mutations That Promote Unregulated Passage from
G, to
Loss-of-Function Mutations Affecting Chromatin-
Remodeling Proteins Contribute to Tumors
Loss of p53 Abolishes the DNA-Damage Checkpoint
Apoptotic Genes Can Function as Proto-oncogenes
or Tumor-Suppressor Genes
Failure of Cell-Cycle Checkpoints Often Leads to
Aneuploidy in Tumor Cells
Carcinogens and Caretaker Genes
in Cancer
Carcinogens Induce Cancer by Damaging
Some Carcinogens Have Been Linked to
Specific Cancers
Loss of DNA-Repair Systems Can Lead to Cancer
Telomerase Expression Contributes to
Immortalization of Cancer Cells
GLOSSARY G-1
INDEX
CONTENTS
XXXVII |
| any_adam_object | 1 |
| any_adam_object_boolean | 1 |
| author_GND | (DE-588)125008473 |
| building | Verbundindex |
| bvnumber | BV022496802 |
| classification_rvk | WD 4150 WE 2400 |
| classification_tum | CHE 800f BIO 220f BIO 200f BIO 180f |
| ctrlnum | (OCoLC)318399428 (DE-599)BVBBV022496802 |
| dewey-full | 574.87 |
| dewey-hundreds | 500 - Natural sciences and mathematics |
| dewey-ones | 574 - [Unassigned] |
| dewey-raw | 574.87 |
| dewey-search | 574.87 |
| dewey-sort | 3574.87 |
| dewey-tens | 570 - Biology |
| discipline | Biologie Chemie |
| discipline_str_mv | Biologie Chemie |
| edition | 6. ed. |
| format | Book |
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| genre | 1\p (DE-588)4006432-3 Bibliografie gnd-content 2\p (DE-588)4123623-3 Lehrbuch gnd-content |
| genre_facet | Bibliografie Lehrbuch |
| id | DE-604.BV022496802 |
| illustrated | Illustrated |
| index_date | 2024-07-02T17:53:42Z |
| indexdate | 2024-07-09T20:58:53Z |
| institution | BVB |
| isbn | 9781429203142 9780716776017 0716776014 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-015703921 |
| oclc_num | 318399428 |
| open_access_boolean | |
| owner | DE-20 DE-355 DE-BY-UBR DE-703 DE-19 DE-BY-UBM DE-29T DE-M49 DE-BY-TUM DE-634 DE-11 DE-188 DE-91G DE-BY-TUM |
| owner_facet | DE-20 DE-355 DE-BY-UBR DE-703 DE-19 DE-BY-UBM DE-29T DE-M49 DE-BY-TUM DE-634 DE-11 DE-188 DE-91G DE-BY-TUM |
| physical | Getr. Zählung Ill., graph. Darst. |
| publishDate | 2008 |
| publishDateSearch | 2008 |
| publishDateSort | 2008 |
| publisher | Freeman |
| record_format | marc |
| spelling | Molekulare Zellbiologie Molecular cell biology Harvey Lodish ... 6. ed. New York Freeman 2008 Getr. Zählung Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Erg. bildet: Solutions manual to accompany Molecular cell biology. - Hier auch später erschienene, unveränderte Nachdrucke Cells cabt Molecular Biology cabt Cellular Biology cabt Biología molecular Citología Molekularbiologie (DE-588)4039983-7 gnd rswk-swf Cytologie (DE-588)4070177-3 gnd rswk-swf Zelle (DE-588)4067537-3 gnd rswk-swf CD-ROM (DE-588)4139307-7 gnd rswk-swf 1\p (DE-588)4006432-3 Bibliografie gnd-content 2\p (DE-588)4123623-3 Lehrbuch gnd-content Cytologie (DE-588)4070177-3 s Molekularbiologie (DE-588)4039983-7 s CD-ROM (DE-588)4139307-7 s 3\p DE-604 Zelle (DE-588)4067537-3 s 4\p DE-604 Lodish, Harvey 1941- Sonstige (DE-588)125008473 oth http://www.whfreeman.com/lodish6e Buchbegleitseiten Digitalisierung UB Regensburg application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=015703921&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk 2\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk 3\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk 4\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk |
| spellingShingle | Molecular cell biology Cells cabt Molecular Biology cabt Cellular Biology cabt Biología molecular Citología Molekularbiologie (DE-588)4039983-7 gnd Cytologie (DE-588)4070177-3 gnd Zelle (DE-588)4067537-3 gnd CD-ROM (DE-588)4139307-7 gnd |
| subject_GND | (DE-588)4039983-7 (DE-588)4070177-3 (DE-588)4067537-3 (DE-588)4139307-7 (DE-588)4006432-3 (DE-588)4123623-3 |
| title | Molecular cell biology |
| title_alt | Molekulare Zellbiologie |
| title_auth | Molecular cell biology |
| title_exact_search | Molecular cell biology |
| title_exact_search_txtP | Molecular cell biology |
| title_full | Molecular cell biology Harvey Lodish ... |
| title_fullStr | Molecular cell biology Harvey Lodish ... |
| title_full_unstemmed | Molecular cell biology Harvey Lodish ... |
| title_short | Molecular cell biology |
| title_sort | molecular cell biology |
| topic | Cells cabt Molecular Biology cabt Cellular Biology cabt Biología molecular Citología Molekularbiologie (DE-588)4039983-7 gnd Cytologie (DE-588)4070177-3 gnd Zelle (DE-588)4067537-3 gnd CD-ROM (DE-588)4139307-7 gnd |
| topic_facet | Cells Molecular Biology Cellular Biology Biología molecular Citología Molekularbiologie Cytologie Zelle CD-ROM Bibliografie Lehrbuch |
| url | http://www.whfreeman.com/lodish6e http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=015703921&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | UT molekularezellbiologie AT lodishharvey molecularcellbiology |