Molecular biology of the cell:
Gespeichert in:
| Hauptverfasser: | , , , , , , |
|---|---|
| Format: | Buch |
| Sprache: | English |
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New York, NY [u.a.]
Garland Science, Taylor & Francis Group
2015
|
| Ausgabe: | Sixth edition, international student edition |
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | xxxiv, 1342, G34, I53, T1 Seiten Illustrationen, Diagramme |
| ISBN: | 9780815344322 9780815344643 |
Internformat
MARC
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| 245 | 1 | 0 | |a Molecular biology of the cell |c Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts und Peter Walter |
| 246 | 1 | 3 | |a The cell |
| 250 | |a Sixth edition, international student edition | ||
| 264 | 1 | |a New York, NY [u.a.] |b Garland Science, Taylor & Francis Group |c 2015 | |
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Datensatz im Suchindex
| _version_ | 1811252360034385920 |
|---|---|
| adam_text |
Detailed Contents
Chapter
1
Cells and Genomes
1
THE UNIVERSAL FEATURES OF CELLS ON EARTH
2
All Cells Store Their Hereditary Information in the Same Linear
Chemical Code:
DNA 2
All Cells Replicate Their Hereditary Information by Templated
Polymerization
3
All Cells Transcribe Portions of Their Hereditary Information Into
the Same Intermediary Form:
RNA
4
All Cells Use Proteins as Catalysts
5
All Cells Translate
RNA
into Protein in the Same Way
6
Each Protein Is Encoded by a Specific Gene
7
Life Requires Free Energy
8
All Cells Function as Biochemical Factories Dealing with the Same
Basic Molecular Building Blocks
8
All Cells Are Enclosed In a Plasma Membrane Across Which
Nutrients and Waste Materials Must Pass
8
A Living Cell Can Exist with Fewer Than
500
Genes
9
Summary
10
THE DIVERSITY OF GENOMES AND THE TREE OF LIFE
10
Cells Can Be Powered by a Variety of Free-Energy Sources
10
Some Cells Fix Nitrogen and Carbon Dioxide for Others
12
The Greatest Biochemical Diversity Exists Among Prokaryotlc Cells
12
The Tree of Life Has Three Primary Branches: Bacteria, Archaea,
and Eukaryotes
14
Some Genes Evolve Rapidly; Others Are Highly Conserved
15
Most Bacteria and Archaea Have
1000-6000
Genes
16
New Genes Are Generated from Preexisting Genes
16
Gene Duplications Give Rise to Families of Related Genes Within
a Single Cell
17
Genes Can Be Transferred Between Organisms, Both in the
Laboratory and in Nature
18
Sex Results in Horizontal Exchanges of Genetic Information
Within a Species
19
The Function of a Gene Can Often Be Deduced from Its Sequence
20
More Than
200
Gene Families Are Common to All Three Primary
Branches of the Tree of Life
20
Mutations Reveal the Functions of Genes
21
Molecular Biology Began with a Spotlight on
£
coli
22
Summary
22
GENETIC INFORMATION IN EUKARYOTES
23
Eukaryotic Cells May Have Originated as Predators
24
Modern Eukaryotic Cells Evolved from a Symbiosis
25
Eukaryotes Have Hybrid Genomes
27
Eukaryotic Genomes Are Big
28
Eukaryotic Genomes Are Rich in Regulatory
DNA 29
The Genome Defines the Program of
Multicelular
Development
29
Many Eukaryotes Live as Solitary Cells
30
A Yeast Serves as a Minimal Model Eukaryote
30
The Expression Levels of All the Genes of An Organism
Can Be Monitored Simultaneously
32
Arabidopsis Has Been Chosen Out of
300,000
Species
As a Model Rant
32
The World of Animal Cells Is Represented By a Worm, a Fly,
a Fish, a Mouse, and a Human
33
Studies in
Drosophila
Provide a Key to Vertebrate Development
33
The Vertebrate Genome Is a Product of Repeated Duplications
34
The Frog and the Zebrafish Provide Accessible Models for
Vertebrate Development
35
The Mouse Is the Predominant Mammalian Model Organism
35
Humans Report on Their Own Peculiarities
36
We Are All Different in Detail
38
To Understand Cells and Organisms Will Require Mathematics,
Computers, and Quantitative Information
38
Summary
39
Problems
39
References
41
Chapter
2
Cell Chemistry and Bioenergetics
43
THE CHEMICAL COMPONENTS OF A CELL
43
Water Is Held Together by Hydrogen Bonds
44
Four Types of Noncovalent Attractions Help Bring Molecules
Together in Cells
44
Some Polar Molecules Form Acids and Bases in Water
45
A Cell Is Formed from Carbon Compounds
47
Cells Contain Four Major Families of Small Organic Molecules
47
The Chemistry of Cells Is Dominated by Macromolecules with
Remarkable Properties
47
Noncovalent Bonds Specify Both the Precise Shape of a
Macromolecule
and Its Binding to Other Molecules
49
Summary
50
CATALYSIS AND THE USE OF ENERGY BY CELLS
51
Cell Metabolism Is Organized by Enzymes
51
Biological Order Is Made Possible by the Release of Heat Energy
from Cells
52
Cells Obtain Energy by the Oxidation of Organic Molecules
54
Oxidation and Reduction Involve Electron Transfers
55
Enzymes Lower the Activation-Energy Barriers That Block
Chemical Reactions
57
Enzymes Can Drive Substrate Molecules Along Specific Reaction
Pathways
58
How Enzymes Find Their Substrates: The Enormous Rapidity of
Molecular Motions
59
The Free-Energy Change for a Reaction,
AG,
Determines Whether
It Can Occur Spontaneously
60
The Concentration of Reactants Influences the Free-Energy
Change and a Reaction's Direction
61
The Standard Free-Energy Change,
AG0,
Makes It Possible
to Compare the Energetics of Different Reactions
61
The Equilibrium Constant and
N3"
Are Readily Derived from
Each Other
62
The Free-Energy Changes of Coupled Reactions Are Additive
63
Activated Carrier Molecules Are Essential for Biosynthesis
63
The Formation of an Activated Carrier Is Coupled to an
Energetically Favorable Reaction
64
ATP Is the Most Widely Used Activated Carrier Molecule
65
Energy Stored in ATP Is Often Harnessed to Join Two Molecules
Together
65
NADH and NADPH Are Important Electron Carriers
67
There Are Many Other Activated Carrier Molecules in Cells
68
The Synthesis of Biological Polymers Is Driven by ATP Hydrolysis
70
Summary
73
HOW CELLS OBTAIN ENERGY FROM FOOD
73
Glycolysis Is a Central ATP-Producing Pathway
74
Fermentations Produce ATP in the Absence of Oxygen
75
xxii
DETAILED CONTENTS
Glycoiysis Illustrates How Enzymes Couple Oxidation to Energy
'
Storage
76
Organisms Store Food Molecules in Special Reservoirs
78
Most Animal Cells Derive Their Energy from Fatty Acids Between
Meals
"' 81
Sugars and Fats Are Both Degraded to
Acetyl
CoA in Mitochondria
81
The Citric Acid Cycle Generates NADH by Oxidizing
Acetyl
Groups to CO2
82
Electron Transport Drives the Synthesis of the Majority of the ATP
in Most Cells
84
Amino
Acids and Nucleotides Are Part of the Nitrogen Cycle
85
Metabolism Is Highly Organized and Regulated
87
Summary
88
Problems
88
References
108
Chapter
3
Proteins
109
THE SHAPE AND STRUCTURE OF PROTEINS
109
The Shape of a Protein Is Specified by Its
Amino
Acid Sequence
109
Proteins Fold into a Conformation of Lowest Energy
114
The
α
Helix and the
β
Sheet Are Common Folding Patterns
115
Protein Domains Are Modular Units from Which Larger Proteins
Are Built
117
Few of the Many Possible Polypeptide Chains Will Be Useful
to Cells
118
Proteins Can Be Classified into Many Families
119
Some Protein Domains Are Found in Many Different Proteins
121
Certain Pairs of Domains Are Found Together in Many Proteins
122
The Human Genome Encodes a Complex Set of Proteins,
Revealing That Much Remains Unknown
122
Larger Protein Molecules Often Contain More Than One
Polypeptide Chain
123
Some Globular Proteins Form Long Helical Filaments
123
Many Protein Molecules Have Elongated, Fibrous Shapes
124
Proteins Contain a Surprisingly Large Amount of Intrinsically
Disordered Polypeptide Chain
125
Covalent Cross-Linkages Stabilize Extracellular Proteins
127
Protein Molecules Often Serve as Subunits for the Assembly
of Large Structures
127
Many Structures in Cells Are Capable of Self-Assembly
128
Assembly Factors Often Aid the Formation of Complex Biological
Structures
130
Amyloid Fibrils Can Form from Many Proteins
130
Amyloid Structures Can Perform Useful Functions in Cells
132
Many Proteins Contain Low-complexity Domains that Can Form
"Reversible Amyloids"
132
Summary
134
PROTEIN FUNCTION
134
Ali
Proteins Bind to Other Molecules
134
The Surface Conformation of a Protein Determines Its Chemistry
135
Sequence Comparisons Between Protein Family Members
Highlight Crucial Ligand-Binding Sites
136
Proteins Bind to Other Proteins Through Several Types of
Interfaces
137
Antibody Binding Sites Are Especially Versatile
138
The Equilibrium Constant Measures Binding Strength
138
Enzymes Are Powerful and Highly Specific Catalysts
140
Substrate Binding Is the First Step in Enzyme Catalysis
141
Enzymes Speed Reactions by Selectively Stabilizing Transition
States
141
Enzymes Can Use Simultaneous Acid and Base Catalysis
144
Lysozyme Illustrates How an Enzyme Works
144
Tightly Bound Small Molecules Add Extra Functions to Proteins
146
Muitienzyme Complexes Help to increase the Rate of Cell
Metabolism
1
aq
The Cell Regulates the Catalytic Activities of Its Enzymes
149
Allosteric Enzymes Have Two or More Binding Sites That Interact
151
Two Ligands Whose Binding Sites Are Coupled Must Reciprocally
Affect Each Other's Binding
151
Symmetric Protein Assemblies Produce Cooperative Allosteric
Transitions
152
Many Changes in Proteins Are Driven by Protein Phosphorylation
153
A Eukaryotic Cell Contains a Large Collection of Protein Kinases
and Protein Phosphatases
154
The Regulation
oí
the Src Protein Kinase Reveals How a Protein
Can Function as a Microprocessor
155
Proteins That Bind and Hydrolyze GTP Are Ubiquitous Cell
Regulators
156
Regulatory Proteins GAP and GEF Control the Activity of GTP-
Binding Proteins by Determining Whether GTP or GDP
Is Bound
157
Proteins Can Be Regulated by the Covalent Addition of Other
Proteins
157
An Elaborate Ubiquitin-Conjugating System Is Used to Mark
Proteins
158
Protein Complexes with Interchangeable Parts Make Efficient
Use of Genetic Information
159
A GTP-Binding Protein Shows How Large Protein Movements
Can Be Generated
160
Motor Proteins Produce Large Movements in Cells
161
Membrane-Bound Transporters Harness Energy to Pump
Molecules Through Membranes
163
Proteins Often Form Large Complexes That Function as Protein
Machines
164
Scaffolds Concentrate Sets of Interacting Proteins
164
Many Proteins Are Controlled by Covalent Modifications That
Direct Them to Specific Sites Inside the Cell
165
A Complex Network of Protein Interactions Underlies Cell Function
166
Summary
169
Problems
170
References
172
Chapter
4 DNA,
Chromosomes, and Genomes
175
THE STRUCTURE AND FUNCTION OF
DNA
A
DNA
Molecule Consists of Two Complementary Chains of
Nucleotides
The Structure of
DNA
Provides a Mechanism for Heredity
In
Eukaryotes, DNA
Is Enclosed in a Cell Nucleus
Summary
CHROMOSOMAL
DNA
AND ITS PACKAGING IN THE
CHROMATIN FIBER
Eukaryotic
DNA
Is Packaged into a Set of Chromosomes
Chromosomes Contain Long Strings of Genes
The Nudeotide Sequence of the Human Genome Shows How
Our Genes Are Arranged
Each
DNA
Molecule That Forms a Linear Chromosome Must
Contain a Centromere, Two Telomeres, and Replication
Origins
DNA
Molecules Are Highly Condensed in Chromosomes
Nucleosomes Are a Basic Unit of Eukaryotic Chromosome
Structure
The Structure of the Nucleosome Core Particle Reveals How
DNA
Is Packaged
Nucleosomes Have a Dynamic Structure, and Are Frequently
Subjected to Changes Catalyzed by ATP-Dependent
Chromatin Remodeling Complexes
Nucleosomes Are Usually Packed Together into a Compact
Chromatin Fiber
Summary
CHROMATIN STRUCTURE AND FUNCTION
Heterochromatin is Highly Organized and Restricts Gene
Expression
The Heterochromatic State Is Self-Propagating
The Core Histones Are Covalently Modified at Many Different Sites
Chromatin Acquires Additional Variety Through the Site-Specific
Insertion of a Small Set of Histone Variants
Covalent Modifications and Histone Variants Act in Concert to
Control Chromosome Functions
A Complex of Reader and Writer Proteins Can Spread Specific
Chromatin Modifications Along a Chromosome
Barrier
DNA
Sequences Block the Spread of Reader-Writer
Complexes and thereby Separate Neighboring Chromatin
Domains
The Chromatin in Centromeres Reveals How Histone Variants
Can Create Special Structures
Some Chromatin Structures Can Be Directly Inherited
175
175
177
178
179
179
180
182
183
185
187
187
188
190
191
193
194
194
194
196
198
198
199
202
203
204
DETAILED CONTENTS
XXIII
Experiments with Frog Embryos Suggest that both Activating
and Repressive Chromatin Structures Can Be Inherited
Epigenetically
205
Chromatin Structures Are Important for Eukaryotic Chromosome
Function
206
Summary
207
THE GLOBAL STRUCTURE OF CHROMOSOMES
207
Chromosomes Are Folded into Large Loops of Chromatin
207
Polytene Chromosomes Are Uniquely Useful for Visualizing
Chromatin Structures
208
There Are Multiple Forms of Chromatin
210
Chromatin Loops
Decondense
When the Genes Within Them
Are Expressed
211
Chromatin Can Move to Specific Sites Within the Nucleus to
Alter Gene Expression
212
Networks of Macromolecules Form a Set of Distinct Biochemical
Environments inside the Nucleus
213
Mitotic Chromosomes Are Especially Highly Condensed
214
Summary
216
HOW GENOMES EVOLVE
216
Genome Comparisons Reveal Functional
DNA
Sequences by
their Conservation Throughout Evolution
217
Genome Alterations Are Caused by Failures of the Normal
Mechanisms for Copying and Maintaining
DNA,
as well as
by Transposable
DNA
Elements
217
The Genome Sequences of Two Species Differ in Proportion to
the Length of Time Since They Have Separately Evolved
218
Phylogenetic Trees Constructed from a Comparison of
DNA
Sequences Trace the Relationships of All Organisms
219
A Comparison of Human and Mouse Chromosomes Shows
How the Structures of Genomes Diverge
221
The Size of a Vertebrate Genome Reflects the Relative Rates
of
DNA
Addition and
DNA
Loss in a Lineage
222
We Can Infer the Sequence of Some Ancient Genomes
223
Multispecies Sequence Comparisons Identify Conserved
DNA
Sequences of Unknown Function
224
Changes in Previously Conserved Sequences Can Help
Decipher Critical Steps in Evolution
226
Mutations in the
DNA
Sequences That Control Gene Expression
Have Driven Many of the Evolutionary Changes in Vertebrates
227
Gene Duplication Also Provides an Important Source of Genetic
Novelty During Evolution
227
Duplicated Genes Diverge
228
The Evolution of the Globin Gene Family Shows How
DNA
Duplications Contribute to the Evolution of Organisms
229
Genes Encoding New Proteins Can Be Created by the
Recombination of Exons
230
Neutral Mutations Often Spread to Become Fixed in a Population,
with a Probability That Depends on Population Size
230
A Great Deal Can Be Learned from Analyses of the Variation
Among Humans
232
Summary
234
Problems
234
References
236
Chapter
5 DNA
Repiication. Repair, and
Recombination
237
THE MAINTENANCE OF
DNA
SEQUENCES
237
Mutation Rates Are Extremely Lew
237
Low Mutation Rates Are Necessary for Life as We Know It
238
Summary
239
DNA
REPLICATION MECHANISMS
239
Base-Pairing Underlies
DNA FtepFcaťcn
ana
DNA
Repair
239
The DNA
Replication Fork Is Asymmetrical
240
The High Fidelity of
DNA
Replication Requires Several
Proofreading Mechanisms
242
Only
DNA
Repiication in the 5'-tc-3' Direction Allows Efficient
Error Correction
244
A Special Nucleotide-Polymenzing Enzyme Synthesizes Short
RNA
Primer Molecules on
tne
Lagging Strand
245
Special Proteins Help to Open Up the
DNA
Double Helix in Front
of the Replication Fork
246
A Sliding Ring Holds a Moving
DNA Poiymerase
Onto the
DNA 246
The Proteins at a Replication Fork Cooperate to Form a
Replication Machine
249
A Strand-Directed Mismatch Repair System Removes Replication
Errors That Escape from the Replication Machine
250
DNA Topoisomerases
Prevent
DNA
Tangling During Replication
251
DNA
Replication is Fundamentally Similar in Eukaryotes and
Bacteria
253
Summary
254
THE INITIATION AND COMPLETION OF
DNA
REPLICATION
IN CHROMOSOMES
254
DNA
Synthesis Begins at Replication Origins
254
Bacterial Chromosomes Typically Have a Single Origin of
DNA
Replication
255
Eukaryotic Chromosomes Contain Multiple Origins of Replication
256
In Eukaryotes,
DNA
Replication Takes Place During Only One
Part of the Cell Cycle
258
Different Regions on the Same Chromosome Replicate at Distinct
Times in
S
Phase
258
A Large Multisubunit Complex Binds to Eukaryotic Origins of
Replication
259
Features of the Human Genome That Specify Origins of
Replication Remain to Be Discovered
260
New Nucleosomes Are Assembled Behind the Replication Fork
261
Telomerase Replicates the Ends of Chromosomes
262
Telomeres Are Packaged Into Specialized Structures That
Protect the Ends of Chromosomes
263
Telomere Length Is Regulated by Cells and Organisms
264
Summary
265
DNA
REPAIR
266
Without
DNA
Repair, Spontaneous
DNA
Damage Would Rapidly
Change
DNA
Sequences
267
The
DNA
Double Helix Is Readily Repaired
268
DNA
Damage Can Be Removed by More Than One Pathway
269
Coupling Nucleotide Excision Repair to Transcription Ensures
That the Cell's Most Important
DNA
Is Efficiently Repaired
271
The Chemistry of the
DNA
Bases Facilitates Damage Detection
271
Special
Translesion DNA Polymerases
Are Used in Emergencies
273
Double-Strand Breaks Are Efficiently Repaired
273
DNA
Damage Delays Progression of the Cell Cycle
276
Summary
276
HOMOLOGOUS RECOMBINATION
276
Homologous Recombination Has Common Features in Ail Cells
277
DNA
Base-Pairing Guides Homologous Recombination
277
Homologous Recombination Can Flawlessly Repair Double-
Strand Breaks in
DNA 278
Strand Exchange Is Carried Out by the
RecA/Radöl
Protein
279
Homologous Recombination Can Rescue Broken
DNA
Replication Forks
280
Cells Carefully Regulate the Use of Homologous Recombination
in
DNA
Repair
280
Homologous Recombination Is
Cruciai
for Meiosis
282
Meiotic Recombination Begins with a Programmed Double-Strand
Break
282
Holliday Junctions Are Formed During Meiosis
284
Homologous Recombination Produces Both Crossovers and
Non-Crossovers During Meiosis
284
Homologous Recombination Often Results in Gene Conversion
286
Summary
286
TRANSPOSITION AND CONSERVATIVE SITE-SPECIFIC
RECOMBINATION
287
Through Transposition, Mobile Genetic
Bements
Can Insert
Into Any
DNA
Sequence
288
DNA-Only
Transposons
Can Move by a Cut-and-Paste
Mechanism
238
Some Viruses Use a Transposition Mechanism to Move
Themselves Into Host-Cell Chromosomes
290
Retrovirai-like Retrotransposons Resemble Retroviruses, but
Lack a Protein Coat
291
A Large Fraction of the Human Genome Is Composed of
Nonretrovirat Retrotransposons
291
Different Transposable Elements Predominate in Different
Organisms
292
Genome Sequences Reveal the Approximate Times at Which
Transposabie Elements Have Moved
292
xxiv
DETAILED CONTENTS
292
294
294
295
296
298
Conservative Site-Specific Recombination Can Reversibly
Rearrange
DNA
Conservative Site-Specific Recombination Can Be Used to
Turn Genes On or Off
Bacterial Conservative Site-Specific Recombinases Have Become
Powerful Tools for Cell and Developmental Biologists
Summary
Problems
References
Chapter
6
How Cells Read the Genome:
From
DNA
to Protein
299
FROM
DNA
TO
RNA
301
RNA
Molecules Are Single-Stranded
302
Transcription Produces
RNA
Complementary to One Strand
of
DNA 302
RNA Polymerases
Carry Out Transcription
303
Cells Produce Different Categories of
RNA
Molecules
305
Signals Encoded in
DNA
Tell
RNA Polymerase
Where to Start
and Stop
' 306
Transcription Start and Stop Signals Are Heterogeneous in
Nucleotide Sequence
307
Transcription Initiation in Eukaryotes Requires Many Proteins
309
RNA
Polymerase II Requires a Set of General Transcription
Factors
310
Polymerase II Also Requires Activator, Mediator, and Chromatin-
Modifying Proteins
312
Transcription Elongation in Eukaryotes Requires Accessory
Proteins
313
Transcription Creates Superhelical Tension
314
Transcription Elongation in Eukaryotes Is Tightly Coupled to
RNA
Processing
315
RNA
Capping Is the First Modification of Eukaryotic Pre-mRNAs
316
RNA
Splicing Removes
Intron
Sequences from Newly
Transcribed Pre-mRNAs
317
Nucleotide Sequences Signal Where Splicing Occurs
319
RNA
Splicing Is Performed by the Spliceosome
319
The Spliceosome Uses ATP Hydrolysis to Produce a Complex
Series of RNA-RNA Rearrangements
321
Other Properties of Pre-mRNA and Its Synthesis Help to Explain
the Choice of Proper Splice Sites
321
Chromatin Structure Affects
RNA
Splicing
323
RNA
Splicing Shows Remarkable Plasticity
323
Spliceosome-Catalyzed
RNA
Splicing Probably Evolved from
Self-spücing
Mechanisms
324
RNA-Processing Enzymes Generate the
3'
End of Eukaryotic
mRNAs
324
Mature Eukaryotic mRNAs Are Selectively Exported from the
Nucleus
325
Noncoding RNAs Are Also Synthesized and Processed in the
Nucleus
327
The Nucleolus Is a Ribosome-Producing Factory
329
The Nucleus Contains a Variety of Subnuclear Aggregates
331
Summary
333
FROM
RNA
TO PROTEIN
333
An mRNA Sequence Is Decoded in Sets of Three Nucleotides
334
tRNA Molecules Match
Amino
Acids to
Codons
in mRNA
334
tRNAs Are Covalently Modified Before They Exit from the Nucleus
336
Specific Enzymes Couple Each
Amino
Acid to Its Appropriate
tRNA Molecule
336
Editing by
îRNA Synthetases
Ensures Accuracy
338
Amino
Acids Are Added to the
C-terminal
End of a Growing
Poiypeptide Chain
" 339
The
RNA
Message Is Decoded in Ribosomes
340
Elongation Factors Drive Translation Forward and Improve Its
Accuracy
343
Many Biological Processes Overcome the Inherent Limitations of
Complementary Base-Pairing
345
Accuracy in Translation Requires an Expenditure of Free Energy
345
The Ribosome ¡s a Ribozyme
346
Nucieotide Sequences in mRNA Signal Where to Start Protein
Synthesis
347
Stop
Codons
Mark
tne
End of Translation
348
Proteins Are Made on Polyribosomes
There Are Minor Variations in the Standard Genetic Code
Inhibitors of Prokaryotic Protein Synthesis Are Useful as
Antibiotics
Quality Control Mechanisms Act to Prevent Translation of
Damaged mRNAs
Some Proteins Begin to Fold While Still Being Synthesized
Molecular Chaperones Help Guide the Folding of Most Proteins
Cells Utilize Several Types of Chaperones
Exposed
Hydrophobie
Regions Provide Critical Signals for
Protein Quality Control
The Proteasome Is a Compartmentalized Protease with
Sequestered Active Sites
Many Proteins Are Controlled by Regulated Destruction
There Are Many Steps From
DNA
to Protein
Summary
THE
RNA
WORLD AND THE ORIGINS OF LIFE
Single-Stranded
RNA
Molecules Can Fold into Highly Elaborate
Structures
RNA
Can Both Store Information and Catalyze Chemical
Reactions
How Did Protein Synthesis Evolve?
All Present-Day Cells Use
DNA
as Their Hereditary Material
Summary
Problems
References
Chapter
7
Control of Gene Expression
AN OVERVIEW OF GENE CONTROL
The Different Cell Types of
a Multicelular
Organism Contain
the Same
DNA
Different Cell Types Synthesize Different Sets of RNAs and
Proteins
External Signals Can Cause a Cell to Change the Expression
of Its Genes
Gene Expression Can Be Regulated at Many of the Steps
in the Pathway from
DNA
to
RNA
to Protein
Summary
CONTROL OF TRANSCRIPTION BY SEQUENCE-SPECIFIC
DNA-BINDING PROTEINS
The Sequence of Nucleotides in the
DNA
Double Helix Can Be
Read by Proteins
Transcription Regulators Contain Structural Motifs That Can
Read
DNA
Sequences
Dimerization of Transcription Regulators Increases Their Affinity
and Specificity for
DNA
Transcription Regulators Bind Cooperatively to
DNA
Nucleosome Structure Promotes Cooperative Binding of
Transcription Regulators
Summary
TRANSCRIPTION REGULATORS SWITCH GENES ON
AND OFF
The Tryptophan
Repressor
Switches Genes Off
Repressors Turn Genes Off and Activators Turn Them On
An Activator and
a Repressor
Control the Lac Operon
DNA
Looping Can Occur During Bacterial Gene Regulation
Complex Switches Control Gene Transcription in Eukaryotes
A Eukaryotic Gene Control Region Consists of a Promoter
Plus Many c/s-Regulatory Sequences
Eukaryotic Transcription Regulators Work in Groups
Activator Proteins Promote the Assembly of
RNA
Polymerase
at the Start Point of Transcription
Eukaryotic Transcription Activators Direct the Modification of
Local Chromatirt Structure
Transcription Activators Can Promote Transcription by Releasing
RNA
Polymerase from Promoters
Transcription Activators Work Synergistically
Eukaryotic Transcription Repressors Can Inhibit Transcription
in Several Ways
Insulator
DNA
Sequences Prevent Eukaryotic Transcription
Regulators from Influencing Distant Genes
Summary
349
349
351
351
353
354
355
357
357
359
361
362
362
363
364
365
365
366
366
368
369
369
369
370
372
372
373
373
373
374
375
378
379
380
380
380
381
382
383
384
384
385
386
386
388
388
389
391
392
DETAILED CONTENTS
xxv
MOLECULAR GENETIC MECHANISMS THAT CREATE AND
MAINTAIN SPECIALIZED CELL TYPES
392
Complex Genetic Switches That Regulate
Drosophila
Development Are Built Up from Smaller Molecules
392
The
Drosophila
Eve Gene Is Regulated by Combinatorial Controls
394
Transcription Regulators Are Brought Into Play by Extracellular
Signals
395
Combinatorial Gene Control Creates Many Different Cell Types
396
Specialized Cell Types Can Be Experimentally Reprogrammed
to Become Pluripotent Stem Cells
398
Combinations of Master Transcription Regulators Specify Cell
Types by Controlling the Expression of Many Genes
398
Specialized Cells Must Rapidly Turn Sets of Genes On and Off
399
Differentiated Cells Maintain Their Identity
400
Transcription Circuits Allow the Cell to Carry Out Logic Operations
402
Summary
404
MECHANISMS THAT REINFORCE CELL MEMORY IN
PLANTS AND ANIMALS
404
Patterns of
DNA Methylation
Can Be Inherited When Vertebrate
Cells Divide
404
CG-Rich Islands Are Associated with Many Genes in Mammals
405
Genomic Imprinting Is Based on
DNA
Methylation
407
Chromosome-Wide Alterations in Chromatin Structure Can Be
Inherited
409
Epigenetic Mechanisms Ensure That Stable Patterns of Gene
Expression Can Be Transmitted to Daughter Cells
411
Summary
413
POST-TRANSCRIPTIONAL CONTROLS
413
Transcription Attenuation Causes the Premature Termination of
Some
RNA
Molecules
414
Riboswitches Probably Represent Ancient Forms of Gene Control
414
Alternative
RNA
Splicing Can Produce Different Forms of a Protein
from the Same Gene
415
The Definition of a Gene Has Been Modified Since the Discovery
of Alternative
RNA
Splicing
416
A Change in the Site of
RNA
Transcript Cleavage and Poly-A
Addition Can Change the
С
-terminus
of a Protein
417
RNA
Editing Can Change the Meaning of the
RNA
Message
418
RNA
Transport from the Nucleus Can Be Regulated
419
Some mRNAs Are Localized to Specific Regions of the Cytosol
421
The
5'
and
3'
Untranslated Regions of mRNAs Control Their
Translation
422
The Phosphorylation of an Initiation Factor Regulates Protein
Synthesis Globally
423
Initiation at
AUG
Codons
Upstream of the Translation Start Can
Regulate Eukaryotic Translation Initiation
424
Internal Ribosome Entry Sites Provide Opportunities for
Translational Control
425
Changes in mRNA Stability Can Regulate Gene Expression
426
Regulation of mRNA Stability Involves P-bodies and Stress
Granules
427
Summary
428
REGULATION OF GENE EXPRESSION BY NONCODING RNAs
429
Small Noncoding
RNA
Transcripts Regulate Many Animal and
Plant Genes Through
RNA
Interference
429
miRNAs Regulate mRNA Translation and Stability
429
RNA
Interference Is Also Used as a Cell Defense Mechanism
431
RNA
Interference Can Direct Heterochromatin Formation
432
piRNAs Protect the Germ Line from Transposable Elements
433
RNA
Interference Has Become a Powerful Experimental Tool
433
Bacteria Use Small Noncoding RNAs to Protect Themselves
from Viruses
433
Long Noncoding RNAs Have Diverse Functions in the Ceil
435
Summary
436
Problems
436
References
438
Chapter
8
Analyzing Cells. Molecules, and
Systems
439
ISOLATING CELLS AND GROWING THEM IN CULTURE
440
Cells Can Be Isolated from Tissues
440
Cells Can Be Grown in Culture
440
Eukaryotic Cell Lines Are a Widely Used Source of
Homogeneous Cells
442
Hybridoma Cell Lines Are Factories That Produce Monoclonal
Antibodies
444
Summary
445
PURIFYING PROTEINS
445
Cells Can Be Separated into Their Component Fractions
445
Cell Extracts Provide Accessible Systems to Study Cell Functions
447
Proteins Can Be Separated by Chromatography
448
Immunoprecipitation Is a Rapid Affinity Purification Method
449
Genetically Engineered Tags Provide an Easy Way to Purify
Proteins
450
Purified Cell-free Systems Are Required for the Precise
Dissection of Molecular Functions
451
Summary
451
ANALYZING PROTEINS
452
Proteins Can Be Separated by
SDS
Polyacrylamide-Gel
Electrophoresis
452
Two-Dimensional Gel Electrophoresis Provides Greater Protein
Separation
452
Specific Proteins Can Be Detected by Blotting with Antibodies
454
Hydrodynamic Measurements Reveal the Size and Shape of
a Protein Complex
455
Mass Spectrometry Provides a Highly Sensitive Method for
Identifying Unknown Proteins
455
Sets of Interacting Proteins Can Be Identified by Biochemical
Methods
" 457
Optical Methods Can Monitor Protein Interactions
458
Protein Function Can Be Selectively Disrupted With Small
Molecules
459
Protein Structure Can Be Determined Using
Х
-Ray Diffraction
460
NMR Can Be Used to Determine Protein Structure in Solution
461
Protein Sequence and Structure Provide Clues About Protein
Function
462
Summary
463
ANALYZING AND MANIPULATING
DNA 463
Restriction Nucleases Cut Large
DNA
Molecules into Specific
Fragments
464
Gel Electrophoresis Separates
DNA
Molecules of Different Sizes
465
Purified
DNA
Molecules Can Be Specifically Labeled with
Radioisotopes
or Chemical Markers in vitro
467
Genes Can Be Cloned Using Bacteria
467
An Entire Genome Can Be Represented in
a
DNA
Library
469
Genomic and cDNA Libraries Have Different Advantages and
Drawbacks
471
Hybridization Provides a Powerful, But Simple Way to Detect
Specific Nucleotide Sequences
472
Genes Can Be Cloned in vitro Using PCR
473
PCR Is Also Used for Diagnostic and Forensic Applications
474
Both
DNA
and
RNA
Can Be Rapidly Sequenced
477
To Be Useful, Genome Sequences Must Be Annotated
477
DNA
Cloning Allows Any Protein to be Produced in Large
Amounts
483
Summary
484
STUDYING GENE EXPRESSION AND FUNCTION
485
Classical Genetics Begins by Disrupting a Cell Process by
Random Mutagenesis
485
Genetic Screens Identify Mutants with Specific Abnormalities
488
Mutations Can Cause Loss or Gain of Protein Function
489
Complementation Tests Reveal Whether Two Mutations Are in the
Same Gene or Different Genes
490
Gene Products Can Be Ordered in Pathways by Epistasis
Analysis
490
Mutations Responsible for a Phenotype Can Be Identified
Through
DNA
Analysis
491
Rapid and Cheap
DNA
Sequencing Has Revolutionized
Human Genetic Studies
491
Linked Blocks of Polymorphisms Have Been Passed Down
from Our Ancestors
492
Polymorphisms Can Aid the Search for Mutations Associated
with Disease
493
Genomics Is Accelerating the Discovery of Rare Mutations That
Predispose Us to Serious Disease
493
Reverse Genetics Begins with a Known Gene and Determines
Which Cell Processes Require Its Function
494
Animals and Plants Can Be Genetically Altered
495
xxvi
DETAILED CONTENTS
The Bacterial CRISPR System Has Been Adapted to Edit
Genomes in a Wide Variety of Species
_ 497
Large Collections of Engineered Mutations Provide a Tool for
Examining the Function of Every Gene in an Organism
498
RNA
Interference Is a Simple and Rapid Way to Test Gene
Function
499
Reporter Genes Reveal When and Where a Gene Is Expressed
501
In situ Hybridization Can Reveal the Location of mRNAs and
Noncoding RNAs
502
Expression of Individual Genes Can Be Measured Using
Quantitative RT-PCR
502
Analysis of mRNAs by Microarray or RNA-seq Provides a
Snapshot of Gene Expression
503
Genome-wide Chromatin Immunoprecipitation Identifies Sites
on the Genome Occupied by Transcription Regulators
505
Ribosome Profiling Reveals Which mRNAs Are Being Translated
in the Cell
505
Recombinant
DNA
Methods Have Revolutionized Human Health
506
Transgenic Plants Are Important for Agriculture
507
Summary
508
MATHEMATICAL ANALYSIS OF CELL FUNCTIONS
509
Regulatory Networks Depend on Molecular interactions
509
Differential Equations Help Us Predict Transient Behavior
512
Both Promoter Activity and Protein Degradation Affect the Rate
of Change of Protein Concentration
513
The Time Required to Reach Steady State Depends on Protein
Lifetime
514
Quantitative Methods Are Similar for Transcription Repressors
and Activators
514
Negative Feedback Is a Powerful Strategy in Cell Regulation
515
Delayed Negative Feedback Can Induce Oscillations
516
DNA
Binding By
a Repressor
or an Activator Can Be Cooperative
516
Positivo
Feedback I« Important for Switchlike Responses
{■mrt
testability
518
Robustness Is an important Characteristic of Biological Networks
520
Two Transcription Regulators That Bind to the Same Gene
Promoter Can Exert Combinatorial Control
520
An Incoherent Feed-forward Interaction Generates Pulses
522
A Coherent Feed -forward Interaction Detects Persistent Inputs
522
The Same Network Can Behave Differently in Different Cells Due
to Stochastic Effects
523
Several Computational Approaches Can Be Used to Model the
Reactions in Cells
524
Statistical Methods Are Critical For the Analysis of Biological Data
524
Summary
525
Problems
525
References
528
Chapter
9
Visualizing Cells
529
LOOKING AT CELLS IN THE LIGHT MICROSCOPE
529
The Light Microscope Can Resolve Details
0.2
μηι
Apart
530
Photon Noise Creates Additional Limits to Resolution When
Light Levels Are Low
532
Living Cells Are Seen Clearly in a Phase-Contrast or a
Differential-Interference-Contrast Microscope
533
images Can Be Enhanced and Analyzed by Digital Techniques
534
Intact Tissues Are Usually Fixed and Sectioned Before Microscopy
535
Specie Molecules Can Be Located in Ceiis by Fluorescence
Microscopy
536
Antibodies Can Be Used to Detect Specific
Molécules
539
Imaging of Complex Three-Dimensional Objects is Possible with
the Optical Microscope 540
The Confacal Microscope Produces Optical Sections by
Excluding Out-of-Focus Light
540
individuai
Proteins Can Be Fluorescent^ Tagged in Living Cells
and Organisms
542
Protein
Dynamics Can Be Followed in Living Ceiis
543
Light-Emitting indicators Can Measure Rapidiy Changing
teacelluiar ton Concentrations
546
Single Molecules Can Be Visualized by
Tota! Internai
Reflection
Fluorescence Microscopy
547
Individuai
Molecules Can Be Touched. Imaged, and Moved Using
Atomic Force Microscopy
548
Superresolution
Fluorescence Techniques Can Overcome
Diffraction-Limited Resolution
Superresolution
Can Also be Achieved Using Single-Molecule
Localization Methods
Summary
LOOKING AT CELLS AND MOLECULES IN THE ELECTRON
MICROSCOPE
The Electron Microscope Resolves the Fine Structure of the Cell
Biological Specimens Require Special Preparation for Electron
Microscopy
Specific Macromolecules Can Be Localized by Immunogold
Electron Microscopy
Different Views of a Single Object Can Be Combined to Give
a Three-Dimensional Reconstruction
Images of Surfaces Can Be Obtained by Scanning Electron
Microscopy
Negative Staining and Cryoelectron Microscopy Both Allow
Macromolecules to Be Viewed at High Resolution
Multiple Images Can Be Combined to Increase Resolution
Summary
Problems
References
Chapter
10
Membrane Structure
THE
LIPID
BILAYER
Phosphoglycerides, Sphingolipids, and Sterols Are the Major
Lipids in Cell Membranes
Phospholipids Spontaneously Form Bilayers
The
Lipid Bilayer
Is a Two-dimensional Fluid
The Fluidity of
a Lipid Bilayer
Depends on Its Composition
Despite Their Fluidity,
Lipid
Bilayers Can Form Domains of
Different Compositions
Lipid
Droplets Are Surrounded by a Phospholipid Monolayer
The Asymmetry of the
Lipid Bilayer
Is Functionally Important
Glycolipids Are Found on the Surface of All Eukaryotic Plasma
Membranes
Summary
MEMBRANE PROTEINS
Membrane Proteins Can Be Associated with the
Lipid Bilayer
in Various Ways
Lipid
Anchors Control the Membrane Localization of Some
Signaling Proteins
In Most
Transmembrane
Proteins, the Poiypeptide Chain
Crosses the
Lipid Bilayer
in an a-Helical Conformation
Transmembrane
α
Helices Often Interact with One Another
Some
β
Barrels Form Large Channels
Many Membrane Proteins Are Glycosylated
Membrane Proteins Can Be Solubilized and Purified in Detergents
Bacteriorhodopsin Is a Light-driven Proton (H*) Pump That
Traverses the
Lipid Bilayer
as Seven
α
Helices
Membrane Proteins Often Function as Large Complexes
Many Membrane Proteins Diffuse in the Plane of the Membrane
Cells Can Confine Proteins and Lipids to Specific Domains
Within a Membrane
The Cortical Cytoskeleton Gives Membranes Mechanical
Strength and Restricts Membrane Protein Diffusion
Membrane-bending Proteins Deform Bilayers
Summary
Problems
References
549
551
554
554
554
555
556
557
558
559
561
562
563
564
565
566
566
568
569
571
572
573
573
575
576
576
576
577
579
580
580
582
583
586
588
588
590
591
593
594
595
596
Chapter
11
Membrane Transport of Small Molecules
and the Electrical Properties of Membranes
597
PRINCIPLES OF MEMBRANE TRANSPORT
597
Protein-Free
Lipid
Bilayers Are Impermeable to Ions
598
There Are Two Main Classes of Membrane Transport Proteins:
Transporters and Channels
598
Active Transport Is Mediated by Transporters Coupled to an
Energy Source
599
Summary
600
TRANSPORTERS AND ACTIVE MEMBRANE TRANSPORT
600
Active Transport Can Be Driven by Ion-Concentration Gradients
601
DETAILED CONTENTS
XXVII
Transporters in
the
Plasma Membrane
Regulate Cytosolic
pH 604
An Asymmetrie
Distribution of
Transporters in
Epithelial Cells
Underlies the Transcellular Transport of Solutes
605
There Are Three Classes of ATP-Driven Pumps
606
A P-type ATPase Pumps Ca2+ into the Sarcoplasmic Reticulum
in Muscle Cells
606
The Plasma Membrane Na+-K+ Pump Establishes Na+ and K+
Gradients Across the Plasma Membrane
607
ABC Transporters Constitute the Largest Family of Membrane
Transport Proteins
609
Summary
611
CHANNELS AND THE ELECTRICAL PROPERTIES OF
MEMBRANES
611
Aquaporins Are Permeable to Water But Impermeable to Ions
612
Ion Channels Are Ion-Selective and Fluctuate Between Open
and Closed States
613
The Membrane Potential in Animal Cells Depends Mainly on K+
Leak Channels and the K+ Gradient Across the Plasma
Membrane
615
The Resting Potential Decays Only Slowly When the Na+-K+
Pump Is Stopped
615
The Three-Dimensional Structure of a Bacterial K+ Channel
Shows How an Ion Channel Can Work
617
Mechanosensitive Channels Protect Bacterial Cells Against
Extreme Osmotic Pressures
619
The Function of a Neuron Depends on Its Elongated Structure
620
Voltage-Gated Cation Channels Generate Action Potentials in
Electrically Excitable Cells
621
The Use of Channelrhodopsins Has Revolutionized the Study
of Neural Circuits
623
Myelination Increases the Speed and Efficiency of Action Potential
Propagation In Nerve Cells
625
Patch-Clamp Recording Indicates That Individual Ion Channels
Open in an AII-or-Nothing Fashion
626
Voltage-Gated Cation Channels Are Evolutionarily and Structurally
Related
626
Different Neuron Types Display Characteristic Stable Firing
Properties
627
Transmitter-Gated ton Channels Convert Chemical Signals into
Electrical Ones at Chemical Synapses
627
Chemical Synapses Can Be Excitatory or Inhibitory
629
The Acetylcholine Receptors at the Neuromuscular Junction Are
Excitatory Transmitter-Gated Cation Channels
630
Neurons Contain Many Types of Transmitter-Gated Channels
631
Many Psychoactive Drugs Act at Synapses
631
Neuromuscular Transmission Involves the Sequential Activation
of Five Different Sets of Ion Channels
632
Single Neurons Are Complex Computation Devices
633
Neuronal
Computation Requires a Combination of at Least Three
Kinds of
К*
Channels
634
Long-Term Potentiation (LTP) in the Mammalian Hippocampus
Depends on Ca2' Entry Through NMDA-Receptor Channels
636
Summary
637
Problems
638
References
640
Chapter
12
intracellular Compartments and
Protein Sorting
641
THE COMPARTMENTALiZATION OF CELLS
641
AH Eukaryotic Cells Have the Same Basic Set of Membrane-
enclosed
Organelies
641
Evolutionary Origins May Help Exp^in the
Topologica
Relationships of Organsiies
6¿3
Proteins Can Move Between Compartments In Different Ways
645
Signal Sequences and Sorting Receptors Direct Proteins to the
Correct Ceil Address
" 647
Most Organelles Cannot Be
Ccnsîructed De
Novo:
They Require
Information in the Organelis 'tself
648
Summary
649
THE TRANSPORT OF MOLECULES BETWEEN THE
NUCLEUS AND THE CYTOSOL
649
Nuclear
Pore Complexes Perforate
tne
Nuclear Envelope
649
Nuclear Localization Signals Direct Nuclear Proteins to the Nucleus
650
Nuclear Import Receptors Bind to Both Nuclear Localization
Signals and NPC Proteins
652
Nuclear Export Works Like Nuclear Import, But in Reverse
652
The Ran GTPase Imposes Directionality on Transport Through
NPCs
653
Transport Through NPCs Can Be Regulated by Controlling
Access to the Transport Machinery
654
During Mitosis the Nuclear Envelope Disassembles
656
Summary
657
THE TRANSPORT OF PROTEINS INTO MITOCHONDRIA AND
CHLOROPLASTS
658
Translocation
into Mitochondria Depends on Signal Sequences
and Protein Translocators
659
Mitochondrial Precursor Proteins Are Imported as Unfolded
Polypeptide Chains
660
ATP Hydrolysis and a Membrane Potential Drive Protein Import
Into the Matrix Space
661
Bacteria and Mitochondria Use Similar Mechanisms to Insert
Porins into their Outer Membrane
662
Transport Into the Inner Mitochondrial Membrane and
Intermembrane
Space Occurs Via Several Routes
663
Two Signal Sequences Direct Proteins to the Thylakoid Membrane
in Chloroplasts
664
Summary
666
PEROXISOMES
666
Peroxisomes Use Molecular Oxygen and Hydrogen Peroxide
to Perform Oxidation Reactions
666
A Short Signal Sequence Directs the Import of Proteins into
Peroxisomes
667
Summary
669
THE ENDOPLASMIC RETICULUM
669
The
ER
Is Structurally and Functionally Diverse
670
Signal Sequences Were First Discovered in Proteins Imported
into the Rough
ER 672
A Signal-Recognition Particle
(SRP)
Directs the
ER
Signal
Sequence to a Specific Receptor in the Rough
ER
Membrane
673
The Polypeptide Chain Passes Through an Aqueous Channel
in the Translocator
675
Translocation
Across the
ER
Membrane Does Not Always
Require Ongoing Polypeptide Chain Elongation
677
In Single-Pass
Transmembrane
Proteins, a Single Internal
ER
Signal Sequence Remains in the
Lipid
Bilayer as a Membrane-
spanning
α
Helix
677
Combinations of Start-Transfer and Stop-Transfer Signals
Determine the Topology of Multipass
Transmembrane
Proteins
679
ER
Tail-anchored Proteins Are Integrated into the
ER
Membrane
by a Special Mechanism
682
Translocated Polypeptide Chains Fold and Assemble in the
Lumen of the Rough
ER 682
Most Proteins Synthesized in the Rough
ER Are
Giycosylated by
the Addition of a Common /V-Linked Oligosaccnaride
683
Oiigosaccharides Are Used as Tags to Mark the State of Protein
Folding
685
Improperly Folded Proteins Are Exported from the
ER
and
Degraded in the Cytosol
685
Misfoided Proteins in the
ER
Activate an Unfolded Protein
Response
686
Some Membrane Proteins Acquire a Covaiently Attached
Glycosyîphosphatidyiinositoï
ÍGPI)
Anchor
688
The
ER
Assembles Most
Lipid Bilayers
689
Summary
691
Problems
692
References
694
Chapter
13
Intraceiiuiar Membrane Traffic
695
THE MOLECULAR MECHANISMS OF MEMBRANE
TRANSPORT AND THE MAINTENANCE OF
COMPARTMENTAL DIVERSITY
697
There Are Various Types of Coated Vesicles
697
The Assembly of
a Claíhrín
Coat Drives Vesicle Formation
697
Adaptor Proteins Select Cargo into Ciathrin -Coated Vesicles
698
Phosphoinositides Mark Organelles and Membrane Domains
700
xxviii
DETAILED CONTENTS
Membrane-Bending Proteins Help Deform the Membrane During
Vesicle Formation
701
Cytoplasmic Proteins Regulate the Pinching-Off and Uncoating
of Coated Vesicles
701
Monomeric GTPases
Control Coat Assembly
703
Not All Transport Vesicles Are Spherical
704
Rab
Proteins Guide Transport Vesicles to Their Target Membrane
705
Rab
Cascades Can Change the Identity of an
Organelle 707
SNAREs Mediate Membrane Fusion
708
Interacting SNAREs Need to Be Pried Apart Before They Can
Function Again
709
Summary
710
TRANSPORT FROM THE
ER
THROUGH THE GOLGI
APPARATUS
710
Proteins Leave the
ER in
COPII-Coated Transport Vesicles
711
Only Proteins That Are Properly Folded and Assembled Can
Leave the
ER 712
Vesicular Tubular Clusters Mediate Transport from the
ER
to
the Golgi Apparatus
712
The Retrieval Pathway to the
ER
Uses Sorting Signals
713
Many Proteins Are Selectively Retained in the Compartments
in Which They Function
714
The Golgi Apparatus Consists of an Ordered Series of
Compartments
715
Oligosaccharide Chains Are Processed in the Golgi Apparatus
716
Proteoglycans Are Assembled in the Golgi Apparatus
718
What Is the Purpose of Glycosylation?
719
Transport Through the Golgi Apparatus May Occur by
Cisternal Maturation
720
Golgi Matrix Proteins Help Organize the Stack
721
Summary
722
TRANSPORT FROM THE TRANS GOLGI NETWORK TO
LYSOSOMES
722
Lysosomes Are the Principal Sites of Intracellular Digestion
722
Lysosomes Are Heterogeneous
723
Plant and Fungal
Vacuoles
Are Remarkably Versatile Lysosomes
724
Multiple Pathways Deliver Materials to Lysosomes
725
Autophagy Degrades Unwanted Proteins and
Organelies
726
A Mannose 6-Phosphate Receptor Sorts Lysosomal Hydrolases
in the Trans Golgi Network
727
Defects in the GlcNAc Phosphotransferase Cause a Lysosomal
Storage Disease in Humans
728
Some Lysosomes and Multivesicular Bodies Undergo
Exocytosis
729
Summary
729
TRANSPORT INTO THE CELL FROM THE PLASMA
MEMBRANE: ENDOCYTOSIS
730
Pinocytic Vesicles Form from Coated Pits in the Plasma
Membrane
731
Not All Pinocytic Vesicles Are Clathrin-Coated
731
Cells Use Receptor-Mediated Endocytosis to Import Selected
Extracellular Macromolecules
732
Specific Proteins Are Retrieved from Early Endosomes and
Returned to the Plasma Membrane
734
Plasma Membrane Signaling Receptors are Down-Regulated
by Degradation in Lysosomes
735
Early Endosomes Mature into Late Endosomes
735
ESCRT Protein Complexes Mediate the Formation of
Intralumenal Vesicles in Multivesicular Bodies
736
Recycling Endosomes Regulate Plasma Membrane Composition
737
Specialized Phagocytic Cells Can Ingest Large Particles
738
Summary
740
TRANSPORT FROM THE TRANS GOLGi NETWORK TO
THE CELL EXTERIOR: EXOCYTOSIS
741
Many Proteins and Lipids Are Carried Automatically from the
Trans Golgi Network (TGN) to the Cell Surface
741
Secretory Vesicles Bud from the Trans Golgi Network
742
Precursors of Secretory Proteins Are Proteoiytically Processed
During the Formation of Secretory Vesicles
743
Secretory Vesicles Wait Near the Plasma Membrane Until
Signaled to Release Their Contents
744
For Rapid Exocytosis, Synaptic Vesicles Are Primed at the
Presynaptic Plasma Membrane
744
Synaptic Vesicles Can Form Directly from Endocytic Vesicles
746
Secretory Vesicle Membrane Components Are Quickly Removed
from the Plasma Membrane
746
Some Regulated Exocytosis Events Serve to Enlarge the Plasma
Membrane
748
Polarized Cells Direct Proteins from the Trans Golgi Network
to the Appropriate Domain of the Plasma Membrane
748
Summary
750
Problems
750
References
752
Chapter
14
Energy Conversion: Mitochondria
and Chloroplasts
753
THE MITOCHONDRION
755
The Mitochondrion Has an Outer Membrane and an Inner
Membrane
757
The Inner Membrane Cristae Contain the Machinery for Electron
Transport and ATP Synthesis
758
The Citric Acid Cycle in the Matrix Produces NADH
758
Mitochondria Have Many Essential Roles in Cellular Metabolism
759
A Chemiosmotic Process Couples Oxidation Energy to ATP
Production
761
The Energy Derived from Oxidation Is Stored as an
Electrochemical Gradient
762
Summary
763
THE PROTON PUMPS OF THE ELECTRON-TRANSPORT
CHAIN
763
The
Redox
Potential Is a Measure of Electron Affinities
763
Electron Transfers Release Large Amounts of Energy
764
Transition Metal Ions and
Quiñones
Accept and Release
Electrons Readily
764
NADH Transfers Its Electrons to Oxygen Through Three
Large Enzyme Complexes Embedded in the Inner
Membrane
766
The NADH Dehydrogenase Complex Contains Separate
Modules for Electron Transport and Proton Pumping
768
Cytochrome
с
Reducíase
Takes Up and Releases Protons on
the Opposite Side of the
Crista
Membrane, Thereby
Pumping Protons
768
The Cytochrome
с
Oxidase
Complex Pumps Protons and
Reduces O2 Using a Catalytic Iron-Copper Center
770
The Respiratory Chain Forms a Supercomplex in the
Crista
Membrane
772
Protons Can Move Rapidly Through Proteins Along Predefined
Pathways
773
Summary
774
ATP PRODUCTION IN MITOCHONDRIA
774
The Large Negative Value of
AG
for ATP Hydrolysis Makes
ATP Useful to the Cell
774
The ATP Synthase Is a Nanomachine that Produces ATP by
Rotary Catalysis
776
Proton-driven Turbines Are of Ancient Origin
777
Mitochondria! Cristae Help to Make ATP Synthesis Efficient
778
Special Transport Proteins Exchange ATP and ADP Through
the Inner Membrane
779
Chemiosmotic Mechanisms First Arose in Bacteria
780
Summary
782
CHLOROPLASTS AND PHOTOSYNTHESIS
782
Chloroplasts Resemble Mitochondria But Have a Separate
Thylakoid Compartment
782
Chloroplasts Capture Energy from Sunlight and Use It to Fix
Carbon
783
Carbon Fixation Uses ATP and NADPH to Convert CO2 into
Sugars
784
Sugars Generated by Carbon Fixation Can Be Stored as
Starch or Consumed to Produce ATP
785
The Thylakoid Membranes of Chloroplasts Contain the Protein
Complexes Required for Photosynthesis and ATP Generation
786
Chlorophyll-Protein Complexes Can Transfer Either Excitation
Energy or Electrons
787
A
Photosystem
Consists of an Antenna Complex and a Reaction
Center
788
The Thylakoid Membrane Contains Two Different
Photosystems
Working in Series
789
DETAILED CONTENTS
XXIX
Photosystem
II Uses a
Manganese Cluster to Withdraw
Electrons From Water
790
The Cytochrome be-f Complex Connects
Photosystem
II to
Photosystem
I
791
Photosystem
I Carries Out the Second Charge-Separation
Step in the
Z
Scheme
792
The
Chloroplast ATP
Synthase Uses the Proton Gradient
Generated by the Photosynthetic Light Reactions to
Produce ATP
793
All Photosynthetic Reaction Centers Have Evolved From
a Common Ancestor
793
The Proton-Motive Force for ATP Production in Mitochondria
and Chloroplasts Is Essentially the Same
794
Chemiosmotic Mechanisms Evolved in Stages
794
By Providing an Inexhaustible Source of Reducing Power,
Photosynthetic Bacteria Overcame a Major Evolutionary
Obstacle
796
The Photosynthetic Electron-Transport Chains of Cyanobacteria
Produced Atmospheric Oxygen and Permitted New
Life-Forms
796
Summary
798
THE GENETIC SYSTEMS OF MITOCHONDRIA AND
CHLOROPLASTS
800
The Genetic Systems of Mitochondria and Chloroplasts Resemble
Those of Prokaryotes
800
Over Time, Mitochondria and Chloroplasts Have Exported Most
of Their Genes to the Nucleus by Gene Transfer
801
The Fission and Fusion of Mitochondria Are Topologlcally
Complex Processes
802
Animal Mitochondria Contain the Simplest Genetic Systems
Known
803
Mitochondria Have a Relaxed Codon Usage and Can Have a
Variant Genetic Code
804
Chtoroplasts and Bacteria Share Many Striking Similarities
806
Organelle
Genes Are Maternally Inherited in Animals and Plants
807
Mutations in Mitochondrial
DNA
Can Cause Severe Inherited
Diseases
807
The Accumulation of Mitochondrial
DNA
Mutations Is a
Contributor to Aging
808
Why Do Mitochondria and Chloroplasts Maintain a Costly
Separate System for
DNA
Transcription and Translation?
808
Summary
809
Problems
809
References
811
Chapter
15
Cell Signaling
813
PRINCIPLES OF CELL SIGNALING
813
Extracellular Signals Can Act Over Short or Long Distances
814
Extracellular Signal Molecules Bind to Specific Receptors
815
Each Cell Is Programmed to Respond to Specific Combinations
of Extracellular Signals
816
There Are Three Major Classes of Cell-Surface Receptor Proteins
818
Cell-Surface Receptors Relay Signals Via Infracellular Signaling
Molecules
819
intracellular Signals Must Be Specific and Precise in a Noisy
Cytoplasm
820
Intracelluiar Signaling Complexes Form at Activated Receptors
822
Modular Interaction Domains Mediate Interactions Between
Intracellular Signaling Proteins
822
The Relationship Between
Signa?
ana Response Varies in Different
Signaling Pathways
824
The Speed of a Response Depends en the Turnover of Signaling
Molecules
825
Ceils Can Respond Abruptly
io a
Gradually Increasing
Signai
827
Positive Feedback Can Generate an AU-c-r-None Response
828
Negative Feedback is a Common Motif in Signaling Systems
829
Cells Can Adjust Their Sensitivity
to a
Signa: 830
Summary
831
SIGNALING THROUGH G-PROTEIN-COUPLED RECEPTORS
832
Trimeric G Proteins
Relay Signals From GPCRs
832
Some
G Proteins
Regulate the Production of Cyclic AMP
833
Cyclic-AMP-Dependerrt Protein Kinase (PKA) Mediates Most
of the Effects of Cyclic AMP
834
Some
G Proteins
Signal Via Phospholipids
836
Ca2+ Functions as a Ubiquitous Intracellular Mediator
838
Feedback Generates
Ca24"
Waves and Oscillations
838
Ca2+/Calmodulin-Dependent Protein Kinases Mediate
Many Responses to
Ca2"1"
Signals
840
Some
G
Proteins Directly Regulate Ion Channels
843
Smell and Vision Depend on GPCRs That Regulate Ion Channels
843
Nitric Oxide Is a Gaseous Signaling Mediator That Passes
Between Cells
846
Second Messengers and Enzymatic Cascades Amplify
Signais
848
GPCR Desensitization Depends on Receptor Phosphorylation
848
Summary
849
SIGNALING THROUGH ENZYME-COUPLED RECEPTORS
850
Activated Receptor Tyrosine Kinases (RTKs) Phosphorylate
Themselves
850
Phosphorylated Tyroslnes on RTKs Serve as Docking Sites for
Intracellular Signaling Proteins
852
Proteins with SH2 Domains Bind to Phosphorylated Tyrosines
852
The GTPase
Ras
Mediates Signaling by Most RTKs
854
Ras
Activates a MAP Kinase Signaling Module
855
Scaffold Proteins Help Prevent Cross-talk Between Parallel
MAP Kinase Modules
857
Rho Family GTPases Functionally Couple Cell-Surface Receptors
to the Cytoskeleton
858
PI 3-Kinase Produces
Lipid
Docking Sites in the Plasma
Membrane
859
The PI-3-Kinase-Akt Signaling Pathway Stimulates Animal
Cells to Survive and Grow
860
RTKs and GPCRs Activate Overlapping Signaling Pathways
861
Some Enzyme-Coupled Receptors Associate with Cytoplasmic
Tyrosine Kinases
862
Cytoklne Receptors Activate the JAK-STAT Signaling Pathway
863
Protein Tyrosine Phosphatases Reverse Tyrosine Phosphorylations
864
Signal Proteins of the
TGFß Superfamily
Act Through Receptor
Serine/Threonine Kinases and Smads
865
Summary
866
ALTERNATIVE SIGNALING ROUTES IN GENE REGULATION
867
The Receptor Notch Is a Latent Transcription Regulatory Protein
867
Wnt Proteins Bind to Frizzled Receptors and Inhibit the
Degradation of
ß-Catenin 868
Hedgehog Proteins Bind to Patched. Relieving Its Inhibition of
Smoothened
871
Many Stressful and Inflammatory Stimuli Act Through an
NFicB-Dependent Signaling Pathway
873
Nuclear Receptors Are Ligand-Modulated Transcription
Regulators
874
Circadian Clocks Contain Negative Feedback Loops That
Control Gene Expression
876
Three Proteins in a Test Tube Can Reconstitute a Cyanobacterial
Circadian Clock
878
Summary
879
SIGNALING IN PLANTS
880
Multicellularity and Cell Communication Evolved Independently
in Plants and Animals
880
Receptor Serine,'Threonine Kinases Are the Largest Class of
Ceil-Surface Receptors in Plants
881
Ethylene
Blocks the Degradation of Specific Transcription
Regulator/ Proteins in the Nucleus
881
Regulated Positioning of Auxin Transporters Patterns Plant
Growth
882
Phytochromes Detect Red Light, and
Cryptochromes
Detect
Blue Light
" * 883
Summary
885
Problems
886
References
887
Chapter
16
The Cytoskeleton
889
FUNCTION AND ORIGIN OF THE CYTOSKELETON
889
Cytosketeta! Filaments Adapt to Form Dynamic or Stable
Structures
890
Тле
Cytoskeleton Determines Cellular Organization and Polarity
892
Filaments Assemble from Protein Subunits That Impart Specific
Physical and Dynamic Properties
893
xxx
DETAILED CONTENTS
Accessory Proteins and Motors Regulate Cytoskeletal Filaments
Bacterial Cell Organization and Division Depend on Homologs
of Eukaryotic Cytoskeletal Proteins
Summary
ACTIN AND ACTIN-BINDING PROTEINS
Actin Submits Assemble Head-to-Tail to Create Flexible, Polar
Filaments
_
Nucleate Is the Rate-Limiting Step in the Formation of Actin
Filaments
Actin Filaments Have Two Distinct Ends That Grow at Different
Rates
ATP Hydrolysis Within Actin Filaments Leads to Treadmilling at
Steady State
The Functions of Actin Filaments Are Inhibited by Both Polymer-
stabilizing and Polymer-destabilizing Chemicals
Actin-Binding Proteins Influence Filament Dynamics and
Organization
Monomer Availability Controls Actin Filament Assembly
Actln-Nucleating Factors Accelerate Polymerization and
Generate Branched or Straight Filaments
Actin-Filament-Binding Proteins Alter Filament Dynamics
Severing Proteins Regulate Actin Filament Depolymerization
Higher-Order Actin Filament Arrays Influence Cellular
Mechanical Properties and Signaling
Bacteria Can Hijack the Host Actin Cytoskeleton
Summary
MYOSIN AND ACTIN
Actin-Based Motor Proteins Are Members of the Myosin
Superfamily
Myosin Generates Force by Coupling ATP Hydrolysis to
Conformatíoi íal
Changes
Sliding of Myosin II Along Actin Filaments Causes Muscles
to Contract
A Sudden Rise in Cytosolic Ca'1* Concentration Initiates
Muscle Contraction
Heart Muscle Is a Precisely Engineered Machine
Actin and Myosin Perform a Variety of Functions in Non-Muscle
Cells
Summary
894
896
898
899
900
901
904
904
906
906
907
909
911
913
914
915
915
916
916
920
923
923
925
925
926
927
MICROTUBULES
Microtubules Are Hollow Tubes Made of
Protofilaments
Microtubules Undergo Dynamic Instability
.
Microtubule Functions Are Inhibited by Both Polymer-stabilizing
and Polymer-destabilizing Drugs
929
A Protein Complex Containing y-Tubulin Nucleates Microtubules
929
Microtubules Emanate from the Gentrosome in Animal Cells
930
Microtubule-Binding Proteins Modulate Filament Dynamics
and Organization
932
Microtubule Plus-End-Binding Proteins Modulate Microtubule
Dynamics and Attachments
932
Tubulin-Sequestering and Microtubule-Severing Proteins
Destabilize Microtubules
935
Two Types of Motor Proteins Move Along Microtubules
936
Microtubules and Motors Move
Organelies
and Vesicles
938
Construction of Complex Microtubule Assemblies Requires
Microtubule Dynamics and Motor Proteins
940
Motile Cilia and
Flagella Are
Built from Microtubules and Dyneins
941
Primaj
Cilia Perform Important Signaling Functions in
Animal Cells
942
Summary
943
INTERMEDIATE FILAMENTS AND SEPTINS
944
Intermediate Filament Structure Depends on the Lateral Bundling
and Twisting of Coileti-Coite
" 945
Intermediate Filaments Impart Mechanical Stability to
Animai
Cells
946
Linker Proteins Connect Cytoskeietal Filaments and Bridge the
Nuclear Envelope
948
Septins Form Filaments That Regulate Cell Pofarity
949
Summary
"
g50
CELL POLARIZATION AND MIGRATION
951
Many Cells Can Crawl Across a Solid Substratum
951
Actin Polymerization Drives Plasma Membrane Protrusion
951
Lamelüpodta
Contam
Ail of the Machinery Required for Cell Motility
953
Myosin Contraction and
Cel!
Adhesion Allow Cells to Pull
Themselves Forward g54
Cell Polarization Is Controlled by Members of the Rho Protein
Family
955
Extracellular Signals Can Activate the Three Rho Protein Family
Members
958
External Signals Can Dictate the Direction of Cell Migration
958
Communication Among Cytoskeletal Elements Coordinates
Whole-Cell Polarization and Locomotion
959
Summary
960
Problems
960
References
962
Chapter
17
The Cell Cycle
963
OVERVIEW OF THE CELL CYCLE
963
The Eukaryotic Cell Cycle Usually Consists of Four Phases
964
Cell-Cycle Control Is Similar in All Eukaryotes
965
Cell-Cycle Progression Can Be Studied in Various Ways
966
Summary
967
THE CELL-CYCLE CONTROL SYSTEM
967
The Cell-Cycle Control System Triggers the Major Events of
the Cell Cycle
967
The Cell-Cycle Control System Depends on Cyclically Activated
Cyclin-Dependent Protein Kinases (Cdks)
968
Cdk Activity Can Be Suppressed By Inhibitory Phosphorylation
and Cdk Inhibitor Proteins (CKIs)
970
Regulated Proteolysis Triggers the Metaphase-to-Anaphase
Transition
970
Cell-Cycle Control Also Depends on Transcriptional Regulation
971
The Cell-Cycle Control System Functions as a Network of
Biochemical Switches
972
Summary
974
S
PHASE
974
S-Cdk Initiates
DNA
Replication Once Per Cycle
974
Chromosome Duplication Requires Duplication of Chromatin
Structure
975
Cohesins Hold Sister Chromatids Together
977
Summary
977
MITOSIS
978
M-Cdk Drives Entry Into Mitosis
978
Dephosphorylation Activates M-Cdk at the Onset of Mitosis
978
Condensin Helps Configure Duplicated Chromosomes for
Separation
979
The Mitotic Spindle Is a Microtubule-Based Machine
982
Microtubule-Dependent Motor Proteins Govern Spindle
Assembly and Function
983
Multiple Mechanisms Collaborate in the Assembly of a Bipolar
Mitotic Spindle
984
Centrosome Duplication Occurs Early in the Cell Cycle
984
M-Cdk Initiates Spindle Assembly in
Prophase
985
The Completion of Spindle Assembly in Animal Cells Requires
Nuclear-Envelope Breakdown
985
Microtubule Instability Increases Greatly in Mitosis
986
Mitotic Chromosomes Promote Bipolar Spindle Assembly
986
Kinetochores Attach Sister Chromatids to the Spindle
987
Bi-orientation Is Achieved by Trial and Error
988
Multiple Forces Act on Chromosomes in the Spindle
990
The APC/C Triggers Sister-Chromatid Separation and the
Completion of Mitosis
992
Unattached Chromosomes Block Sister-Chromatid Separation:
The Spindle Assembly Checkpoint
993
Chromosomes Segregate in
Anaphase
A and
В
994
Segregated Chromosomes Are Packaged in Daughter Nuclei
atTelophase ~
' 995
Summary
995
CYTOKINESIS
996
Actin and Myosin II in the Contractile Ring Generate the Force
for Cytokinesis
996
Local Activation of RhoA Triggers Assembly and Contraction
of the Contractile Ring
997
The Microtubules of the Mitotic Spindle Determine the Plane
of Animal Ceil Division
997
The Phragmoplast Guides Cytokinesis in Higher Plants
1000
Membrane-Enclosed Organelles Must Be Distributed to
Daughter Cells During Cytokinesis
1001
DETAILED CONTENTS
XXXI
Some Cells Reposition Their Spindle to Divide Asymmetrically
1001
Mitosis Can Occur Without Cytokinesis
1002
The
Gì
Phase Is a Stable State of Cdk Inactivity
1002
Summary
1004
MEIOSIS
1004
Meiosis Includes Two Rounds of Chromosome Segregation
1004
Duplicated Homologs Pair During Meiotic
Prophase
1006
Homolog
Pairing Culminates in the Formation of a Synaptonemal
Complex
1006
Homolog
Segregation Depends on Several Unique Features
of Meiosis I
1008
Crossing-Over Is Highly Regulated
1009
Meiosis Frequently Goes Wrong
1010
Summary
1010
CONTROL OF CELL DIVISION AND CELL GROWTH
1010
Mitogens Stimulate Cell Division
1011
Cells Can Enter a Specialized Nondividing State
1012
Mitogens Stimulate GrCdk and Gi/S-Cdk Activities
1012
DNA
Damage Blocks Cell Division: The
DNA
Damage Response
1014
Many Human Cells Have a Built-in Limitation on the Number
of Times They Can Divide
1016
Abnormal Proliferation Signals Cause Cell-Cycle Arrest or
Apoptosis, Except in Cancer Cells
1016
Cell Proliferation is Accompanied by Cell Growth
1016
Proliferating Cells Usually Coordinate Their Growth and Division
1018
Summary
1018
Problems
1019
References
1020
Chapter
18
Cell Death
1021
Apoptosis Eliminates Unwanted Cells
1021
Apoptosis Depends on an tntracellular Proteolytic Cascade
That Is Mediated by Caspases
1022
Cell-Surface Death Receptors Activate the Extrinsic Pathway
of Apoptosis
1024
The Intrinsic Pathway of Apoptosis Depends on Mitochondria
1025
Bcl2 Proteins Regulate the Intrinsic Pathway of Apoptosis
1025
lAPs Help Control Caspases
1029
Extracellular Survival Factors Inhibit Apoptosis in Various Ways
1029
Phagocytes Remove the Apoptotic Cell
1030
Either Excessive or Insufficient Apoptosis Can Contribute to
Disease
1031
Summary
1032
Problems
1033
References
1034
Chapter
19
Cell Junctions and the Extracellular
Matrix
1035
CELL-CELL JUNCTIONS
1038
Cadherins Form a Diverse Family of Adhesion Molecules
1038
Cadnerins Mediate Homopnilic Adhesion
1038
Cadherin-Dependent Cell-Cell Adhesion Guides the
Organization of Developing Tissues
1040
Epithelial-Mesencnymal Transitions Depend on Control of
Cadherins
1042
Catenins Link
Classica!
Cadherins to the Acfc Cytosfceieton
1042
Adnerens Junctions Respond to Forces Generated by the Actin
Cytoskeleion
1Ö42
Tissue Remodeling
Depenas
en
íř.e
Coordination
ď
Acîin-
Mediated
Contracte1
Witt".
Ceíi-Ceii
Aonescn
1043
Desmoscmes
Give
Epitnsia
Mecťan.cal
Strengin 1045
T¡gní
Junctions Form a Sea; Bet.·.
een
Ce's
ъг.й
a Fence
Between Plasma
Memorane
Dcrans
1047
Tsght Junctions Contain Siraras
čí T^arsmernbíars
Adhesion
Proteins
1047
Scaffod Proteins Organize
Juncťona! Protein
Complexes
1049
Gac Junctions Couoie
Ceüs
Bctn Eiectncany and
Metabolica!!*/
1050
A Gap-Junction Connexon is Maae oT'
Sx
TransTTsmbrane
Connextn Subumts
1051
■ъ
Plants. Plasmodesmata Perform
Магл
of
tne
Same Functions
as
Gao
Junctions
1053
Seiectms Mediate Transient Ceii-Ceii Adnesions in the
Bloodstream
1054
Members of the Immunoglobulin Superfamily Mediate
Ca2+-lndependent Cell-Cell Adhesion
1055
Summary
1056
THE EXTRACELLULAR MATRIX OF ANIMALS
1057
The Extracellular Matrix Is Made and Oriented by the Cells
Within It
1057
Glycosaminoglycan (GAG) Chains Occupy Large Amounts of
Space and Form
Hydrated Gels 1058
Hyaluronan Acts as a Space Filler During Tissue Morphogenesis
and Repair
1059
Proteoglycans Are Composed of GAG Chains Covalently
Linked to a Core Protein
1059
Collagens
Are the Major Proteins of the Extracellular Matrix
1061
Secreted Fibril-Associated
Collagens
Help Organize the Fibrils
1063
Cells Help Organize the Collagen Fibrils They Secrete by
Exerting Tension on the Matrix
1064
Elastin Gives Tissues Their Elasticity
1065
Fibronectin and Other Multidomain Glycoproteins Help
Organize the Matrix
1066
Fibronectin Binds to
Integrins
1067
Tension Exerted by Cells Regulates the Assembly of
Fibronectin Fibrils
1068
The Basal Lamina Is a Specialized Form of Extracellular Matrix
1068
Laminin and Type IV Collagen Are Major Components of the
Basal Lamina
1069
Basal Laminae Have Diverse Functions
1070
Cells Have to Be Able to Degrade Matrix, as Well as Make It
1072
Matrix Proteoglycans and Glycoproteins Regulate the
Activities of Secreted Proteins
1073
Summary
1074
CELL-MATRIX JUNCTIONS
1074
Integrins
Are
Transmembrane Heterodimers
That Link the
Extracellular Matrix to the Cytoskeleton
1075
Integrin
Defects Are Responsible for Many Genetic Diseases
1076
Integrins
Can Switch Between an Active and an Inactive
Conformation
1077
Integrins
Cluster to Form Strong Adhesions
1079
Extracellular Matrix Attachments Act Through
Integrins
to
Control Cell Proliferation and Survival
1079
Integrins
Recruit Intracellular Signaling Proteins at Sites of
Cell-Matrix Adhesion
1079
Cell-Matrix Adhesions Respond to Mechanical Forces
1080
Summary
1081
THE PLANT CELL WALL
1081
The Composition of the Cell Wall Depends on the Cell Type
1082
The Tensile Strength of the Cell Wall Allows Plant Cells to
Develop
Turgor
Pressure
1083
The Primary Cell
Wali
Is Built from Cellulose Microfibrils
Interwoven with a Network of Pectic Polysaccharides
1083
Oriented Cell Wall Deposition Controls Plant Cell Growth
1085
Microtubules Orient Cell Wall Deposition
1086
Summary
1087
Problems
1087
References
1089
Chapter
20
Cancer
1091
CANCER AS A MICROEVOLUTIONARY PROCESS
1091
Cancer Ceiis Bypass Normal Proliferation
Contrais
and
Colonize Other Tissues
1092
Most Cancers Derive from a Single Abnormal Gel!
1093
Cancer Ceiis Contain Somatic Mutations
1094
A Singte Mutation is Not Enough to Change a Normal Cell
into a Cancer Cell
1094
Cancers Develop Gradual/ from tncreasingiy Aberrant Ceiis
1095
Tumor Progression Involves Successive Rounds of Random
inherited Change Followed by Natural Selection
1096
Human Cancer Celts Are Genetically Unstable
1097
Cancer Ceiis Display an Altered Control of Growth
1098
Cancer
Ceüs
Have an Altered Sugar Metabolism
1098
Cancer Cells Have an Abnormal Ability to Survive Stress and
DNA
Damage
1099
Human Cancer Ceiis Escape a Built-in Limit to Cell Proliferation
1099
The Tumor Microenvtronment influences Cancer Development
1100
xxxii
DETAILED CONTENTS
Cancer Cells Must Survive and Proliferate in a Foreign
Environment H01
Many Properties Typically Contribute to Cancerous Growth
1103
Summary
ПОЗ
CANCER-CRITICAL GENES: HOW THEY ARE FOUND
AND WHAT THEY DO
1104
The Identification of Gain-of-Function and Loss-of-Function
Cancer Mutations Has Traditionally Required Different
Methods
1104
Retroviruses Can Act as Vectors for Oncogenes That Alter Cell
Behavior
1105
Different Searches for Oncogenes Converged on the Same
Gene-Ras
1106
Genes Mutated in Cancer Can Be Made Overactive in Many
Ways
1106
Studies of Rare Hereditary Cancer Syndromes First Identified
Tumor Suppressor Genes
1107
Both Genetic and Epigenetic Mechanisms Can Inactivate
Tumor Suppressor Genes
1108
Systematic Sequencing of Cancer Cell Genomes Has
Transformed Our Understanding of the Disease
1109
Many Cancers Have an Extraordinarily Disrupted Genome
1111
Many Mutations in Tumor Cells are Merely Passengers
1111
About One Percent of the Genes in the Human Genome Are
Cancer-Critical
1112
Disruptions in a Handful of Key Pathways Are Common to
Many Cancers
1113
Mutations in the
РІЗК
/'Akt/mTOR
Pathway Drive Cancer Cells
to Grow
1114
Mutations in the p53 Pathway Enable Cancer Cells to Survive
and Proliferate Despite Stress and
DNA
Damage
1115
Genome Instability Takes Different Forms In Different Cancers
1116
Cancers of Specialized Tissues Use Many Different Routes to
Target the Common Core Pathways of Cancer
1117
Studies Using Mice Help to Define the Functions of Cancer-
Critical Genes
1117
Cancers Become More and More Heterogeneous as They
Progress
1118
The Changes in Tumor Cells That Lead to Metastasis Are
Still Largely a Mystery
1119
A Small Population of Cancer Stem Cells May Maintain Many
Tumors
1120
The Cancer Stem-Cell Phenomenon Adds to the Difficulty
of Curing Cancer
1121
Colorectal Cancers Evolve Siowly
Vìa a
Succession of Visible
Changes
1122
A Few Key Genetic Lesions Are Common to a Large Fraction
of Colorectal Cancers
1123
Some Colorectal Cancers Have Defects in
DNA
Mismatch Repair
1124
The Steps of Tumor Progression Can Often Be Correlated
with Specific Mutations
1125
Summary
1126
CANCER PREVENTION AND TREATMENT: PRESENT AND
FUTURE
Epidemiology Reveals That Many Cases of Cancer Are
Preventable
Sensitive Assays Can Detect Those Cancer-Causing Agents
that Damage
DNA
Fifty Percent of Cancers Could Be Prevented by Changes
in Lifestyle
Viruses and Other Infections Contribute to a Significant
Proportion of Human Cancers
Cancers of the Uterine Cervix Can Be Prevented by Vaccination
Against Human
Papiîlomavirus
Infectious Agents Can Cause Cancer in a Variety of Ways
The Search for Cancer Cures Is Difficult but Not Hopeless
Traditional Therapies Exploit the Genetic Instability and Loss
of Ceil-Cycle Checkpoint Responses in Cancer Cells
New Drugs Can Kill Cancer Cells Selectively by Targeting
Specific Mutations
PARP Inhibitors Kill Cancer Cells That Have Defects in
Brea?
or Brca2 Genes
Small Molecules Can Be Designed to inhibit Specific
Oncogene
Proteins
1127
1127
1127
1128
1129
1131
1132
1132
1132
1133
1133
1135
Many Cancers May Be Treatable by Enhancing the Immune
Response Against the Specific Tumor
1137
Cancers Evolve Resistance to Therapies
1139
Combination Therapies May Succeed Where Treatments with
One Drug at a Time Fail
1139
We Now Have the Tools to Devise Combination Therapies
Tailored to the Individual Patient
1140
Summary
1141
Problems
1141
References
1143
Chapter
21
Development of Multicellular
Organisms
1145
OVERVIEW OF DEVELOPMENT
1147
Conserved Mechanisms Establish the Basic Animal Body Plan
1147
The Developmental Potential of Cells Becomes Progressively
Restricted
1148
Cell Memory Underlies Cell Decision-Making
1148
Several Model Organisms Have Been Crucial for Understanding
Development
1148
Genes Involved in Cell-Cell Communication and Transcriptionaf
Control Are Especially Important for Animal Development
1149
Regulatory
DNA
Seems Largely Responsible for the Differences
Between Animal Species
1149
Small Numbers of Conserved Cell-Cell Signaling Pathways
Coordinate Spatial Patterning
1150
Through Combinatorial Control and Cell Memory, Simple
Signals Can Generate Complex Patterns
1150
Morphogens
Are Long-Range Inductive Signals That Exert
Graded Effects
" 1151
Lateral Inhibition Can Generate Patterns of Different Cell Types
1151
Short-Range Activation and Long-Range Inhibition Can
Generate Complex Cellular Patterns
1152
Asymmetric Cell Division Can Also Generate Diversity
1153
Initial Patterns Are Established in Small Fields of Cells and
Refined by Sequential Induction as the Embryo Grows
1153
Developmental Biology Provides Insights into Disease and
Tissue Maintenance
1154
Summary
1154
MECHANISMS OF PATTERN FORMATION
11
55
Different Animals Use Different Mechanisms to Establish Their
Primary Axes of Polarization
1155
Studies in
Drosophila
Have Revealed the Genetic Control
Mechanisms Underlying Development
1157
Egg-Polarity Genes Encode Macromolecules Deposited in the
Egg to Organize the Axes of the Early
Drosophila
Embryo
1157
Three Groups of Genes Control
Drosophila
Segmentation Along
the
А
-P
Axis
1159
A Hierarchy of Gene Regulatory Interactions Subdivides the
Drosophila
Embryo
1159
Egg-Polarity, Gap, and Pair-Rule Genes Create a Transient
Pattern That Is Remembered by Segment-Polarity and
Hox Genes ^
116°
Hox Genes Permanently Pattern the
А
-P
Axis 1162
Hox Proteins Give Each Segment Its Individuality
11
63
Hox Genes Are Expressed According to Their Order in the
Hox Complex
1163
Trithorax and Polycomb Group Proteins Enable the Hox
Complexes to Maintain a Permanent Record of Positional
Information
1164
The D-V Signaling Genes Create a Gradient of the Transcription
Regulator Dorsal 1164
A Hierarchy of Inductive Interactions Subdivides the Vertebrate
Embryo 1166
A Competition Between Secreted Signaling Proteins Patterns
the Vertebrate Embryo
"
1168
The Insect Dorsoventral Axis Corresponds to the Vertebrate
Ventral-Dorsal Axis
1169
Hox Genes Control the Vertebrate
А
-P
Axis 1169
Some Transcription Regulators Can Activate a Program That
Defines a Cell Type or Creates an Entire Organ
11
70
Notch-Mediated Lateral Inhibition Refines Cellular Spacing
Patterns
1171
DETAILED CONTENTS
xxxiii
Asymmetric Cell Divisions Make Sister Cells Different
1173
Differences in Regulatory
DNA
Explain Morphological Differences
1174
Summary
1175
DEVELOPMENTAL TIMING
1176
Molecular Lifetimes Play a Critical Part in Developmental Timing
1176
A Gene-Expression Oscillator Acts as a Clock to Control
Vertebrate Segmentation
1177
Intracellular Developmental Programs Can Help Determine
the Time-Course of a Cell's Development
1179
Cells Rarely Count Cell Divisions to Time Their Development
1180
MicroRNAs Often Regulate Developmental Transitions
1180
Hormonal Signals Coordinate the Timing of Developmental
Transitions
1182
Environmental Cues Determine the Time of Flowering
1182
Summary
1184
MORPHOGENESIS
1184
Cell Migration Is Guided by Cues in the Cell's Environment
1185
The Distribution of Migrant Cells Depends on Survival Factors
1186
Changing Patterns of Cell Adhesion Molecules Force Cells
Into New Arrangements
1187
Repulsive Interactions Help Maintain Tissue Boundaries
1188
Groups of Similar Cells Can Perform Dramatic Collective
Rearrangements
1188
Planar Cell Polarity Helps Orient Cell Structure and Movement in
Developing Epithelia
1189
Interactions Between an Epithelium and Mesenchyme Generate
Branching Tubular Structures
1190
An Epithelium Can Bend During Development to Form a Tube
or Vesicle
" 1192
Summary
1193
GROWTH
1193
Tlie
Proliferation. Death, and Size of Cells Determine Organism
Size
* 1194
Animals and Organs Can Assess and Regulate Total Cell Mass
1194
Extracellular Signals Stimulate or Inhibit Growth
1196
Summary
1197
NEURAL DEVELOPMENT
1198
Neurons Are Assigned Different Characters According to the
Time and Place of Their Birth
1199
The Growth Cone Pilots
Axons
Along Specific Routes Toward
Their Targets
' 1201
A Variety of Extracellular Cues Guide
Axons
to their Targets
1202
The Formation of Orderly Neural Maps Depends on
Neuronal
Specificity
1204
Both
Dendrites
and Axonal Branches From the Same Neuron
Avoid One Another
1206
Target Tissues Release Neurotrophlc Factors That Control
Nerve Cell Growth and Survival
1208
Formation of Synapses Depends on Two-Way Communication
Between Neurons and Their Target Cells
1209
Synaptic Pruning Depends on Electrical Activity and Synaptic
Signaling
1211
Neurons That Fire Together Wire Together
1211
Summary
1213
Problems
1213
References
1215
Chapter
22
Stem Cells and Tissue Renewal
1217
STEM CELLS AND RENEWAL IN EPITHELIAL TISSUES
1217
Tee Lining of the Srrai; iries£r.e (s
Ccni^uail;
Rer.s.ved
Through
Cel
Pre: feratän r,
:f.s
Сг.
p:s
' 121
3
Stem Ceils
о?
the
Ѕппа;'
Iriisstr-e
Le ai
zi Nsar
+ће
Base
oí
EacnCryot
1219
The
Тло
Daughters cf
a Ster.
Cs
:
Fscs
s
Сѓзсе
1219
Wc! &gr,aiing
Mantara me
G-j: Ster-Ce^
Ccrcartrrent
1220
Sîem Cefe
at
îhe CrvDî
Base Are VUtcoìe^i.
Gtvirg
Rse io
the
Fuli
Range
cf
Differentiated
'ntesí.nai
Сен
Types
1220
Тне Тло
Daugnte's of a
Ster*
Ce.
Do
Not
Алауѕ
have to
Become Different
1222
pane№ Cells Create
tne Ste^-Ce'1
Nicne
1222
A Single Lgo-expressing
Cei'
·η
Cinture
Can Generate an Entire
Organized Crypt-Villus System
1223
Ephrin-Eph Signaling Drives Segregation of the Different Gut
Cell Types
" 1224
Notch Signaling Controls Gut Cell Diversification and Helps
Maintain the Stem-Cell State
1224
The Epidermal Stem-Cell System Maintains a Self-Renewing
Waterproof Barrier
1225
Tissue Renewal That Does Not Depend on Stem Cells: Insulin-
Secreting Cells in the Pancreas and Hepatocytes in the Liver
1226
Some Tissues Lack Stem Cells and Are Not Renewable
1227
Summary
1227
FIBROBLASTS
AND THEIR TRANSFORMATIONS:
THE CONNECTIVE-TISSUE CELL FAMILY
Fibroblasts
Change Their Character in Response to Chemical
and Physical Signals
Osteoblasts Make Bone Matrix
Bone Is Continually Remodeled by the Cells Within It
Osteoclasts Are Controlled by Signals From Osteoblasts
Summary
GENESIS AND REGENERATION OF SKELETAL MUSCLE
Myoblasts Fuse to Form New Skeletal Muscle Fibers
Some Myoblasts Persist as Quiescent Stem Ceils in the Adult
Summary
1228
1228
1229
1230
1232
1232
1232
1233
1234
1235
BLOOD VESSELS, LYMPHATICS, AND ENDOTHELIAL CELLS
1235
Endothelial Cells Line All Blood Vessels and Lymphatics
1235
Endothelial Tip Cells Pioneer Angiogenesis
1236
Tissues Requiring a Blood Supply Release VEGF
1237
Signals from Endothelial Cells Control Recruitment of Pericytes
and Smooth Muscle Cells to Form the Vessel Wall
1238
Summary
1238
A HIERARCHICAL STEM-CELL SYSTEM: BLOOD CELL
FORMATION
1239
Red Blood Cells Are All Alike; White Blood Cells Can Be
Grouped in Three Main Classes
1239
The Production of Each Type of Blood Cell in the Bone Marrow
Is
li idividually
Controlled
1240
Bone Marrow Contains
Multipotent
Hematopoietic Stern Cells,
Able to Give Rise to All Classes of Blood Cells
1242
Commitment Is a Stepwise Process
1243
Divisions of Committed Progenitor Cells Amplify the Number of
Specialized Blood Cells
1243
Stem Cells Depend on Contact Signals From
Stremai
Cells
1244
Factors That Regulate Hematopoiesis Can Be Analyzed in Culture
1244
Erythropoiesis Depends on the Hormone Erythrapoietin
1244
Multiple CSFs Influence Neutrophil and
Macrophage
Production
1245
The Behavior of a Hematopoietic Cell Depends Partly on Chance
1245
Regulation of Cell Survival Is as Important as Regulation of Cell
Proliferation
1246
Summary
1247
REGENERATION AND REPAIR
1247
Planarian
Worms Contain Stem Cells That Can Regenerate a
Whole New Body
1247
Some Vertebrates Can Regenerate Entire Organs
1248
Stem Cells Can Be Used Artificially to Replace
Ceüs
That Are
Diseased or Lost: Therapy for Blood and Epidermis
1249
Neura! Stem Ceils Can Be Manipulated in Culture and Used to
Repopulate
the Central Nervous System
1250
Summary
1251
CELL
REPROGRAMMING
AND PLURIPOTENT STEM CELLS
1251
Nuclei Can Be Reprcgrammed by Transplantation into Foreign
Cytoplasm
1252
Reprogramming of a Transplanted Nuc'eus involves Drastic
Epigenetic Changes
1252
Embryonic Stem
íESí
Cefe
Can Generate Any Part of
ine Body
1253
A Core Set of Transcription Regulators Defines and Maintains
the
ES
Ceil State
' 1254
Fibre-blasts Can Be Reprograrnmed to Create Induced
Piuripcient Stem Cells «PS
Celisi
1254
Reprogramming Involves a Massive Upheaval of the Gene
Centra! System
1255
An Experimental Manipulation of Factors that Modify Chromatin
Can increase Reprogramming Efficiencies
1256
ES
and ¡PS Ceils Can Be Guided to Generate Specific Adult
Ceil Types and Even Wncie Organs
1256
xxxiv
DETAILED
CONTENTS
Cells of One Specialized Type Can Be Forced to
Transdifferentiate Directly Into Another
1258
ES
and iPS Cells Are Useful for Drug Discovery and Analysis
of Disease
1258
Summary
1260
Problems
1260
References
1262
Chapter
23
Pathogens and Infection
1263
INTRODUCTION TO PATHOGENS AND THE HUMAN
MICROBIOTA
1263
The Human Microbiota Is a Complex Ecological System That Is
Important for Our Development and Health
1264
Pathogens Interact with Their Hosts in Different Ways
1264
Pathogens Can Contribute to Cancer, Cardiovascular Disease,
and Other Chronic Illnesses
1265
Pathogens Can Be Viruses, Bacteria, or Eukaryotes
1266
Bacteria Are Diverse and Occupy a Remarkable Variety of
Ecological Niches
1267
Bacterial Pathogens Carry Specialized Virulence Genes
1268
Bacterial Virulence Genes Encode Effector Proteins and Secretion
Systems to Deliver Effector Proteins to Host Cells
1269
Fungal and Protozoan Parasites Have Complex Life Cycles
Involving Multiple Forms
1271
All Aspects of Viral Propagation Depend on Host Cell Machinery
1273
Summary
1275
CELL BIOLOGY OF INFECTION
1276
Pathogens Overcome Epithelial Barriers to Infect the Host
1276
Pathogens That Colonize an Epithelium Must Overcome Its
Protective Mechanisms
1276
Extracellular Pathogens Disturb Host Cells Without Entering
Them
1277
Intracelular
Pathogens Have Mechanisms for Both Entering
and Leaving Host Cells
1278
Viruses Bind to Virus Receptors at the Host Cell Surface
1279
Viruses Enter Host Cells by Membrane Fusion, Pore Formation,
or Membrane Disruption
1280
Bacteria Enter Host Cells by Phagocytosis
1281
Intracellular Eukaryotic Parasites Actively Invade Host Cells
1282
Some Intracellular Pathogens Escape from the Phagosome
into the Cytosol
1284
Many Pathogens Alter Membrane Traffic in the Host Cell to
Survive and Replicate
1284
Viruses and Bacteria Use the Host-Cell Cytoskeleton for
Intracellular Movement
1286
Viruses Can Take Over the Metabolism of the Host Cell
1288
Pathogens Can Evolve Rapidly by Antigenic Variation
1289
Error-Prone Replication Dominates Viral Evolution
1291
Drug-Resistant Pathogens Are a Growing Problem
1291
Summary
1294
Problems
1294
References
1296
OVERVIEW OF THE ADAPTIVE IMMUNE SYSTEM
В
Cells Develop in the Bone Marrow,
Τ
Cells in the
Thymus
Immunological Memory Depends On Both Clonal Expansion
and Lymphocyte Differentiation
Lymphocytes Continuously Recirculate Through Peripheral
Lymphoid Organs
Immunological Self-Tolerance Ensures That
В
and
Τ
Cells
Do Not Attack Normal Host Cells and Molecules
Summary
1307
1308
1309
1311
1313
1315
1315
В
CELLS AND IMMUNOGLOBULINS
В
Cells Make Immunoglobulins (Igs) as Both Cell-Surface
Antigen Receptors and Secreted Antibodies
1315
Mammals Make Five Classes of Igs
1316
Ig
Light and Heavy Chains Consist of Constant and Variable
Regions
1318
Ig
Genes Are Assembled From Separate Gene Segments
During
В
Cell Development
1319
Antigen-Driven Somatic Hypermutatlon Fine-Tunes Antibody
Responses
1321
В
Cells Can Switch the Class of
lg
They Make
1322
Summary
1323
Τ
CELLS AND MHC PROTEINS
1324
Τ
Cell Receptors (TCRs) Are Ig-like Heterodimers
1325
Activated Dendritic Cells Activate Naive
Τ
Cells
1326
Τ
Cells Recognize Foreign Peptides Bound to MHC Proteins
1326
MHC Proteins Are the Most Polymorphic Human Proteins
Known
' 1330
CD4 and CD8 Co-receptors on
Τ
Cells Bind to Invariant Parts
of MHC Proteins
1331
Developing Thymocytes Undergo Negative and Positive Selection
1332
Cytotoxic
Τ
Cells Induce Infected Target Cells to Kill Themselves
1333
Effector Helper
Τ
Cells Help Activate Other Cells of the Innate
and Adaptive Immune Systems
1335
Naïve
Helper
Τ
Cells Can Differentiate Into Different Types of
Effector
Τ
Cells
1335
Both
Τ
and
В
Cells Require Multiple Extracellular Signals For
Activation
* 1336
Many Cell-Surface Proteins Belong to the
Ig Superfamlly 1338
Summary
1339
Problems
1340
References
1342
Glossary
Index
Tables
1:1
Chapter
24
The innate and Adaptive Immune
Systems
1297
THE INNATE IMMUNE SYSTEM
1298
Epithelial Surfaces Serve as Barriers to Infection
1298
Pattern Recognition Receptors (PRRs) Recognize Conserved
Features of Pathogens
1298
There Are Multiple Classes of PRRs
1299
Activated PRRs Trigger an Inflammatory Response at Sites of
Infection
1300
Phagocytic Cells Seek. Engulf, and Destroy Pathogens
1301
Complement Activation Targets Pathogens for Phagocytosis
or Lysis
1302
Virus-Infected Cells Take Drastic Measures to Prevent Viral
Replication
1303
Natural Killer Cells Induce Virus-Infected Cells to Kill Themselves
1304
Dendritic Cells Provide the Link Between the Innate and
Adaptive Immune Systems
1305
Summary
1305 |
| any_adam_object | 1 |
| author | Alberts, Bruce 1938- Johnson, Alexander 1968- Lewis, Julian 1946-2014 Morgan, David 1958- Raff, Martin 1938- Roberts, Keith 1945- Walter, Peter 1954- |
| author_GND | (DE-588)111053013 (DE-588)1089764340 (DE-588)1130342948 (DE-588)173873553 (DE-588)1130334937 (DE-588)1130343138 (DE-588)1130343545 |
| author_facet | Alberts, Bruce 1938- Johnson, Alexander 1968- Lewis, Julian 1946-2014 Morgan, David 1958- Raff, Martin 1938- Roberts, Keith 1945- Walter, Peter 1954- |
| author_role | aut aut aut aut aut aut aut |
| author_sort | Alberts, Bruce 1938- |
| author_variant | b a ba a j aj j l jl d m dm m r mr k r kr p w pw |
| building | Verbundindex |
| bvnumber | BV042185821 |
| callnumber-first | Q - Science |
| callnumber-label | QH581 |
| callnumber-raw | QH581.2 |
| callnumber-search | QH581.2 |
| callnumber-sort | QH 3581.2 |
| callnumber-subject | QH - Natural History and Biology |
| classification_rvk | WE 2400 WD 4150 WE 1000 WE 2401 |
| classification_tum | BIO 200f |
| ctrlnum | (OCoLC)900611205 (DE-599)BVBBV042185821 |
| dewey-full | 572.8 |
| dewey-hundreds | 500 - Natural sciences and mathematics |
| dewey-ones | 572 - Biochemistry |
| dewey-raw | 572.8 |
| dewey-search | 572.8 |
| dewey-sort | 3572.8 |
| dewey-tens | 570 - Biology |
| discipline | Biologie |
| edition | Sixth edition, international student edition |
| format | Book |
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| genre | 1\p (DE-588)4123623-3 Lehrbuch gnd-content |
| genre_facet | Lehrbuch |
| geographic | Altleiningen (DE-588)4001534-8 gnd Aphrodisias (DE-588)4002418-0 gnd |
| geographic_facet | Altleiningen Aphrodisias |
| id | DE-604.BV042185821 |
| illustrated | Illustrated |
| indexdate | 2024-09-26T10:00:55Z |
| institution | BVB |
| isbn | 9780815344322 9780815344643 |
| language | English |
| lccn | 014031818 |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-027624967 |
| oclc_num | 900611205 |
| open_access_boolean | |
| owner | DE-188 DE-29T DE-20 DE-91 DE-BY-TUM DE-578 DE-355 DE-BY-UBR DE-19 DE-BY-UBM DE-M49 DE-BY-TUM DE-B768 DE-11 DE-91G DE-BY-TUM DE-634 DE-29 DE-703 DE-83 DE-1050 DE-706 DE-573 |
| owner_facet | DE-188 DE-29T DE-20 DE-91 DE-BY-TUM DE-578 DE-355 DE-BY-UBR DE-19 DE-BY-UBM DE-M49 DE-BY-TUM DE-B768 DE-11 DE-91G DE-BY-TUM DE-634 DE-29 DE-703 DE-83 DE-1050 DE-706 DE-573 |
| physical | xxxiv, 1342, G34, I53, T1 Seiten Illustrationen, Diagramme |
| publishDate | 2015 |
| publishDateSearch | 2015 |
| publishDateSort | 2015 |
| publisher | Garland Science, Taylor & Francis Group |
| record_format | marc |
| spelling | Alberts, Bruce 1938- Verfasser (DE-588)111053013 aut Molecular biology of the cell Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts und Peter Walter The cell Sixth edition, international student edition New York, NY [u.a.] Garland Science, Taylor & Francis Group 2015 xxxiv, 1342, G34, I53, T1 Seiten Illustrationen, Diagramme txt rdacontent n rdamedia nc rdacarrier Cells Molecular Biology Cytologie (DE-588)4070177-3 gnd rswk-swf Zelle (DE-588)4067537-3 gnd rswk-swf Molekularbiologie (DE-588)4039983-7 gnd rswk-swf Altleiningen (DE-588)4001534-8 gnd rswk-swf Aphrodisias (DE-588)4002418-0 gnd rswk-swf 1\p (DE-588)4123623-3 Lehrbuch gnd-content Molekularbiologie (DE-588)4039983-7 s Cytologie (DE-588)4070177-3 s Zelle (DE-588)4067537-3 s 2\p DE-604 Aphrodisias (DE-588)4002418-0 g Altleiningen (DE-588)4001534-8 g 3\p DE-604 Johnson, Alexander 1968- Verfasser (DE-588)1089764340 aut Lewis, Julian 1946-2014 Verfasser (DE-588)1130342948 aut Morgan, David 1958- Verfasser (DE-588)173873553 aut Raff, Martin 1938- Verfasser (DE-588)1130334937 aut Roberts, Keith 1945- Verfasser (DE-588)1130343138 aut Walter, Peter 1954- Verfasser (DE-588)1130343545 aut Digitalisierung UB Regensburg - ADAM Catalogue Enrichment application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027624967&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 |
| spellingShingle | Alberts, Bruce 1938- Johnson, Alexander 1968- Lewis, Julian 1946-2014 Morgan, David 1958- Raff, Martin 1938- Roberts, Keith 1945- Walter, Peter 1954- Molecular biology of the cell Cells Molecular Biology Cytologie (DE-588)4070177-3 gnd Zelle (DE-588)4067537-3 gnd Molekularbiologie (DE-588)4039983-7 gnd |
| subject_GND | (DE-588)4070177-3 (DE-588)4067537-3 (DE-588)4039983-7 (DE-588)4001534-8 (DE-588)4002418-0 (DE-588)4123623-3 |
| title | Molecular biology of the cell |
| title_alt | The cell |
| title_auth | Molecular biology of the cell |
| title_exact_search | Molecular biology of the cell |
| title_full | Molecular biology of the cell Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts und Peter Walter |
| title_fullStr | Molecular biology of the cell Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts und Peter Walter |
| title_full_unstemmed | Molecular biology of the cell Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts und Peter Walter |
| title_short | Molecular biology of the cell |
| title_sort | molecular biology of the cell |
| topic | Cells Molecular Biology Cytologie (DE-588)4070177-3 gnd Zelle (DE-588)4067537-3 gnd Molekularbiologie (DE-588)4039983-7 gnd |
| topic_facet | Cells Molecular Biology Cytologie Zelle Molekularbiologie Altleiningen Aphrodisias Lehrbuch |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027624967&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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