Molecular biology of the cell:
Gespeichert in:
| Format: | Buch |
|---|---|
| Sprache: | English |
| Veröffentlicht: |
New York [u.a.]
Garland Science
2008
|
| Ausgabe: | 5. ed., reference ed. |
| Schlagworte: | |
| Online-Zugang: | Table of contents only Inhaltsverzeichnis |
| Beschreibung: | Getr. Zählung zahlr. Ill., graph. Darst. 1 DVD-ROM (12 cm) |
| ISBN: | 0815341113 9780815341116 |
Internformat
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| 245 | 1 | 0 | |a Molecular biology of the cell |c Bruce Alberts ... |
| 246 | 1 | 3 | |a The cell |
| 250 | |a 5. ed., reference ed. | ||
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| 650 | 7 | |a molecular biology |2 cabt | |
| 650 | 7 | |a Cells |2 cabt | |
| 650 | 7 | |a genetics |2 cabt | |
| 650 | 7 | |a molecular genetics |2 cabt | |
| 650 | 7 | |a signal transduction |2 cabt | |
| 650 | 7 | |a Biologia molecular |2 larpcal | |
| 650 | 7 | |a Citologia |2 larpcal | |
| 650 | 4 | |a Cytology | |
| 650 | 4 | |a Molecular biology | |
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Datensatz im Suchindex
| _version_ | 1804137294718828544 |
|---|---|
| adam_txt |
Contents
Special Features
Detailed Contents
Acknowledgments
A Note to the Reader
PART I INTRODUCTION TO THE CELL
1. Cells and Genomes
2. Cell Chemistry and Biosynthesis
3. Proteins
PART II BASIC GENETIC MECHANISMS
4. DNA, Chromosomes, and Genomes
5. DNA Replication, Repair, and Recombination
6. How Cells Read the Genome: From DNA to Protein
7. Control of Gene Expression
PART III METHODS
8. Manipulating Proteins, DNA, and RNA
9. Visualizing Cells
PART IV INTERNAL ORGANIZATION OF THE CELL
10. Membrane Structure
11. Membrane Transport of Small Molecules and the Electrical
Properties of Membranes
12. Intracellular Compartments and Protein Sorting
13. Intracellular Vesicular Traffic
14. Energy Conversion: Mitochondria and Chloroplasts
15. Mechanisms of Cell Communication
16. The Cytoskeleton
17. The Cell Cycle
18. Apoptosis
PART V CELLS IN THEIR SOCIAL CONTEXT
19. Cell Junctions, Cell Adhesion, and the Extracellular Matrix
20. Cancer
21. Sexual Reproduction: Meiosis, Germ Cells, and Fertilization
22. Development of Multicellular Organisms
23. Specialized Tissues, Stem Cells, and Tissue Renewal
24. Pathogens, Infection, and Innate Immunity
25. The Adaptive Immune System
Glossary
Index
Tables The Genetic Code, Amino Acids
viu
ix
xxvi
xxxi
1
45
125
195
263
329
411
501
579
617
651
695
749
813
879
965
1053
1115
1131
1205
1269
1305
1417
1485
1539
G-l
1-1
T-l
Special Features
Table 1-1 Some Genomes That Have Been Completely Sequenced
Table 1-2 The Numbers of Gene Families, Classified by Function, That Are Common to All
Three Domains of the Living World
Table 2-1 Covalent and Noncovalent Chemical Bonds
Table 2-2 The Types of Molecules That Form a Bacterial Cell
Table 2-3 Approximate Chemical Compositions of a Typical Bacterium and a Typical
Mammalian Cell
Table 2-4 Relationship Between the Standard Free-Energy Change, AG°, and the
Equilibrium Constant
Panel 2-1 Chemical Bonds and Groups Commonly Encountered in Biological Molecules
Panel 2-2 Water and Its Influence on the Behavior of Biological Molecules
Panel 2-3 The Principal Types of Weak Noncovalent Bonds that Hold Macromolecules
Together
Panel 2-4 An Outline of Some of the Types of Sugars Commonly Found in Cells
Panel 2-5 Fatty Acids and Other Lipids
Panel 2-6 A Survey of the Nucleotides
Panel 2-7 Free Energy and Biological Reactions
Panel 2-8 Details of the 10 Steps of Glycolysis
Panel 2-9 The Complete Citric Acid Cycle
Panel 3-1 The 20 Amino Acids Found in Proteins
Panel 3-2 Four Different Ways of Depicting a Small Protein, the SH2 Domain
Table 3-1 Some Common Types of Enzymes
Panel 3-3 Some of the Methods Used to Study Enzymes
Table 4-1 Some Vital Statistics for the Human Genome
Table 5-3 Three Major Classes of Transposable Elements
Table 6-1 Principal Types of RNAs Produced in Cells
Panel 8-1 Review of Classical Genetics
Table 10-1 Approximate Lipid Compositions of Different Cell Membranes
Table 11-1 A Comparison of Ion Concentrations Inside and Outside a Typical Mammalian Cell
Panel 11-2 The Derivation of the Nernst Equation
Panel 11-3 Some Classical Experiments on the Squid Giant Axon
Table 12-1 Relative Volumes Occupied by the Major Intracellular Compartments in a Liver
Cell (Hepatocyte)
Table 12-2 Relative Amounts of Membrane Types in Two Kinds of Eucaryotic Cells
Table 14-1 Product Yields from the Oxidation of Sugars and Fats
Panel 14-1 Redox Potentials
Table 15-5 The Ras Superfamily of Monomeric GTPases
Panel 16-2 The Polymerization of Actin and Tubulin
Panel 16-3 Accessory Proteins that Control the Assembly and Position of Cytoskeletal
Filaments
Table 17-2 Summary of the Major Cell-Cycle Regulatory Proteins
Panel 17-1 The Principle Stages of M Phase (Mitosis and Cytokinesis) in an Animal Cell
p. 18
p. 24
p. 53
p. 55
p. 63
p. 77
pp. 106-107
pp.108-109
pp. 110-111
pp. 112-113
pp. 114-115
pp. 116-117
pp. 118-119
pp. 120-121
pp. 122-123
pp.128-129
132-133
p. 159
162-163
p. 206
p. 318
p. 336
pp. 554-555
p. 624
p. 652
p. 670
p. 679
p. 697
p. 697
p. 824
p. 830
p. 926
pp. 978-979
pp.
pp.
pp. 994-995
p. 1066
pp. 1072-1073
Detailed Contents
Chapter 1 Cells and Genomes 1
THE UNIVERSAL FEATURES OF CELLS ON EARTH 1
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
The Fragment of Genetic Information Corresponding to One
Protein Is One 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 9
A Living Cell Can Exist with Fewer Than 500 Genes 10
Summary 11
THE DIVERSITY OF GENOMES AND THE TREE OF LIFE 11
Cells Can Be Powered by a Variety of Free Energy Sources 12
Some Cells Fix Nitrogen and Carbon Dioxide for Others 13
The Greatest Biochemical Diversity Exists Among Procaryotic Cells 14
The Tree of Life Has Three Primary Branches: Bacteria, Archaea,
and Eucaryotes 15
Some Genes Evolve Rapidly; Others Are Highly Conserved 16
Most Bacteria and Archaea Have 1000-6000 Genes 17
New Genes Are Generated from Preexisting Genes 18
Gene Duplications Give Rise to Families of Related Genes Within
a Single Cell 19
Genes Can Be Transferred Between Organisms, Both in the 21
Laboratory and in Nature
Sex Results in Horizontal Exchanges of Genetic Information
Within a Species 22
The Function of a Gene Can Often Be Deduced from Its Sequence 22
More Than 200 Gene Families Are Common to All Three Primary
Branches of the Tree of Life 23
Mutations Reveal the Functions of Genes 23
Molecular Biologists Have Focused a Spotlight on £ coli 24
Summary 26
GENETIC INFORMATION IN EUCARYOTES 26
Eucaryotic Cells May Have Originated as Predators 26
Modern Eucaryotic Cells Evolved from a Symbiosis 27
Eucaryotes Have Hybrid Genomes 30
Eucaryotic Genomes Are Big 30
Eucaryotic Genomes Are Rich in Regulatory DNA 31
The Genome Defines the Program of Multicellular Development 31
Many Eucaryotes Live as Solitary Cells: the Protists 32
A Yeast Serves as a Minimal Model Eucaryote 33
The Expression Levels of All The Genes of An Organism Can Be
Monitored Simultaneously 34
To Make Sense of Cells, We Need Mathematics, Computers, and
Quantitative Information 35
Arabidopsis Has Been Chosen Out of 300,000 Species As a Model
Plant 36
The World of Animal Cells Is Represented By a Worm, a Fly,
a Mouse, and a Human 36
Studies in Drosophila Provide a Key to Vertebrate Development 37
The Vertebrate Genome Is a Product of Repeated Duplication 38
Genetic Redundancy Is a Problem for Geneticists, But It Creates
Opportunities for Evolving Organisms 39
The Mouse Serves as a Model for Mammals 39
Humans Report on Their Own Peculiarities 40
We Are All Different in Detail 41
Summary 42
Problems 42
References 44
Chapter 2 Cell Chemistry and Biosynthesis 45
THE CHEMICAL COMPONENTS OF A CELL 45
Cells Are Made From a Few Types of Atoms 45
The Outermost Electrons Determine How Atoms Interact 46
Covalent Bonds Form by the Sharing of Electrons 48
There Are Different Types of Covalent Bonds 50
An Atom Often Behaves as if It Has a Fixed Radius 51
Water Is the Most Abundant Substance in Cells 51
Some Polar Molecules Are Acids and Bases 52
Four Types of Noncovalent Attractions Help Bring Molecules
Together in Cells 53
A Cell Is Formed from Carbon Compounds 54
Cells Contain Four Major Families of Small Organic Molecules 55
Sugars Provide an Energy Source for Cells and Are the Subunits
of Polysaccha rides 55
Fatty Acids Are Components of Cell Membranes, as Well as a
Source of Energy 58
Amino Acids Are the Subunits of Proteins 59
Nucleotides Are the Subunits of DNA and RNA 61
The Chemistry of Cells Is Dominated by Macromolecules with
Remarkable Properties 62
Noncovalent Bonds Specify Both the Precise Shape of a
Macromolecule and its Binding to Other Molecules 63
Summary 65
CATALYSIS AND THE USE OF ENERGY BY CELLS 65
Cell Metabolism Is Organized by Enzymes 66
Biological Order Is Made Possible by the Release of Heat Energy
from Cells 66
Photosynthetic Organisms Use Sunlight to Synthesize Organic
Molecules 68
Cells Obtain Energy by the Oxidation of Organic Molecules 70
Oxidation and Reduction Involve Electron Transfers 71
Enzymes Lower the Barriers That Block Chemical Reactions 72
How Enzymes Find Their Substrates: The Enormous Rapidity of
Molecular Motions 74
The Free-Energy Change for a Reaction Determines Whether It
Can Occur 75
The Concentration of Reactants Influences the Free-Energy
Change and a Reaction's Direction 76
For Sequential Reactions, A6° Values Are Additive 77
Activated Carrier Molecules Are Essential for Biosynthesis 78
The Formation of an Activated Carrier Is Coupled to an
Energetically Favorable Reaction 79
ATP Is the Most Widely Used Activated Carrier Molecule 80
Energy Stored in ATP Is Often Harnessed to Join Two Molecules
Together 81
NADH and NADPH Are Important Electron Carriers 82
There Are Many Other Activated Carrier Molecules in Cells 83
The Synthesis of Biological Polymers Is Driven by ATP Hydrolysis 84
Summary 87
HOW CELLS OBTAIN ENERGY FROM FOOD 88
Glycolysis Is a Central ATP-Producing Pathway 88
Fermentations Produce ATP in the Absence of Oxygen 89
Glycolysis Illustrates How Enzymes Couple Oxidation to Energy
Storage 91
Organisms Store Food Molecules in Special Reservoirs 91
Most Animal Cells Derive Their Energy from Fatty Acids Between
Meals 95
Sugars and Fats Are Both Degraded to Acetyl CoA in Mitochondria 96
The Citric Acid Cycle Generates NADH by Oxidizing Acetyl Groups
to CO2 97
Electron Transport Drives the Synthesis of the Majority of the ATP
in Most Cells 100
Amino Acids and Nucleotides Are Part of the Nitrogen Cycle 100
Metabolism Is Organized and Regulated 101
Summary 103
Problems 103
References 124
Chapter 3 Proteins 125
THE SHAPE AND STRUCTURE OF PROTEINS 125
The Shape of a Protein Is Specified by Its Amino Acid Sequence 125
Proteins Fold into a Conformation of Lowest Energy 130
The a Helix and the ß Sheet Are Common Folding Patterns 131
Protein Domains Are Modular Units from which Larger Proteins
Are Built 135
Few of the Many Possible Polypeptide Chains Will Be Useful
to Cells 136
Proteins Can Be Classified into Many Families 137
Sequence Searches Can Identify Close Relatives 139
Some Protein Domains Form Parts of Many Different Proteins 140
Certain Pairs of Domains Are Found Together in Many Proteins 141
The Human Genome Encodes a Complex Set of Proteins,
Revealing Much That Remains Unknown 142
Larger Protein Molecules Often Contain More Than One
Polypeptide Chain 142
Some Proteins Form Long Helical Filaments 143
Many Protein Molecules Have Elongated, Fibrous Shapes 145
Many Proteins Contain a Surprisingly Large Amount of
Unstructured Polypeptide Chain 146
Covalent Cross-Linkages Often Stabilize Extracellular Proteins 147
Protein Molecules Often Serve as Subunits for the Assembly
of Large Structures 148
Many Structures in Cells Are Capable of Self-Assembly 149
Assembly Factors Often Aid the Formation of Complex
Biological Structures 151
Summary 152
PROTEIN FUNCTION 152
All Proteins Bind to Other Molecules 153
The Surface Conformation of a Protein Determines Its Chemistry 154
Sequence Comparisons Between Protein Family Members
Highlight Crucial Ligand-Binding Sites 155
Proteins Bind to Other Proteins Through Several Types of
Interfaces 156
Antibody Binding Sites Are Especially Versatile 156
The Equilibrium Constant Measures Binding Strength 157
Enzymes Are Powerful and Highly Specific Catalysts 158
Substrate Binding Is the First Step in Enzyme Catalysis 159
Enzymes Speed Reactions by Selectively Stabilizing Transition
States 160
Enzymes Can Use Simultaneous Acid and Base Catalysis 160
Lysozyme Illustrates How an Enzyme Works 161
Tightly Bound Small Molecules Add Extra Functions to Proteins 166
MolecularTunnels Channel Substrates in Enzymes with
Multiple Catalytic Sites 167
Multienzyme Complexes Help to Increase the Rate of Cell
Metabolism 168
The Cell Regulates the Catalytic Activities of its Enzymes 169
Allosteric Enzymes Have Two or More Binding Sites That Interact 171
Two Ligands Whose Binding Sites Are Coupled Must
Reciprocally Affect Each Other's Binding 171
Symmetric Protein Assemblies Produce Cooperative Allosteric
Transitions 172
The Allosteric Transition in AspartateTranscarbamoylase Is
Understood in Atomic Detail 173
Many Changes in Proteins Are Driven by Protein
Phosphorylation 175
A Eucaryotic Cell Contains a Large Collection of Protein Kinases
and Protein Phosphatases 176
The Regulation of Cdk and Src Protein Kinases Shows How a
Protein Can Function as a Microchip 177
Proteins That Bind and Hydrolyze GTP Are Ubiquitous Cellular
Regulators 178
Regulatory Proteins Control the Activity of GTP-Binding Proteins
by Determining Whether GTP or GDP Is Bound 179
Large Protein Movements Can Be Generated From Small Ones 179
Motor Proteins Produce Large Movements in Cells 181
Membrane-Bound Transporters Harness Energy to Pump
Molecules Through Membranes 182
Proteins Often Form Large Complexes That Function as Protein
Machines 184
Protein Machines with Interchangeable Parts Make Efficient Use
of Genetic Information 184
The Activation of Protein Machines Often Involves Positioning
Them at Specific Sites 185
Many Proteins Are Controlled by Multisite Covalent Modification 186
A Complex Network of Protein Interactions Underlies Cell Function 187
Summary 190
Problems 191
References 193
Chapter 4 DNA, Chromosomes, and Genomes 195
THE STRUCTURE AND FUNCTION OF DNA 197
A DNA Molecule Consists of Two Complementary Chains
of Nucleotides 197
The Structure of DNA Provides a Mechanism for Heredity 199
In Eucaryotes, DNA Is Enclosed in a Cell Nucleus 200
Summary 201
CHROMOSOMAL DNA AND ITS PACKAGING IN THE
CHROMATIN FIBER 202
Eucaryotic DNA Is Packaged into a Set of Chromosomes 202
Chromosomes Contain Long Strings of Genes 204
The Nucleotide Sequence of the Human Genome Shows How
Our Genes Are Arranged 205
Genome Comparisons Reveal Evolutionary Conserved DNA
Sequences 207
Chromosomes Exist in Different States Throughout the Life
of a Cell 208
Each DNA Molecule That Forms a Linear Chromosome Must
Contain a Centromere, Two Telomeres, and Replication Origins 209
DNA Molecules Are Highly Condensed in Chromosomes 210
Nucleosomes Are a Basic Unit of Eucaryotic Chromosome
Structure 211
The Structure of the Nudeosome Core Particle Reveals How
DNA Is Packaged 212
Nucleosomes Have a Dynamic Structure, and Are Frequently
Subjected to Changes Catalyzed by ATP-Dependent Chromatin-
Remodeling Complexes 215
Nucleosomes Are Usually Packed Together into a Compact
Chromatin Fiber 216
Summary 218
THE REGULATION OF CHROMATIN STRUCTURE 219
Some Early Mysteries Concerning Chromatin Structure 220
Heterochromatin Is Highly Organized and Unusually Resistant
to Gene Expression 220
The Core Histones Are Covalently Modified at Many Different Sites 222
Chromatin Acquires Additional Variety through the Site-Specific
Insertion of a Small Set of Histone Variants 224
The Covalent Modifications and the Histone Variants Act in
Concert to Produce a "Histone Code"That Helps to
Determine Biological Function 224
A Complex of Code-Reader and Code-Writer Proteins Can Spread
Specific Chromatin Modifications for Long Distances Along a
Chromosome 226
Barrier DNA Sequences Block the Spread of Reader-Writer Complexes
and Thereby Separate Neighboring Chromatin Domains 227
The Chromatin in Centromeres Reveals How Histone Variants
Can Create Special Structures 228
Chromatin Structures Can Be Directly Inherited 230
Chromatin Structures Add Unique Features to Eucaryotic
Chromosome Function 231
Summary 233
DNA REPLICATION MECHANISMS
266
THE GLOBAL STRUCTURE OF CHROMOSOMES
233
234
Chromosomes Are Folded into Large Loops of Chromatin
Polytene Chromosomes Are Uniquely Useful for Visualizing
Chromatin Structures 236
There Are Multiple Forms of Heterochromatin 238
Chromatin Loops Decondense When the Genes Within Them Are
Expressed 239
Chromatin Can Move to Specific Sites Within the Nucleus to
Alter Their Gene Expression 239
Networks of Macromolecules Form a Set of Distinct Biochemical
Environments inside the Nucleus 241
Mitotic Chromosomes Are Formed from Chromatin in Its Most
Condensed State 243
Summary 245
HOW GENOMES EVOLVE
245
Genome Alterations Are Caused by Failures of the Normal
Mechanisms for Copying and Maintaining DNA 246
The Genome Sequences of Two Species Differ in Proportion to
the Length of Time That They Have Separately Evolved 247
Phylogenetic Trees Constructed from a Comparison of DNA
Sequences Trace the Relationships of All Organisms 248
A Comparison of Human and Mouse Chromosomes Shows
How the Structures of Genomes Diverge 249
The Size of a Vertebrate Genome Reflects the Relative Rates of
DNA Addition and DNA Loss in a Lineage 251
We Can Reconstruct the Sequence of Some Ancient Genomes 251
Multispecies Sequence Comparisons Identify Important DNA
Sequences of Unknown Function 252
Accelerated Changes in Previously Conserved Sequences Can
Help Decipher Critical Steps in Human Evolution 253
Gene Duplication Provides an Important Source of Genetic
Novelty During Evolution 253
Duplicated Genes Diverge 254
The Evolution of the Globin Gene Family Shows How DNA
Duplications Contribute to the Evolution of Organisms 256
Genes Encoding New Proteins Can Be Created by the
Recombination of Exons 257
Neutral Mutations Often Spread to Become Fixed in a Population,
with a Probability that Depends on Population Size 257
A Great Deal Can Be Learned from Analyses of the Variation
Among Humans 258
Summary 260
Problems 260
References 262
Chapter 5 DNA Replication, Repair, and
Recombination 263
THE MAINTENANCE OF DNA SEQUENCES 263
Mutation Rates Are Extremely Low 263
Low Mutation Rates Are Necessary for Life as We Know It 265
Summary 265
Base-Pairing Underlies DNA Replication and DNA Repair 266
The DNA Replication Fork Is Asymmetrical 266
The High Fidelity of DNA Replication Requires Several Proofreading
Mechanisms 268
Only DNA Replication in the 5'-to-3' Direction Allows Efficient Error
Correction 271
A Special Nucleotide-Polymerizing Enzyme Synthesizes Short RNA
Primer Molecules on the Lagging Strand 272
Special Proteins Help to Open Up the DNA Double Helix in Front
of the Replication Fork 273
A Sliding Ring Holds a Moving DNA Polymerase onto the DNA 273
The Proteins at a Replication Fork Cooperate to Form a Replication
Machine 275
A Strand-Directed Mismatch Repair System Removes Replication
Errors That Escape from the Replication Machine 276
DNATopoisomerases Prevent DNA Tangling During Replication 278
DNA Replication Is Fundamentally Similar in Eucaryotes and
Bacteria 280
Summary 281
THE INITIATION AND COMPLETION OF DNA REPLICATION
IN CHROMOSOMES
DNA REPAIR
HOMOLOGOUS RECOMBINATION
281
281
DNA Synthesis Begins at Replication Origins
Bacterial Chromosomes Typically Have a Single Origin of DNA
Replication 282
Eucaryotic Chromosomes Contain Multiple Origins of Replication 282
In Eucaryotes DNA Replication Takes Place During Only One Part
of the Cell Cycle 284
Different Regions on the Same Chromosome Replicate at Distinct
Times in S Phase 285
Highly Condensed Chromatin Replicates Late, While Genes in
Less Condensed Chromatin Tend to Replicate Early 285
Well-Defined DNA Sequences Serve as Replication Origins in a
Simple Eucaryote, the Budding Yeast 286
A Large Multisubunit Complex Binds to Eucaryotic Origins of
Replication 287
The Mammalian DNA Sequences That Specify the Initiation of
Replication Have Been Difficult to Identify 288
New Nudeosomes Are Assembled Behind the Replication Fork 289
The Mechanisms of Eucaryotic Chromosome Duplication Ensure
That Patterns of Histone Modification Can Be Inherited 290
Telomerase Replicates the Ends of Chromosomes 292
Telomere Length Is Regulated by Cells and Organisms 293
Summary * 294
295
Without DNA Repair, Spontaneous DNA Damage Would Rapidly
Change DNA Sequences 296
The DNA Double Helix Is Readily Repaired 296
DNA Damage Can Be Removed by More Than One Pathway 297
Coupling DNA Repair to Transcription Ensures That the Cell's Most
Important DNA Is Efficiently Repaired 299
The Chemistry of the DNA Bases Facilitates Damage Detection 300
Special DNA Polymerases Are Used in Emergencies to Repair DNA 302
Double-Strand Breaks Are Efficiently Repaired 302
DNA Damage Delays Progression of the Cell Cycle 303
Summary 304
304
Homologous Recombination Has Many Uses in the Cell 304
Homologous Recombination Has Common Features in All Cells 305
DNA Base-Pairing Guides Homologous Recombination 305
The RecA Protein and its Homologs Enable a DNA Single Strand
to Pair with a Homologous Region of DNA Double Helix 307
Branch Migration Can Either Enlarge Hetroduplex Regions or
Release Newly Synthesized DNA as a Single Strand 308
Homologous Recombination Can Flawlessly Repair Double-
Stranded Breaks in DNA 308
Cells Carefully Regulate the Use of Homologous Recombination
in DNA Repair ¦ 310
Holliday Junctions Are Often Formed During Homologous
Recombination Events 311
Meiotic Recombination Begins with a Programmed Double-
Strand Break 312
Homologous Recombination Often Results in Gene Conversion 314
Mismatch Proofreading Prevents Promiscuous Recombination
Between Two Poorly Matched DNA Sequences 315
Summary 316
TRANSPOSITION AND CONSERVATIVE SITE-SPECIFIC
RECOMBINATION 316
Through Transposition, Mobile Genetic Elements Can Insert Into
Any DNA Sequence 317
DNA-OnlyTransposons Move by Both Cut-and-Paste and Replicative
Mechanisms 317
Some Viruses Use a Transposition Mechanism to Move Themselves
into Host Cell Chromosomes 319
Retroviral-like Retrotransposons Resemble Retroviruses, but Lack a
Protein Coat 320
A Large Fraction of the Human Genome Is Composed of
Nonretroviral Retrotransposons 321
Different Transposable Elements Predominate in Different
Organisms 322
Genome Sequences Reveal the Approximate Times that
Transposable Elements Have Moved 323
Conservative Site-Specific Recombination Can Reversibly
Rearrange DNA 323
Conservative Site-Specific Recombination Was Discovered in
Bacteriophage X 324
Conservative Site-Specific Recombination Can Be Used to Turn
Genes On or Off 324
Summary 326
Problems 327
References 328
Chapter 6 How Cells Read the Genome: From
DNA to Protein 329
FROM DNA TO RNA 331
Portions of DNA Sequence Are Transcribed into RNA 332
Transcription Produces RNA Complementary to One Strand of DNA 333
Cells Produce Several Types of RNA 335
Signals Encoded in DNA Teil RNA Polymerase Where to Start and
Stop 336
Transcription Start and Stop Signals Are Heterogeneous in
Nucleotide Sequence 338
Transcription Initiation in Eucaryotes Requires Many Proteins 339
RNA Polymerase II Requires General Transcription Factors 340
Polymerase II Also Requires Activator, Mediator, and Chromatin-
Modifying Proteins 342
Transcription Elongation Produces Superhelical Tension in DNA 343
Transcription Elongation in Eucaryotes Is Tightly Coupled to RNA
Processing 345
RNA Capping Is the First Modification of Eucaryotic Pre-mRNAs 346
RNA Splicing Removes Intron Sequences from Newly Transcribed
Pre-mRNAs 347
Nucleotide Sequences Signal Where Splicing Occurs 349
RNA Splicing Is Performed by the Spliceosome 349
The Spliceosome Uses ATP Hydrolysis to Produce a Complex Series
of RNA-RNA Rearrangements 351
Other Properties of Pre-mRNA and Its Synthesis Help to Explain
the Choice of Proper Splice Sites 352
A Second Set of snRNPs Splice a Small Fraction of Intron Sequences
in Animals and Plants 353
RNA Splicing Shows Remarkable Plasticity 355
Spliceosome-Catalyzed RNA Splicing Probably Evolved from
Self-Splicing Mechanisms 355
RNA-Processing Enzymes Generate the 3' End of Eucaryotic mRNAs 357
Mature Eucaryotic mRNAs Are Selectively Exported from the
Nucleus 358
Many Noncoding RNAs Are Also Synthesized and Processed in the
Nucleus 360
The Nucleolus Is a Ribosome-Producing Factory 362
The Nucleus Contains a Variety of Subnuclear Structures 363
Summary 366
FROM RNA TO PROTEIN
366
An mRNA Sequence Is Decoded in Sets of Three Nucleotide 367
tRNA Molecules Match Amino Acids to Codons in mRNA 368
tRNAs Are Covalently Modified Before They Exit from the Nucleus 369
Specific Enzymes Couple Each Amino Acid to Its Appropriate tRNA
Molecule 370
Editing by RNA Synthetases Ensures Accuracy 371
Amino Acids Are Added to the C-terminal End of a Growing
Polypeptide Chain 373
The RNA Message Is Decoded in Ribosomes 373
Elongation Factors Drive Translation Forward and Improve Its
Accuracy 377
The Ribosome Is a Ribozyme 378
Nucleotide Sequences in mRNA Signal Where to Start Protein
Synthesis 379
Stop Codons Mark the End of Translation 381
Proteins Are Made on Polyribosomes 381
There Are Minor Variations in the Standard Genetic Code 382
Inhibitors of Procaryotic Protein Synthesis Are Useful as
Antibiotics 383
Accuracy in Translation Requires the Expenditure of Free Energy 385
Quality Control Mechanisms Act to Prevent Translation of Damaged
mRNAs 385
Some Proteins Begin to Fold While Still Being Synthesized 387
Molecular Chaperones Help Guide the Folding of Most Proteins 388
Exposed Hydrophobie Regions Provide Critical Signals for Protein
Quality Control 390
The Proteasome Is a Compartmentalized Protease with
Sequestered Active Sites 391
An Elaborate Ubiquitin-Conjugating System Marks Proteins for
Destruction 393
Many Proteins Are Controlled by Regulated Destruction 395
Abnormally Folded Proteins Can Aggregate to Cause Destructive
Human Diseases 396
There Are Many Steps From DNA to Protein 399
Summary 399
THE RNA WORLD AND THE ORIGINS OF LIFE
Life Requires Stored Information
Polynucleotides Can Both Store Information and Catalyze
Chemical Reactions
A Pre-RNA World May Predate the RNA World
Single-Stranded RNA Molecules Can Fold into Highly Elaborate
Structures
Self-Replicating Molecules Undergo Natural Selection
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
400
401
401
402
403
404
407
408
408
409
410
411
411
The Different Cell Types of a Multicellular Organism Contain the
Same DNA 411
Different Cell Types Synthesize Different Sets of Proteins 412
External Signals Can Cause a Cell to Change the Expression of
Its Genes 413
Gene Expression Can Be Regulated at Many of the Steps in the
Pathway from DNA to RNA to Protein 415
Summary 415
DNA-BINDING MOTIFS IN GENE REGULATORY PROTEINS 416
Gene Regulatory Proteins Were Discovered Using Bacterial
Genetics 416
The Outside of the DNA Helix Can Be Read by Proteins 416
Short DNA Sequences Are Fundamental Components of Genetic
Switches 418
Gene Regulatory Proteins Contain Structural Motifs That Can
Read DNA Sequences 418
The Helix-Turn-Helix Motif Is One of the Simplest and Most
Common DNA-Binding Motifs 419
Homeodomain Proteins Constitute a Special Class of Helix-Turn-
Helix Proteins 420
There Are Several Types of DNA-Binding Zinc Finger Motifs 421
ß sheets Can Also Recognize DNA 422
Some Proteins Use Loops That Enter the Major and Minor Groove
to Recognize DNA 423
The Leucine Zipper Motif Mediates Both DNA Binding and Protein
Dimerization 423
Heterodimerization Expands the Repertoire of DNA Sequences That
Gene Regulatory Proteins Can Recognize 424
The Helix-Loop-Helix Motif Also Mediates Dimerization and DNA
Binding 425
It Is Not Yet Possible to Predict the DNA Sequences Recognized
by All Gene Regulatory Proteins 426
A Gel-Mobility Shift Assay Readily Detects Sequence-Specific
DNA-Binding Proteins 427
DNA Affinity Chromatography Facilitates the Purification of
Sequence-Specific DNA-Binding Proteins 428
The DNA Sequence Recognized by a Gene Regulatory Protein
Can Be Determined Experimentally 429
Phylogenetic Footprinting Identifies DNA Regulatory Sequences
Through Comparative Genomics 431
Chromatin Immunoprecipitation Identifies Many of the Sites
That Gene Regulatory Proteins Occupy in Living Cells 431
Summary 432
HOW GENETIC SWITCHES WORK 432
TheTryptophan Repressor Is a Simple Switch That Turns Genes
On and Off in Bacteria 433
Transcriptional Activators Turn Genes On 435
ATranscriptional Activator and a Transcriptional Repressor
Control the Lac Operon 435
DNA Looping Occurs During Bacterial Gene Regulation 437
Bacteria Use Interchangeable RNA Polymerase Subunits to Help
Regulate Gene Transcription 438
Complex Switches Have Evolved to Control Gene Transcription
in Eucaryotes 439
A Eucaryotic Gene Control Region Consists of a Promoter Plus
Regulatory DNA Sequences 440
Eucaryotic Gene Activator Proteins Promote the Assembly of RNA
Polymerase and the General Transcription Factors at the
Startpoint of Transcription 441
Eucaryotic Gene Activator Proteins Also Modify Local Chromatin
Structure 442
Gene Activator Proteins Work Synergistically 444
Eucaryotic Gene Repressor Proteins Can Inhibit Transcription
in Various Ways 445
Eucaryotic Gene Regulatory Proteins Often Bind DNA
Cooperatively 445
Complex Genetic Switches That Regulate Drosophila Development
Are Built Up from Smaller Modules 447
The Drosophila Eve Gene Is Regulated by Combinatorial Controls 448
Complex Mammalian Gene Control Regions Are Also Constructed
from Simple Regulatory Modules 450
Insulators Are DNA Sequences That Prevent Eucaryotic Gene
Regulatory Proteins from Influencing Distant Genes 452
Gene Switches Rapidly Evolve 453
Summary 453
THE MOLECULAR GENETIC MECHANISMS THAT CREATE
SPECIALIZED CELL TYPES 454
DNA Rearrangements Mediate Phase Variation in Bacteria 454
A Set of Gene Regulatory Proteins Determines Cell Type in a
Budding Yeast 455
Two Proteins That Repress Each Other's Synthesis Determine the
Heritable State of Bacteriophage Lambda 457
Simple Gene Regulatory Circuits Can Be Used to Make Memory
Devices 458
Transcriptional Circuits Allow the Cell to Carry Out Logic Operations 459
Synthetic Biology Creates New Devices from Existing Biological Parts 460
Circadian Clocks Are Based on Feedback Loops in Gene Regulation 460
A Single Gene Regulatory Protein Can Coordinate the Expression
of a Set of Genes 462
Expression of a Critical Gene Regulatory Protein Can Trigger
the Expression of a Whole Battery of Downstream Genes 463
Combinatorial Gene Control Creates Many Different Cell Types
in Eucaryotes 464
A Single Gene Regulatory Protein Can Trigger the Formation
of an Entire Organ 465
The Pattern of DNA Methylation Can Be Inherited When
Vertebrate Cells Divide 467
Genomic Imprinting Is Based on DNA Methylation 468
CG-Rich Islands Are Associated with Many Genes in Mammals 470
Epigenetic Mechanisms Ensure That Stable Patterns of
Gene Expression Can Be Transmitted to Daughter Cells 471
Chromosome-Wide Alterations in Chromatin Structure
Can Be Inherited 473
The Control of Gene Expression is Intrinsically Noisy 476
Summary 477
POST-TRANSCRIPTIONAL CONTROLS 477
Transcription Attenuation Causes the Premature Termination
of Some RNA Molecules 477
Riboswitches Might Represent Ancient Forms of Gene Control 478
Alternative RNA Splicing Can Produce Different Forms of a
Protein from the Same Gene 479
The Definition of a Gene Has Had to Be Modified Since the
Discovery of Alternative RNA Splicing 480
Sex Determination in Drosophila Depends on a Regulated
Series of RNA Splicing Events 481
A Change in the Site of RNA Transcript Cleavage and Poly-A
Addition Can Change the C-terminus of a Protein 482
RNA Editing Can Change the Meaning of the RNA Message 483
RNA Transport from the Nucleus Can Be Regulated 485
Some mRNAs Are Localized to Specific Regions of the Cytoplasm 486
The 5' and 3' Untranslated Regions of mRNAs Control
Their Translation 488
The Phosphorylation of an Initiation Factor Regulates Protein
Synthesis Globally 488
Initiation at AUG Codons Upstream of the Translation Start
Can Regulate Eucaryotic Translation Initiation 489
Internal Ribosome Entry Sites Provide Opportunities for
Translation Control 491
Changes in mRNA Stability Can Regulate Gene Expression 492
Cytoplasmic Poly-A Addition Can Regulate Translation 493
Small Noncoding RNA Transcripts Regulate Many Animal and
Plant Genes 493
RNA Interference Is a Cell Defense Mechanism 495
RNA Interference Can Direct Heterochromatin Formation 496
RNA Interference Has Become a Powerful Experimental Tool 497
Summary 497
Problems 497
References 499
Chapter 8 Manipulating Proteins, DNA, and RNA 501
ISOLATING CELLS AND GROWING THEM IN CULTURE 501
Cells Can Be Isolated from Intact Tissues 502
Cells Can Be Grown in Culture 502
Eucaryotic Cell Lines Are a Widely Used Source of
Homogeneous Cells 505
Embryonic Stem Cells Could Revolutionize Medicine 505
Somatic Cell NuclearTransplantation May Provide a Way to
Generate Personalized Stem Cells 507
Hybridoma Cell Lines Are Factories That Produce Monoclonal
Antibodies 508
Summary 510
PURIFYING PROTEINS 510
Cells Can Be Separated into Their Component Fractions 510
Cell Extracts Provide Accessible Systems to Study Cell Functions 511
Proteins Can Be Separated by Chromatography 512
Affinity Chromatography Exploits Specific Binding Sites on
Proteins 513
Genetically-Engineered Tags Provide an Easy Way to Purify
Proteins 514
Purified Cell-Free Systems Are Required for the Precise Dissection of
Molecular Functions 516
Summary 516
ANALYZING PROTEINS 517
Proteins Can Be Separated by SDS Polyacrylamide-Gel
Electrophoresis 517
Specific Proteins Can Be Detected by Blotting with Antibodies 518
Mass Spectrometry Provides a Highly Sensitive Method
for Identifying Unknown Proteins 519
Two-Dimensional Separation Methods are Especially Powerful 521
Hydrodynamic Measuremerlts Reveal the Size arid Shape of
a Protein Complex 522
Sets of Interacting Proteins Can Be Identified by Biochemical
Methods 523
Protein-Protein Interactions Can Also Be Identified by a
Two-Hybrid Technique in Yeast 523
Combining Data Derived from Different Techniques Produces
Reliable Protein-Interaction Maps 524
Optical Methods Can Monitor Protein Interactions in Real Time 524
Some Techniques Can Monitor Single Molecules 526
Protein Function Can Be Selectively Disrupted with Small
Molecules 527
Protein Structure Can Be Determined Using X-Ray Diffraction 527
NMR Can Be Used to Determine Protein Structure in Solution 529
Protein Sequence and Structure Provide Clues About Protein
Function 530
Summary 531
ANALYZING AND MANIPULATING DNA 532
Restriction Nucleases Cut Large DNA Molecules into Fragments 532
Gel Electrophoresis Separates DNA Molecules of Different Sizes 534
Purified QNA Molecules Can Be Specifically Labeled with
Radioisotopes or Chemical Markers in vitro 535
Nucleic Acid Hybridization Reactions Provide a Sensitive Way of
Detecting Specific Nucleotide Sequences 535
Northern and Southern Blotting Facilitate Hybridization with
Electrophoretically Separated Nucleic Acid Molecules 538
Genes Can Be Cloned Using DNA Libraries 540
Two Types of DNA Libraries Serve'Different Purposes 541
cDNA Clones Contain Uninterrupted Coding Sequences 544
Genes Can Be Selectively Amplified by PCR 544
Cells Can Be Used As Factories to Produce Specific Proteins 546
Proteins and Nucleic Acids Can Be Synthesized Directly by
Chemical Reactions 548
DNA Can Be Rapidly Sequenced 548
Nucleotide Sequences Are Used to Predict the Amino Acid
Sequences of Proteins 550
The Genomes of Many Organisms Have Been Fully Sequenced 551
Summary 552
STUDYING GENE EXPRESSION AND FUNCTION 553
Classical Genetics Begins by Disrupting a Cell Process by Random
Mutagenesis 553
Genetic Screens Identify Mutants with Specific Abnormalities 556
Mutations Can Cause Los» or Gain of Protein Function ¦ 557
Complementation Tests Reveal Whether Two Mutations A(e
in the Same Gene or Different Genes ** 558
Genes Can Be Ordered in Pathways by Epistasis Analysis 558
Genes Identified by Mutations Can Be Cloned 559
Human Genetics Presents Special Problems and Special
Opportunities 560
Human Genes Are Inherited in Haplotype Blocks, Which Can
Aid in the Search for Mutations That Cause Disease 561
Complex Traits Are Influenced by Multiple Genes 563
Reverse Genetics Begins with a Known Gene and Determines
Which Cell Processes Require Its Function 563
Genes Can Be Re-Engineered in Several Ways 564
Engineered Genes Can Be Inserted into the Germ Line of
Many Organisms 565
Animals Can Be Genetically Altered 566
Transgenic Plants Are Important for Both Cell Biology and
Agriculture 568
Large Collections of Tagged Knockouts Provide a Tool for
Examining the Function of Every Gene in an Organism 569
RNA Interference Is a Simple and Rapid Way to Test Gene Function 571
Reporter Genes and In Situ Hybridization Reveal When and
Where a Gene Is Expressed 572
Expression of Individual Genes Can Be Measured Using
Quantitative RT-PCR 573
Microarrays Monitor the Expression of Thousands of Genes at
Once 574
Single-Cell Gene Expression Analysis Reveals Biological "Noise" 575
Summary 576
Problems 576
References 578
Chapter 9 Visualizing Cells 579
LOOKING AT CELLS IN THE LIGHT MICROSCOPE 579
The Light Microscope Can Resolve Details 0.2 u.m Apart 580
Living Cells Are Seen Clearly in a Phase-Contrast or a Differential-
Interference-Contrast Microscope 583
Images Can Be Enhanced and Analyzed by Digital Techniques 583
Intact Tissues Are Usually Fixed and Sectioned before Microscopy 585
Specific Molecules Can Be Located in Cells by Fluorescence
Microscopy 586
Antibodies Can Be Used to Detect Specific Molecules 588
Imaging of Complex Three-Dimensional Objects Is Possible
with the Optical Microscope 589
The Confocal Microscope Produces Optical Sections by Excluding
Out-of-Focus Light 590
Fluorescent Proteins Can Be Used to Tag Individual Proteins in
Living Cells and Organisms 592
Protein Dynamics Can Be Followed in Living Cells 593
Light-Emitting Indicators Can Measure Rapidly Changing
Intracellular Ion Concentrations, 596
Several Strategies Are Available by Which Membrane-lmpermeant
Substances Can Be Introduced into Cells 597
Light Can Be Used to Manipulate Microscopic Objects As Well
As to Image Them 598
Single Molecules Can Be Visualized by Using Total Internal
Reflection Fluorescence Microscopy 599
Individual Molecules Can Be Touched and Moved Using Atomic
Force Microscopy 600
Molecules Can Be Labeled with Radioisotopes 600
Radioisotopes Are Used to Trace Molecules in Cells and Organisms 602
Summary 603
LOOKING AT CELLS AND MOLECULES IN THE ELECTRON
MICROSCOPE 604
The Electron Microscope Resolves the Fine Structure of the Cell 604
Biological Specimens Require Special Preparation for the Electron
Microscope 605
Specific Macromolecules Can Be Localized by Immunogold Electron
Microscopy 606
Images of Surfaces Can Be Obtained by Scanning Electron
Microscopy 607
Metal Shadowing Allows'Surface Features to Be Examined at
High Resolution by Transmission Electron Microscopy 608
Negative Staining and Cryoelectron Microscopy Both Allow
Macromolecules to Be Viewed at High Resolution 610
Multiple Images Can Be Combined to Increase Resolution 610
Different Views of a Single Object Can Be Combined to Give a
Three-Dimensional Reconstruction 612
Summary 612
Problems 614
References 615
Chapter 10 Membrane Structure 617
THE LIPID BILAYER 617
Phosphoglycerides, Sphingolipids, and Sterols Are the Major
Lipids in Cell Membranes 618
Phospholipids Spontaneously Form Bilayers 620
The Lipid Bilayer Is a Two-Dimensional Fluid 621
The Fluidity of a Lipid Bilayer Depends on Its Composition 622
Despite Their Fluidity, Lipid Bilayers Can Form Domains of
Different Compositions 624
Lipid Droplets Are Surrounded by a Phospholipid Monolayer 625
The Asymmetry of the Lipid Bilayer Is Functionally Important 626
Glycolipids Are Found on the Surface of All Plasma Membranes 628
Summary 629
MEMBRANE PROTEINS 629
Membrane Proteins Can Be Associated with the Lipid Bilayer in
Various Ways 629
Lipid Anchors Control the Membrane Localization of Some
Signaling Proteins 630
In Most Transmembrane Proteins the Polypeptide Chain Crosses
the Lipid Bilayer in an a-Helical Conformation 631
Transmembrane a Helices Often Interact with One Another 632
Some ß Barrels Form Large Transmembrane Channels 634
Many Membrane Proteins Are Glycosylated 635
Membrane Proteins Can Be Solubilized and Purified in Detergents 636
Bacteriorhodopsin Is a Light-Driven Proton Pump That Traverses
the Lipid Bilayer as Seven a Helices 640
Membrane Proteins Often Function as Large Complexes 642
Many Membrane Proteins Diffuse in the Plane of the Membrane 642
Cells Can Confine Proteins and Lipids to Specific Domains Within
a Membrane 645
The Cortical Cytoskeleton Gives Membranes Mechanical Strength
and Restrict Membrane Protein Diffusion 646
Summary 648
Problems 648
References 650
Chapter 11 Membrane Transport of Small Molecules
and the Electrical Properties of Membranes 651
PRINCIPLES OF MEMBRANE TRANSPORT 651
Protein-Free Lipid Bilayers Are Highly Impermeable to Ions 652
There Are Two Main Classes of Membrane Transport Proteins:
Transporters and Channels 652
Active Transport Is Mediated by Transporters Coupled to an
Energy Source 653
Summary 654
TRANSPORTERS AND ACTIVE MEMBRANE TRANSPORT 654
Active Transport Can Be Driven by Ion Gradients 656
Transporters in the Plasma Membrane Regulate Cytosolic pH 657
An Asymmetric Distribution of Transporters in Epithelial Cells
Underlies the Transcellular Transport of Solutes 658
There Are Three Classes of ATP-Driven Pumps 659
The Ca2+ Pump Is the Best-Understood P-type ATPase 660
The Plasma Membrane P-type Na+-K+ Pump Establishes the
Na+ Gradient Across the Plasma Membrane 661
ABC Transporters Constitute the Largest Family of Membrane
Transport Proteins 663
Summary 667
ION CHANNELS AND THE ELECTRICAL PROPERTIES OF
MEMBRANES 667
Ion Channels Are Ion-Selective and Fluctuate Between Open and
Closed States 667
The Membrane Potential in Animal Cells Depends Mainly on K+ Leak
Channels and the K+ Gradient Across the Plasma Membrane 669
The Resting Potential Decays Only Slowly When the Na+-K+ Pump
Is Stopped 669
The Three-Dimensional Structure of a Bacterial K+ Channel Shows
How an Ion Channel Can Work 671
Aquaporins Are Permeable to Water But Impermeable to Ions 673
The Function of a Neuron Depends on Its Elongated Structure 675
Voltage-Gated Cation Channels Generate Action Potentials in
Electrically Excitable Cells 676
Myelination Increases the Speed and Efficiency of Action Potential
Propagation in Nerve Cells 678
Patch-Clamp Recording Indicates That Individual Gated Channels
Open in an AII-or-Nothing Fashion 680
Voltage-Gated Cation Channels Are Evolutionarily and Structurally
Related 682
Transmitter-Gated Ion Channels Convert Chemical Signals into
Electrical Ones at Chemical Synapses 682
Chemical Synapses Can Be Excitatory or Inhibitory 684
The Acetylcholine Receptors at the Neuromuscular Junction Are
Transmitter-Gated Cation Channels 684
Transmitter-Gated Ion Channels Are Major Targets for Psychoactive
Drugs 686
Neuromuscular Transmission Involves the Sequential Activation
of Five Different Sets of Ion Channels 687
Single Neurons Are Complex Computation Devices 688
Neuronal Computation Requires a Combination of at Least
Three Kinds of K+Channels 689
Long-Term Potentiation (LTP) in the Mammalian Hippocampus
Depends on Ca2+ Entry Through NMDA-Receptor Channels 691
Summary 692
Problems 693
References 694
Chapter 12 Intracellular Compartments and
Protein Sorting 695
THE COMPARTMENTALIZATION OF CELLS 695
All Eucaryotic Cells Have the Same Basic Set of Membrane-
Enclosed Organelles 695
Evolutionary Origins Explain theTopological Relationships of
Organelles 697
Proteins Can Move Between Compartments in Different Ways 699
Signal Sequences Direct Proteins to the Correct Cell Address 701
Most Organelles Cannot Be Constructed De Novo: They Require
Information in the Organelle Itself 702
Summary 704
THE TRANSPORT OF MOLECULES BETWEEN THE NUCLEUS
ANDTHECYTOSOL 704
Nuclear Pore Complexes Perforate the Nuclear Envelope 705
Nuclear Localization Signals Direct Nuclear Proteins to the Nucleus 705
Nuclear Import Receptors Bind to Both Nuclear Localization
Signals and NPC proteins 707
Nuclear Export Works Like Nuclear Import, But in Reverse 708
The Ran GTPase Imposes Directionality on Transport Through
NPCs 708
Transport Through NPCs Can Be Regulated by Controlling
Access to the Transport Machinery 709
During Mitosis the Nuclear Envelope Disassembles 710
Summary 712
THE TRANSPORT OF PROTEINS INTO MITOCHONDRIA
AND CHLOROPLASTS 713
Translocation into Mitochondria Depends on Signal Sequences
and Protein Translocators 713
Mitochondrial Precursor Proteins Are Imported,as Unfolded
Polypeptide Chains 715
ATP Hydrolysis and a Membrane Potential Drive Protein Import
Into the Matrix Space 716
Bacteria and Mitochondria Use Similar Mechanisms to Insert
Porins into their Outer Membrane 717
Transport Into the Inner Mitochondrial Membrane and
Intermembrane Space Occurs Via Several Routes 717
Two Signal Sequences Direct Proteins to theThylakoid
Membrane in Chloroplasts 719
Summary 720
PEROXISOMES 721
Peroxisomes Use Molecular Oxygen and Hydrogen Peroxide to
Perform Oxidative Reactions 721
A Short Signal Sequence Directs the Import of Proteins into
Peroxisomes 722
Summary 723
THE ENDOPLASMIC RETICULUM
723
724
The ER Is Structurally and Functionally Diverse
Signal Sequences Were First Discovered in Proteins Imported
into the Rough ER 726
A Signal-Recognition Particle (SRP) Directs ER Signal Sequences
to a Specific Receptor in the Rough ER Membrane 727
The Polypeptide Chain Passes Through an Aqueous Pore in the
Translocator 730
Translocation Across the ER Membrane Does Not Always Require
Ongoing Polypeptide Chain Elongation 731
In Single-Pass Transmembrane Proteins, a Single Internal ER Signal
Sequence Remains in the Lipid Bilayer as a Membrane-Spanning
a Helix 732
Combinations of Start-Transfer and Stop-Transfer Signals Determine
the Topology of Multipass Transmembrane Proteins 734
Translocated Polypeptide Chains Fold and Assemble in the Lumen
of the Rough ER 736
Most Proteins Synthesized in the Rough ER Are Glycosylated by
the Addition of a Common W-Linked Oligosaccharide 736
Oligosaccharides Are Used as Tags to Mark the State of Protein
Folding 738
Improperly Folded Proteins Are Exported from the ER and
Degraded in the Cytosol 739
Misfolded Proteins in the ER Activate an Unfolded Protein
Response 740
Some Membrane Proteins Acquire a Covalently Attached
Glycosylphosphatidylinositol (GPI) Anchor 742
The ER Assembles Most Lipid Bilayers 743
Summary 745
Problems 746
References 748
Chapter 13 Intracellular Vesicular Traffic 749
THE MOLECULAR MECHANISMS OF MEMBRANE
TRANSPORT AND THE MAINTENANCE OF
COMPARTMENTAL DIVERSITY 750
There Are Various Types of Coated Vesicles 751
The Assembly of a Clathrin Coat Drives Vesicle Formation 754
Not All Coats Form Basket-like Structures 755
Phosphoinositides Mark Organelles and Membrane Domains 757
Cytoplasmic Proteins Regulate the Pinching-Off and Uncoating
of Coated Vesicles 757
Monomeric GTPases Control Coat Assembly 758
Not All Transport Vesicles Are Spherical 760
Rab Proteins Guide Vesicle Targeting 760
SNAREs Mediate Membrane Fusion 762
Interacting SNAREs Need to Be Pried Apart Before They Can
Function Again 764
Viral Fusion Proteins and SNAREs May Use Similar Fusion
Mechanisms 764
Summary 766
TRANSPORT FROM THE ER THROUGH THE GOLGI
APPARATUS 766
Proteins Leave the ER in COPII-Coated Transport Vesicles 767
Only Proteins That Are Properly Folded and Assembled Can Leave
the ER 767
Vesicular Tubular Clusters Mediate Transport from the ER to the
Golgi Apparatus 768
The Retrieval Pathway to the ER Uses Sorting Signals 769
Many Proteins Are Selectively Retained in the Compartments in
Which They Function 771
The Golgi Apparatus Consists of an Ordered Series of
Compartments 771
Oligosaccharide Chains Are Processed in the Golgi Apparatus 773
Proteoglycans Are Assembled in the Golgi Apparatus 775
What Is the Purpose of Glycosylation? 776
Transport Through the Golgi Apparatus May Occur by Vesicular
Transport or Cisternal Maturation 777
Golgi Matrix Proteins Help Organize the Stack 778
Summary 779
TRANSPORT FROM THE TRANS GOLGI NETWORK
TO LYSOSOMES 779
Lysosomes Are the Principal Sites of Intracellular Digestion 779
Lysosomes Are Heterogeneous 780
Plant and Fungal Vacuoles Are Remarkably Versatile Lysosomes 781
Multiple Pathways Deliver Materials to Lysosomes 782
A Mannose 6-Phosphate Receptor Recognizes Lysosomal Proteins
in the Trans Golgi Network 783
The M6P Receptor Shuttles Between Specific Membranes 784
A Signal Patch in the Hydrolase Polypeptide Chain Provides
the Cue for M6P Addition 785
Defects in the GlcNAc Phosphotransferase Cause a Lysosomal
Storage Disease in Humans 785
Some Lysosomes Undergo Exocytosis 786
Summary 786
TRANSPORT INTO THE CELL FROM THE PLASMA
MEMBRANE: ENDOCYTOSIS 787
Specialized Phagocytic Cells Can Ingest Large Particles 787
Pinocytic Vesicles Form from Coated Pits in the Plasma Membrane 789
Not All Pinocytic Vesicles Are Clathrin-Coated 790
Cells Use Receptor-Mediated Endocytosis to Import Selected
Extracellular Macromolecules 791
Endocytosed Materials That Are Not Retrieved from Endosomes
End Up in Lysosomes 792
Specific Proteins Are Retrieved from Early Endosomes and
Returned to the Plasma Membrane 793
Multivesicular Bodies Form on the Pathway to Late Endosomes 795
Transcytosis Transfers Macromolecules Across Epithelial
Cell Sheets 797
Epithelial Cells Have Two Distinct Early Endosomal Compartments
but a Common Late Endosomal Compartment 798
Summary 799
TRANSPORT FROM THE TRANS GOLGI NETWORK
TO THE CELL EXTERIOR: EXOCYTOSIS 799
Many Proteins and Lipids Seem to Be Carried Automatically
from the Golgi Apparatus to the Cell Surface 800
Secretory Vesicles Bud from the Trans Golgi Network 801
Proteins Are Often Proteolytically Processed During the
Formation of Secretory Vesicles 803
Secretory Vesicles Wait Near the Plasma Membrane Until
Signaled to Release Their Contents 803
Regulated Exocytosis Can Be a Localized Response of the
Plasma Membrane and Its Underlying Cytoplasm 804
Secretory Vesicle Membrane Components Are Quickly Removed
from the Plasma Membrane 805
Some Regulated Exocytosis Events Serve to Enlarge the Plasma
Membrane 805
Polarized Cells Direct Proteins from the Trans Golgi Network to
the Appropriate Domain of the Plasma Membrane 805
Different Strategies Guide Membrane Proteins and Lipids Selectively
to the Correct Plasma Membrane Domains 806
Synaptic Vesicles Can Form Directly from Endocytic Vesicles 807
Summary 809
Problems ' 810
References 812
Chapter 14 Energy Conversion: Mitochondria
and Chloroplasts 813
THE MITOCHONDRION 815
The Mitochondrion Contains an Outer Membrane, an Inner
Membrane, and Two Internal Compartments 816
The Citric Acid Cycle Generates High-Energy Electrons 817
A Chemiosmotic Process Converts Oxidation Energy into ATP 817
NADH Transfers its Electrons to Oxygen Through Three Large
Respiratory Enzyme Complexes 819
As Electrons Move Along the Respiratory Chain, Energy Is Stored
as an Electrochemical Proton Gradient Across the Inner
Membrane 820
The Proton Gradient Drives ATP Synthesis 821
The Proton Gradient Drives Coupled Transport Across the Inner
Membrane 822
Proton Gradients Produce Most of the Cell's ATP 822
Mitochondria Maintain a High ATP:ADP Ratio in Cells 823
A Large Negative Value of AG for ATP Hydrolysis Makes ATP
Useful to the Cell 824
ATP Synthase Can Function in Reverse to Hydrolyze ATP and
Pump H+ 826
Summary 827
ELECTRON-TRANSPORT CHAINS AND THEIR PROTON
PUMPS 827
Protons Are Unusually Easy to Move 827
The Redox Potential Is a Measure of Electron Affinities 828
Electron Transfers Release Large Amounts of Energy 829
Spectroscopic Methods Identified Many Electron Carriers in the
Respiratory Chain 829
The Respiratory Chain Includes Three Large Enzyme Complexes
Embedded in the Inner Membrane 831
An Iron-Copper Center in Cytochrome Oxidase Catalyzes Efficient
O2 Reduction 832
Electron Transfers in the Inner Mitochondrial Membrane Are Mediated
by Electron Tunneling during Random Collisions 834
A Large Drop in Redox Potential Across Each of the Three Respiratory
Enzyme Complexes Provides the Energy for H+ Pumping 835
The H+ Pumping Occurs by Distinct Mechanisms in theThree Major
Enzyme Complexes 835
H+ lonophores Uncouple Electron Transport from ATP Synthesis 836
Respiratory Control Normally Restrains Electron Flow Through
the Chain 837
Natural Uncouplers Convert the Mitochondria in Brown Fat into
Heat-Generating Machines 838
The Mitochondrion Plays Many Critical Roles in Cell Metabolism 838
Bacteria Also Exploit Chemiosmotic Mechanisms to Harness
Energy 839
Summary 840
CHLOROPLASTS AND PHOTOSYNTHESIS
840
The Chloroplast Is One Member of the Plastid Family of
Organelles 841
Chloroplasts Resemble Mitochondria But Have an Extra
Compartment 842
Chloroplasts Capture Energy from Sunlight and Use It to Fix
Carbon 843
Carbon Fixation Is Catalyzed by Ribulose Bisphosphate
Carboxylase 844
Each CO2 Molecule That Is Fixed Consumes Three Molecules
of ATP and Two Molecules of NADPH 845
Carbon Fixation in Some Plants Is Compartmentalized to Facilitate
Growth at Low CO2 Concentrations 846
Photosynthesis Depends on the Photochemistry of Chlorophyll
Molecules 847
A Photochemical Reaction Center Plus an Antenna Complex
Form a Photosystem 848
In a Reaction Center, Light Energy Captured by Chlorophyll
Creates a Sfrong Electron-Donor from a Weak One 849
Noncyclic Photophosphorylation Produces Both NADPH and ATP 850
Chloroplasts Can Make ATP by Cyclic Photophosphorylation
Without Making NADPH 853
Photosystems I and II Have Related Structures, and Also Resemble
Bacterial Photosystems 853
The Proton-Motive Force Is the Same in Mitochondria and
Chloroplasts 853
Carrier Proteins in the Chloroplast Inner Membrane Control
Metabolite Exchange with the Cytosol 854
Chloroplasts Also Perform Other Crucial Biosyntheses 855
Summary 855
THE GENETIC SYSTEMS OF MITOCHONDRIA AND
PLASTIDS
855
Mitochondria and Chloroplasts Have Diverse Genomes 859
Mitochondria and Chloroplasts Probably Both Evolved from
Endosymbiotic Bacteria 859
Mitochondria Have a Relaxed Codon Usage and Can Have a
Variant Genetic Code 861
Animal Mitochondria Contain the Simplest Genetic Systems Known 862
Some Organelle Genes Contain Introns 863
The Chloroplast Genome of Higher Plants Contains About
120 Genes 863
Mitochondrial Genes Are Inherited by a Non-Mendelian
Mechanism 864
Organelle Genes Are Maternally Inherited in Many Organisms 866
Petite Mutants in Yeasts Demonstrate the Overwhelming
Importance of the Cell Nucleus for Mitochondrial Biogenesis 866
Mitochondria and Plastids Contain Tissue-Specific Proteins that
Are Encoded in the Cell Nucleus 867
Mitochondria Import Most of Their Lipids; Chloroplasts Make
Most of Theirs 867
Mitochondria May Contribute to the Aging of Cells and Organisms 868
Why Do Mitochondria and Chloroplasts Have Their Own Genetic
Systems? 868
Summary 870
THE EVOLUTION OF ELECTRON-TRANSPORT CHAINS 870
The Earliest Cells Probably Used Fermentation to Produce ATP 870
Electron-Transport Chains Enabled Anaerobic Bacteria to Use
Nonfermentable Molecules as Their Major Source of Energy 871
By Providing an Inexhaustible Source of Reducing Power,
Photosynthetic Bacteria Overcame a Major Evolutionary
Obstacle 872
The Photosynthetic Electron-Transport Chains of Cyanobacteria
Produced Atmospheric Oxygen and Permitted New Life-Forms 873
Summary 875
Problems ' 877
References 878
Chapter 15 Mechanisms of Cell Communication 879
GENERAL PRINCIPLES OF CELL COMMUNICATION
879
880
Mitochondria and Chloroplasts Contain Complete Genetic Systems 856
Organelle Growth and Division Determine the Number of
Mitochondria and Plastids in a Cell 857
Extracellular Signal Molecules Bind to Specific Receptors
Extracellular Signal Molecules Can Act Over Either Short or Long
Distances 881
Gap Junctions Allow Neighboring Cells to Share Signaling
Information 884
Each Cell Is Programmed to Respond to Specific Combinations of
Extracellular Signal Molecules 884
Different Types of Cells Usually Respond Differently to the Same
Extracellular Signal Molecule 885
The Fate of Some Developing Cells Depends on Their Position in
Morphogen Gradients 886
A Cell Can Alter the Concentration of an Intracellular Molecule
Quickly Only If the Lifetime of the Molecule Is Short 886
Nitric Oxide Gas Signals by Directly Regulating the Activity of
Specific Proteins Inside the Target Cell 887
Nuclear Receptors Are Ligand-Modulated Gene Regulatory
Proteins . 889
TheThree Largest Classes of Cell-Surface Receptor Proteins Are lon-
Channel-Coupled, G-Protein-Coupled, and Enzyme-Coupled
Receptors 891
Most Activated Cell-Surface Receptors Relay Signals Via Small
Molecules and a Network of Intracellular Signaling Proteins 893
Many Intracellular Signaling Proteins Function as Molecular Switches
That Are Activated by Phosphorylation or GTP Binding 895
Intracellular Signaling Complexes Enhance the Speed, Efficiency,
and Specificity of the Response 897
Modular Interaction Domains Mediate Interactions Between
Intracellular Signaling Proteins 897
Cells Can Use Multiple Mechanisms to Respond Abruptly to
a Gradually Increasing Concentration of an Extracellular Signal 899
Intracellular Signaling Networks Usually Make Use of
Feedback Loops 901
Cells Can Adjust Their Sensitivity to a Signal 902
Summary 903
SIGNALING THROUGH G-PROTEIN-COUPLED CELL-
SURFACE RECEPTORS (GPCRS) AND SMALL
INTRACELLULAR MEDIATORS
904
Trimeric G Proteins Relay Signals from GPCRs 905
Some G Proteins Regulate the Production of Cyclic AMP 905
Cyclic-AMP-Dependent Protein Kinase (PKA) Mediates Most
of the Effects of Cyclic AMP 908
Some G Proteins Activate An Inositol Phospholipid Signaling
Pathway by Activating Phospholipase C-ß 909
Ca2+ Functions as a Ubiquitous Intracellular Mediator 912
The Frequency of Ca2+ Oscillations Influences a Cell's Response 912
Ca2+/Calmodulin-Dependent Protein Kinases (CaM-Kinases)
Mediate Many of the Responses to Ca2+ Signals in Animal Cells 914
Some G Proteins Directly Regulate Ion Channels 916
Smell and Vision Depend on GPCRs That Regulate Cyclic-
Nucleotide-Gated Ion Channels 917
Intracellular Mediators and Enzymatic Cascades Amplify
Extracellular Signals 919
GPCR Desensitization Depends on Receptor Phosphorylation 920
Summary 921
SIGNALING THROUGH ENZYME-COUPLED CELL-SURFACE
RECEPTORS
921
Activated Receptor Tyrosine Kinases (RTKs) Phosphorylate
Themselves 922
Phosphorylated Tyrosines on RTKs Serve as Docking Sites for
Intracellular Signaling Proteins 923
Proteins with SH2 Domains Bind to Phosphorylated Tyrosines 924
Ras Belongs to a Large Superfamily of Monomeric GTPases 926
RTKs Activate Ras Via Adaptors and GEFs: Evidence from the
Developing Drosophila Eye 927
Ras Activates a MAP Kinase Signaling Module 928
Scaffold Proteins Help Prevent Cross-Talk Between Parallel MAP
Kinase Modules 930
Rho Family GTPases Functionally Couple Cell-Surface Receptors
to the Cytoskeleton 931
PI 3-Kinase Produces Lipid Docking Sites in the Plasma Membrane 932
The PI-3-Kinase-Akt Signaling Pathway Stimulates Animal Cells to
Survive and Grow 934
The Downstream Signaling Pathways Activated By RTKs and GPCRs
Overlap 935
Tyrosine-Kinase-Associated Receptors Depend on Cytoplasmic
Tyrosine Kinases 935
Cytokine Receptors Activate the JAK-STAT Signaling Pathway,
Providing a Fast Track to the Nucleus 937
Protein Tyrosine Phosphatases Reverse Tyrosine Phosphorylations 938
Signal Proteins of theTGFß Superfamily Act Through Receptor
Serine/Threonine Kinases and Smads 939
Serine/Threonine and Tyrosine Protein Kinases Are Structurally
Related 941
Bacterial Chemotaxis Depends on a Two-Component Signaling
Pathway Activated by Histidine-Kinase-Associated Receptors 941
Receptor Methylation Is Responsible for Adaptation in Bacterial
Chemotaxis 943
Summary 944
SIGNALING PATHWAYS DEPENDENT ON REGULATED
PROTEOLYSIS OF LATENT GENE REGULATORY PROTEINS
The Receptor Protein Notch Is a Latent Gene Regulatory Protein
Wnt Proteins Bind to Frizzled Receptors and Inhibit the
Degradation of ß-Catenin
Hedgehog Proteins Bind to Patched Relieving Its Inhibition
of Smoothened
Many Stressful and Inflammatory Stimuli Act Through an
NFKB-Dependent Signaling Pathway
Summary
946
946
948
950
952
954
955
SIGNALING IN PLANTS
Multicellularity and Cell Communication Evolved Independently
in Plants and Animals 955
Receptor Serine/Threonine Kinases Are the Largest Class of
Cell-Surface Receptors in Plants 956
Ethylene Blocks the Degradation of Specific Gene Regulatory
Proteins in the Nucleus 957
Regulated Positioning of Auxin Transporters Patterns Plant Growth 959
Phytochromes Detect Red Light, and Cryptochromes Detect Blue
Light 960
Summary 961
Problems 962
References 964
Chapter 16 The Cytoskeleton 965
THE SELF-ASSEMBLY AND DYNAMIC STRUCTURE OF
CYTOSKELETAL FILAMENTS 965
Cytoskeletal Filaments Are Dynamic and Adaptable 966
The Cytoskeleton Can Also Form Stable Structures 969
Each Type of Cytoskeletal Filament Is Constructed from Smaller
Protein Subunits 970
Filaments Formed from Multiple Protofilaments Have
Advantageous Properties 971
Nucleation Is the Rate-Limiting Step in the Formation of
a Cytoskeletal Polymer 973
The Tubulin and Actin Subunits Assemble Head-to-Tail to
Create Polar Filaments 973
Microtubules and Actin Filaments Have Two Distinct Ends
That Grow at Different Rates 975
Filament Treadmilling and Dynamic Instability Are Consequences
of Nucleotide Hydrolysis by Tubulin and Actin 976
Treadmilling and Dynamic Instability Aid Rapid Cytoskeletal
Rearrangement 980
Tubulin and Actin Have Been Highly Conserved During
Eucaryotic Evolution 982
Intermediate Filament Structure Depends on The Lateral
Bundling and Twisting of Coiled Coils 983
Intermediate Filaments Impart Mechanical Stability to
Animal Cells 985
Drugs Can Alter Filament Polymerization 987
Bacterial Cell Organization and Cell Division Depend on
Homologs of the Eucaryotic Cytoskeleton 989
Summary 991
HOW CELLS REGULATE THEIR CYTOSKELETAL FILAMENTS 992
A Protein Complex Containing y-Tubulin Nucleates Microtubules 992
Microtubules Emanate from the Centrosome in Animal Cells 992
Actin Filaments Are Often Nucleated at the Plasma Membrane 996
The Mechanism of Nucleation Influences Large-Scale Filament
Organization 998
Proteins That Bind to the Free Subunits Modify Filament Elongation 999
Severing Proteins Regulate the Length and Kinetic Behavior of
Actin Filaments and Microtubules 1000
Proteins That Bind Along the Sides of Filaments Can Either Stabilize
or Destabilize Them 1001
Proteins That Interact with Filament Ends Can Dramatically Change
Filament Dynamics 1002
Different Kinds of Proteins Alter the Properties of Rapidly Growing
Microtubule Ends 1003
Filaments Are Organized into Higher-Order Structures in Cells 1005
Intermediate Filaments Are Cross-Linked and Bundled Into
Strong Arrays 1005
Cross-Linking Proteins with Distinct Properties Organize Different
Assemblies of Actin Filaments 1006
Filamin and Spectrin Form Actin Filament Webs 1008
Cytoskeletal Elements Make Many Attachments to Membrane 1009
Summary 1010
MOLECULAR MOTORS 1010
Actin-Based Motor Proteins Are Members of the Myosin
Superfamily 1011
There Are Two Types of Microtubule Motor Proteins: Kinesins and
Dyneins 1014
The Structural Similarity of Myosin and Kinesin Indicates a
Common Evolutionary Origin 1015
Motor Proteins Generate Force by Coupling ATP Hydrolysis to
Conformational Changes 1016
Motor Protein Kinetics Are Adapted to Cell Functions 1020
Motor Proteins Mediate the IntracellularTransport of Membrane-
Enclosed Organelles 1021
The Cytoskeleton Localizes Specific RNA Molecules 1022
Cells Regulate Motor Protein Function 1023
Summary 1025
THE CYTOSKELETON AND CELL BEHAVIOR
1025
Sliding of Myosin II and Actin Filaments Causes Muscles to
Contract 1026
A Sudden Rise in Cytosolic Ca2+Concentration Initiates Muscle
Contraction 1028
Heart Muscle Is a Precisely Engineered Machine 1031
Cilia and Flagella Are Motile Structures Built from Microtubules
and Dyneins 1031
Construction of the Mitotic Spindle Requires Microtubule
Dynamics and the Interactions of Many Motor Proteins 1034
Many Cells Can Crawl Across A Solid Substratum 1036
Actin Polymerization Drives Plasma Membrane Protrusion 1037
Cell Adhesion and Traction Allow Cells to Pull Themselves
Forward 1040
Members of the Rho Protein Family Cause Major Rearrangements
of the Actin Cytoskeleton 1041
Extracellular Signals Can Activate the Three Rho Protein
Family Members 1043
External Signals Can Dictate the Direction of Cell Migration 1045
Communication Between the Microtubule and Actin Cytoskeletons
Coordinates Whole-Cell Polarization and Locomotion 1046
The Complex Morphological Specialization of Neurons Depends
on the Cytoskeleton 1047
Summary 1050
Problems 1050
References 1052
Chapter 17 The Cell Cycle 1053
OVERVIEW OF THE CELL CYCLE 1054
The Eucaryotic Cell Cycle Is Divided into Four Phases 1054
Cell-Cycle Control Is Similar in All Eucaryotes 1056
Cell-Cycle Control Can Be Dissected Genetically by Analysis of
Yeast Mutants 1056
Cell-Cycle Control Can Be Analyzed Biochemically in Animal
Embryos 1057
Cell-Cycle Control Can Be Studied in Cultured Mammalian Cells 1059
Cell-Cycle Progression Can Be Studied in Various Ways 1059
Summary 1060
THE CELL-CYCLE CONTROL SYSTEM 1060
The Cell-Cycle Control System Triggers the Major Events of the
Cell Cycle 1060
The Cell-Cycle Control System Depends on Cyclically Activated
Cyclin-Dependent Protein Kinases (Cdks) 1062
Inhibitory Phosphorylation and Cdk Inhibitory Proteins (CKIs)
Can Suppress Cdk Activity 1063
The Cell-Cycle Control System Depends on Cyclical Proteolysis 1064
Cell-Cycle Control Also Depends on Transcriptional Regulation 1065
The Cell-Cycle Control System Functions as a Network of
Biochemical Switches 1065
Summary 1067
SPHASE 1067
S-Cdk Initiates DNA Replication Once Per Cycle 1067
Chromosome Duplication Requires Duplication of Chromatin
Structure 1069
Cohesins Help Hold Sister Chromatids Together 1070
Summary 1071
MITOSIS 1071
M-Cdk Drives Entry Into Mitosis 1071
Dephosphorylation Activates M-Cdk at the Onset of Mitosis 1074
Condensin Helps Configure Duplicated Chromosomes for
Separation 1075
The Mitotic Spindle Is a Microtubule-Based Machine 1075
Microtubule-Dependent Motor Proteins Govern Spindle
Assembly and Function 1077
Two Mechanisms Collaborate in the Assembly of a Bipolar Mitotic
Spindle 1077
Centrosome Duplication Occurs Early in the Cell Cycle 1078
M-Cdk Initiates Spindle Assembly in Prophase 1078
The Completion of Spindle Assembly in Animal Cells Requires
Nuclear Envelope Breakdown 1079
Microtubule Instability Increases Greatly in Mitosis 1080
Mitotic Chromosomes Promote Bipolar Spindle Assembly 1081
Kinetochores Attach Sister Chromatids to the Spindle 1082
Bi-Orientation Is Achieved by Trial and Error 1083
Multiple Forces Move Chromosomes on the Spindle 1085
The APC/C Triggers Sister-Chromatid Separation and the
Completion of Mitosis 1087
Unattached Chromosomes Block Sister-Chromatid Separation:
The Spindle Assembly Checkpoint 1088
Chromosomes Segregate in Anaphase A and B 1089
Segregated Chromosomes Are Packaged in Daughter Nuclei at
Telophase 1090
Meiosis Is a Special Form of Nuclear Division Involved in Sexual
Reproduction 1090
Summary 1092
CYTOKINESIS 1092
Actin and Myosin II in the Contractile Ring Generate the Force for
Cytokinesis 1093
Local Activation of RhoA Triggers Assembly and Contraction of the
Contractile Ring 1094
The Microtubules of the Mitotic Spindle Determine the Plane of
Animal Cell Division 1095
The Phragmoplast Guides Cytokinesis in Higher Plants 1097
Membrane-Enclosed Organelles Must Be Distributed to Daughter
Cells During Cytokinesis 1098
Some Cells Reposition Their Spindle to Divide Asymmetrically 1099
Mitosis Can Occur Without Cytokinesis 1099
The Gi Phase Is a Stable State of Cdk Inactivity 1100
Summary 1101
CONTROL OF CELL DIVISION AND CELL GROWTH
Mitogens Stimulate Cell Division
Cells Can Delay Division by Entering a Specialized Nondividing
State
Mitogens Stimulate GrCdk and Gj/S-Cdk Activities
DNA Damage Blocks Cell Division: The DNA Damage Response
Many Human Cells Have a Built-in Limitation on the Number
of Times They Can Divide
Abnormal Proliferation Signals Cause Cell-Cycle Arrest or
Apoptosis, Except in Cancer Cells
Organism and Organ Growth Depend on Cell Growth
Proliferating Cells Usually Coordinate Their Growth and Division
Neighboring Cells Compete for Extracellular Signal Proteins
Animals Control Total Cell Mass by Unknown Mechanisms
Summary
Problems
References
Chapter 18 Apoptosis
Programmed Cell Death Eliminates Unwanted Cells
Apoptotic Cells Are Biochemically Recognizable
Apoptosis Depends on an Intracellular Proteolytic Cascade
That Is Mediated by Caspases
Cell-Surface Death Receptors Activate the Extrinsic Pathway
of Apoptosis
The Intrinsic Pathway of Apoptosis Depends on Mitochondria
Bcl2 Proteins Regulate the Intrinsic Pathway of Apoptosis
lAPs Inhibit Caspases
Extracellular Survival Factors Inhibit Apoptosis in Various Ways
1101
1102
1103
1103
1105
1007
1107
1108
1108
1110
1111
1112
1112
1113
1115
1115
1117
1118
1120
1121
1121
1124
1126
Either Excessive or Insufficient Apoptosis Can Contribute to Disease 1127
Summary 1128
Problems 1128
References 1129
Chapter 19 Cell Junctions, Cell Adhesion, and
the Extracellular Matrix 1131
CADHERINS AND CELL-CELL ADHESION 1133
Cadherins Mediate Ca2+-Dependent Cell-Cell Adhesion in
All Animals 1135
The Cadherin Superfamily in Vertebrates Includes Hundreds of
Different Proteins, Including Many with Signaling
Functions 1136
Cadherins Mediate Homophilic Adhesion 1137
Selective Cell-Cell Adhesion Enables Dissociated Vertebrate
Cells to Reassemble into Organized Tissues 1139
Cadherins Control the Selective Assortment of Cells 1140
Twist Regulates Epithelial-Mesenchymal Transitions 1141
Catenins Link Classical Cadherins to the Actin Cytoskeleton 1142
Adherens Junctions Coordinate the Actin-Based Motility of
Adjacent Cells 1142
Desmosome Junctions Give Epithelia Mechanical Strength 1143
Cell-Cell Junctions Send Signals into the Cell Interior 1145
Selectins Mediate Transient Cell-Cell Adhesions in the
Bloodstream 1145
Members of the Immunoglobulin Superfamily of Proteins
Mediate Ca2+-lndependent Cell-Cell Adhesion 1146
Many Types of Cell Adhesion Molecules Act in Parallel to Create
a Synapse 1147
Scaffold Proteins Organize Junctional Complexes 1148
Summary 1149
TIGHT JUNCTIONS AND THE ORGANIZATION OF
EPITHELIA 1150
Tight Junctions Form a Seal Between Cells and a Fence Between
Membrane Domains 1150
Scaffold Proteins in Junctional Complexes Play a Key Part in
the Control of Cell Proliferation 1153
Cell-Cell Junctions and the Basal Lamina Govern Apico-Basal
Polarity in Epithelia 1155
A Separate Signaling System Controls Planar Cell Polarity 1157
Summary ' 1158
PASSAGEWAYS FROM CELL TO CELL: GAP JUNCTIONS
AND PLASMODESMATA 1158
Gap Junctions Couple Cells Both Electrically and Metabolically 1158
A Gap-Junction Connexon Is Made Up of Six Transmembrane
Connexin Subunits 1159
Gap Junctions Have Diverse Functions ' 1161
Cells Can Regulate the Permeability of Their Gap Junctions 1161
In Plants, Plasmodesmata Perform Many of the Same Functions
as Gap Junctions 1162
Summary 1163
THE BASAL LAMINA 1164
Basal Laminae Underlie All Epithelia and Surround Some
Nonepithelial Cell Types 1164
Laminin Is a Primary Component of the Basal Lamina 1165
Type IV Collagen Gives the Basal Lamina Tensile Strength 1166
Basal Laminae Have Diverse Functions 1167
Summary 1169
INTEGRINS AND CELL-MATRIX ADHESION 1169
Integrins Are Transmembrane HeterodimersThat Link to the
Cytoskeleton 1170
Integrins Can Switch Between an Active and an Inactive
Conformation 1170
Integrin Defects Are Responsible for Many Different Genetic
Diseases 1172
Integrins Cluster to Form Strong Adhesions 1174
Extracellular Matrix Attachments Act Through Integrins to
Control Cell Proliferation and Survival 1175
Integrins Recruit Intracellular Signaling Proteins at Sites of Cell-
Substratum Adhesion 1176
Integrins Can Produce Localized Intracellular Effects 1177
Summary 1178
THE EXTRACELLULAR MATRIX OF ANIMAL CONNECTIVE
TISSUES
1178
The Extracellular Matrix Is Made and Oriented by the Cells
Within It 1179
Glycosaminoglycan (GAG) Chains Occupy Large Amounts of
Space and Form Hydrated Gels 1179
Hyaluronan Acts as a Space Filler and a Facilitator of Cell Migration
During Tissue Morphogenesis and Repair 1180
Proteoglycans Are Composed of GAG Chains Covalently Linked
to a Core Protein 1181
Proteoglycans Can Regulate the Activities of Secreted Proteins 1182
Cell-Surface Proteoglycans Act as Co-Receptors 1183
Collagens Are the Major Proteins of the Extracellular Matrix 1184
Collagen Chains Undergo a Series of Post-Translational
Modifications 1186
Propeptides Are Clipped Off Procollagen After Its Secretion
to Allow Assembly of Fibrils 1187
Secreted Fibril-Associated Collagens Help Organize the Fibrils 1187
Cells Help Organize the Collagen Fibrils They Secrete by
Exerting Tension on the Matrix 1189
Elastin Gives Tissues Their Elasticity 1189
Fibronectin Is an Extracellular Protein That Helps Cells Attach
to the Matrix 1191
Tension Exerted by Cells Regulates Assembly of Fibronectin
Fibrils 1191
Fibronectin Binds to Integrins Through an RGD Motif 1193
Cells Have to Be Able to Degrade Matrix, as Well as Make it 1193
Matrix Degradation Is Localized to the Vicinity of Cells 1194
Summary 1195
THE PLANT CELL WALL 1195
The Composition of the Cell Wall Depends on the Cell Type 1195
The Tensile Strength of the Cell Wall Allows Plant Cells to
Develop Turgor Pressure 1197
The Primary Cell Wall Is Built from Cellulose Microfibrils
Interwoven with a Network of Pectic Polysaccharides 1197
Oriented Cell-Wall Deposition Controls Plant Cell Growth 1199
Microtubules Orient Cell-Wall Deposition 1200
Summary 1202
Problems 1202
References 1204
Chapter 20 Cancer 1205
CANCER AS A MICROEVOLUTIONARY PROCESS 1205
Cancer Cells Reproduce Without Restraint and Colonize
Other Tissues 1206
Most Cancers Derive from a Single Abnormal Cell 1207
Cancer Cells Contain Somatic Mutations 1208
A Single Mutation Is Not Enough to Cause Cancer 1209
Cancers Develop Gradually from Increasingly Aberrant Cells 1210
Cervical Cancers Are Prevented by Early Detection 1211
Tumor Progression Involves Successive Rounds of Random
Inherited Change Followed by Natural Selection 1212
The Epigenetic Changes That Accumulate in Cancer Cells Involve
Inherited Chromatin Structures and DNA Methylation 1213
Human Cancer Cells Are Genetically Unstable 1214
Cancerous Growth Often Depends on Defective Control of
Cell Death, Cell Differentiation, or Both 1215
Cancer Cells Are Usually Altered in Their Responses to DNA
Damage and Other Forms of Stress 1216
Human Cancer Cells Escape a Built-in Limit to Cell Proliferation 1217
A Small Population of Cancer Stem Cells Maintains Many
Tumors 1217
How Do Cancer Stem Cells Arise? 1218
To Metastasize, Malignant Cancer Cells Must Survive and
Proliferate in a Foreign Environment 1220
Tumors Induce Angiogenesis 1220
The Tumor Microenvironment Influences Cancer
Development 1222
Many Properties Typically Contribute to Cancerous Growth 1223
Summary 1223
THE PREVENTABLE CAUSES OF CANCER 1224
Many, But Not All, Cancer-Causing Agents Damage DNA 1225
Tumor Initiators Damage DNA;Tumor Promoters Do Not 1226
Viruses and Other Infections Contribute to a Significant
Proportion of Human Cancers 1227
Identification of Carcinogens Reveals Ways to Avoid
Cancer 1229
Summary 1230
FINDING THE CANCER-CRITICAL GENES 1230
The Identification of Gain-of-Function and Loss-of-Function
Mutations Requires Different Methods 1231
Retroviruses Can Act as Vectors for Oncogenes That Alter
Cell Behavior 1232
Different Searches for Oncogenes Have Converged on the
Same Gene—Ras 1233
Studies of Rare Hereditary Cancer Syndromes First Identified
Tumor Suppressor Genes 1234
Tumor Suppressor Genes Can Also Be Identified from Studies
of Tumors 1235
Both Genetic and Epigenetic Mechanisms Can Inactivate Tumor
Suppressor Genes 1235
Genes Mutated in Cancer Can Be Made Overactive in Many
Ways 1237
The Hunt for Cancer-Critical Genes Continues 1239
Summary 1240
THE MOLECULAR BASIS OF CANCER-CELL BEHAVIOR 1240
Studies of Both Developing Embryos and Genetically
Engineered Mice Have Helped to Uncover the Function of
Cancer-Critical Genes 1241
Many Cancer-Critical Genes Regulate Cell Proliferation 1242
Distinct Pathways May Mediate the Disregulation of Cell-Cycle
Progression and the Disregulation of Cell Growth in
Cancer Cells 1244
Mutations in Genes That Regulate Apoptosis Allow Cancer Cells
to Survive When They Should Not 1245
Mutations in the p53 Gene Allow Many Cancer Cells to Survive
and Proliferate Despite DNA Damage 1246
DNA Tumor Viruses Block the Action of Key Tumor Suppressor
Proteins 1247
The Changes in Tumor Cells That Lead to Metastasis Are Still
Largely a Mystery 1249
Colorectal Cancers Evolve Slowly Via a Succession of Visible
Changes 1250
A Few Key Genetic Lesions Are Common to a Large Fraction of
Colorectal Cancers 1251
Some Colorectal Cancers Have Defects in DNA Mismatch Repair 1254
The Steps of Tumor Progression Can Often Be Correlated with
Specific Mutations 1254
Each Case of Cancer Is Characterized by Its Own Array of Genetic
Lesions 1256
Summary 1256
CANCER TREATMENT: PRESENT AND FUTURE 1256
The Search for Cancer Cures Is Difficult but Not Hopeless 1257
Traditional Therapies Exploit the Genetic Instability and Loss of
Cell-Cycle Checkpoint Responses in Cancer Cells 1257
New Drugs Can Exploit the Specific Cause of a Tumor's Genetic
Instability 1257
Genetic Instability Helps Cancers Become Progressively More
Resistant to Therapies 1259
New Therapies Are Emerging from Our Knowledge of Cancer
Biology 1260
Small Molecules Can Be Designed to Inhibit Specific Oncogenic
Proteins 1260
Tumor Bloodvessels Are Logical Targets for Cancer Therapy 1262
Many Cancers May Be Treatable by Enhancing the Immune
Response Against a Specific Tumor 1262
Treating Patients with Several Drugs Simultaneously Has
Potential Advantages for Cancer Therapy 1263
Gene Expression Profiling Can Help Classify Cancers into
Clinically Meaningful Subgroups 1264
There Is Still Much More to Do 1264
Summary 1265
Problems 1265
References 1267
Chapter 21 Sexual Reproduction: Meiosis,
Germ Cells, and Fertilization 1269
OVERVIEW OF SEXUAL REPRODUCTION 1269
The Haploid Phase in Higher Eucaryotes Is Brief 1269
Meiosis Creates Genetic Diversity 1271
Sexual Reproduction Gives Organisms a Competitive Advantage 1271
Summary 1272
MEIOSIS
1272
1272
Gametes Are Produced by Two Meiotic Cell Divisions
Duplicated Homologs (and Sex Chromosomes) Pair During Early
Prophase I 1274
Homolog Pairing Culminates in the Formation of a Synaptonemal
Complex 1275
Homolog Segregation Depends on Meiosis-Specific, Kinetochore-
Associated Proteins 1276
Meiosis Frequently Goes Wrong 1278
Crossing-Over Enhances Genetic Reassortment 1279
Crossing-Over Is Highly Regulated 1280
Meiosis Is Regulated Differently in Male and Female Mammals 1280
Summary 1281
PRIMORDIAL GERM CELLS AND SEX DETERMINATION IN
MAMMALS 1282
Signals from Neighbors Specify PGCs in Mammalian Embryos 1282
PGCs Migrate into the Developing Gonads 1283
The Sry Gene Directs the Developing Mammalian Gonad to
Become a Testis 1283
Many Aspects of Sexual Reproduction Vary Greatly between
Animal Species 1285
Summary 1286
EGGS 1287
An Egg Is Highly Specialized for Independent Development 1287
Eggs Develop in Stages 1288
Oocytes Use Special Mechanisms to Grow to Their Large Size 1290
Most Human Oocytes Die Without Maturing 1291
Summary 1292
SPERM 1292
Sperm Are Highly Adapted for Delivering Their DNA to an Egg 1292
Sperm Are Produced Continuously in the Mammalian Testis 1293
Sperm Develop as a Syncytium 1294
Summary 1296
FERTILIZATION 1297
Ejaculated Sperm Become Capacitated in the Female Genital Tract 1297
Capacitated Sperm Bind to the Zona Pellucida and Undergo an
Acrosome Reaction 1298
The Mechanism of Sperm-Egg Fusion Is Still Unknown 1298
Sperm Fusion Activates the Egg by Increasing Ca2+ in the
Cytosol 1299
The Cortical Reaction Helps Ensure That Only One Sperm
Fertilizes the Egg 1300
The Sperm Provides Centrioles as Well as Its Genome to the
Zygote 1301
IVF and ICSI Have Revolutionized the Treatment of Human
Infertility 1301
Summary 1303
References 1304
Chapter 22 Development of Multicellular
Organisms 1305
UNIVERSAL MECHANISMS OF ANIMAL DEVELOPMENT 1305
Animals Share Some Basic Anatomical Features 1307
Multicellular Animals Are Enriched in Proteins Mediating Cell
Interactions and Gene Regulation 1308
Regulatory DNA Defines the Program of Development 1309
Manipulation of the Embryo Reveals the Interactions Between
Its Cells 1310
Studies of Mutant Animals Identify the Genes That Control
Developmental Processes 1311
A Cell Makes Developmental Decisions Long Before It Shows
a Visible Change 1311
Cells Have Remembered Positional Values That Reflect Their
Location in the Body 1312
Inductive Signals Can Create Orderly Differences Between
Initially Identical Cells 1313
Sister Cells Can Be Born Different by an Asymmetric Cell
Division 1313
Positive Feedback Can Create Asymmetry Where There Was
None Before 1314
Positive Feedback Generates Patterns, Creates AII-or-None
Outcomes, and Provides Memory 1315
A Small Set of Signaling Pathways, Used Repeatedly, Controls
Developmental Patterning 1316
Morphogens Are Long-Range InducersThat Exert Graded Effects 1316
Extracellular Inhibitors of Signal Molecules Shape the Response
tothelnducer 1317
Developmental Signals Can Spread Through Tissue in Several
Different Ways 1318
Programs That Are Intrinsic to a Cell Often Define the Time-Course
of its Development 1319
Initial Patterns Are Established in Small Fields of Cells and
Refined by Sequential Induction as the Embryo Grows 1319
Summary 1320
CAENORHABDITIS ELEGANS: DEVELOPMENT FROM THE
PERSPECTIVE OF THE INDIVIDUAL CELL
Caenorhabditis elegans Is Anatomically Simple
Cell Fates in the Developing Nematode Are Almost Perfectly
Predictable
Products of Maternal-Effect Genes Organize the Asymmetric
Division of the Egg
Progressively More Complex Patterns Are Created by Cell-Cell
Interactions
Microsurgery and Genetics Reveal the Logic of Developmental
Control; Gene Cloning and Sequencing Reveal Its Molecular
Mechanisms
Cells Change Over Time in Their Responsiveness to
Developmental Signals
Heterochronic Genes Control the Timing of Development
Cells Do Not Count Cell Divisions in Timing Their Internal
Programs
Selected Cells Die by Apoptosis as Part of the Program of
Development
Summary
DROSOPHILA AND THE MOLECULAR GENETICS OF
PATTERN FORMATION: GENESIS OF THE BODY PLAN
1321
1321
1322
1323
1324
1325
1325
1326
1327
1327
1328
1328
1329
1330
The Insect Body Is Constructed as a Series of Segmental Units
Drosophila Begins Its Development as a Syncytium
Genetic Screens Define Groups of Genes Required for Specific
Aspects of Early Patterning 1332
Interactions of theOocyte With Its Surroundings Define the
Axes of the Embryo: the Role of the Egg-Polarity Genes 1333
The Dorsoventral Signaling Genes Create a Gradient of a
Nuclear Gene Regulatory Protein 1334
Dpp and Sog Set Up a Secondary Morphogen Gradient to
Refine the Pattern of the Dorsal Part of the Embryo 1336
The Insect Dorsoventral Axis Corresponds to the Vertebrate
Ventrodorsal Axis 1336
Three Classes of Segmentation Genes Refine the Anterior-Posterior
Maternal Pattern and Subdivide the Embryo 1336
The Localized Expression of Segmentation Genes Is Regulated
by a Hierarchy of Positional Signals 1337
The Modular Nature of Regulatory DNA Allows Genes to Have
Multiple Independently Controlled Functions 1339
Egg-Polarity, Gap, and Pair-Rule Genes Create a Transient
Pattern That Is Remembered by Other Genes 1340
Summary 1341
HOMEOTIC SELECTOR GENES AND THE PATTERNING OF
THE ANTEROPOSTERIOR AXIS 1341
The Hox Code Specifies Anterior-Posterior Differences 1342
Homeotic Selector Genes Code for DNA-Binding Proteins That
Interact with Other Gene Regulatory Proteins 1342
The Homeotic Selector Genes Are Expressed Sequentially
According to Their Order in the Hox Complex 1343
The Hox Complex Carries a Permanent Record of Positional
Information 1344
The Anteroposterior Axis Is Controlled by Hox Selector Genes in
Vertebrates Also 1344
Summary 1347
ORGANOGENESIS AND THE PATTERNING OF
APPENDAGES 1347
Conditional and Induced Somatic Mutations Make it Possible to
Analyze Gene Functions Late in Development 1348
Body Parts of the Adult Fly Develop From Imaginal Discs 1349
Homeotic Selector Genes Are Essential for the Memory of
Positional Information in Imaginal Disc Cells 1351
Specific Regulatory Genes Define the Cells That Will Form an
Appendage 1351
The Insect Wing Disc Is Divided into Compartments 1352
Four Familiar Signaling Pathways Combine to Pattern the
Wing Disc: Wingless, Hedgehog, Dpp, and Notch 1353
The Size of Each Compartment Is Regulated by Interactions
Among Its Cells 1353
Similar Mechanisms Pattern the Limbs of Vertebrates 1355
Localized Expression of Specific Classes of Gene Regulatory
Proteins Foreshadows Cell Differentiation 1356
Lateral Inhibition Singles Out Sensory Mother Cells Within
Proneural Clusters 1357
Lateral Inhibition Drives the Progeny of the Sensory Mother Cell
Toward Different Final Fates 1357
Planar Polarity of Asymmetric Divisions is Controlled by Signaling
via the Receptor Frizzled 1358
Asymmetric Stem-Cell Divisions Generate Additional Neurons
in the Central Nervous System 1359
Asymmetric Neuroblast Divisions Segregate an Inhibitor of Cell
Division into Just One of the Daughter Cells 1361
Notch Signaling Regulates the Fine-Grained Pattern of
Differentiated Cell Types in Many Different Tissues 1362
Some Key Regulatory Genes Define a Cell Type; Others Can
Activate the Program for Creation of an Entire Organ 1362
Summary 1363
CELL MOVEMENTS AND THE SHAPING OF THE
VERTEBRATE BODY
1363
The Polarity of the Amphibian Embryo Depends on the Polarity
of the Egg 1364
Cleavage Produces Many Cells from One 1365
Gastrulation Transforms a Hollow Ball of Cells into a Three-Layered
Structure with a Primitive Gut 1365
The Movements of Gastrulation Are Precisely Predictable 1366
Chemical Signals Trigger the Mechanical Processes 1367
Active Changes of Cell Packing Provide a Driving Force for
Gastrulation 1368
Changing Patterns of Cell Adhesion Molecules Force Cells
Into New Arrangements 1369
The Notochord Elongates, While the Neural Plate Rolls Up to
Form the Neural Tube 1370
A Gene-Expression Oscillator Controls Segmentation of the
Mesoderm Into Somites 1371
Delayed Negative Feedback May Generate the Oscillations
of the Segmentation Clock 1373
Embryonic Tissues Are Invaded in a Strictly Controlled Fashion
by Migratory Cells 1373
The Distribution of Migrant Cells Depends on Survival Factors
as Well as Guidance Cues 1375
Left-Right Asymmetry of the Vertebrate Body Derives From
Molecular Asymmetry in the Early Embryo 1376
Summary 1377
THE MOUSE 1378
Mammalian Development Begins With a Specialized Preamble 1378
The Early Mammalian Embryo Is Highly Regulative 1380
Totipotent Embryonic Stem Cells Can Be Obtained From a
Mammalian Embryo 1380
Interactions Between Epithelium and Mesenchyme Generate
Branching Tubular Structures 1381
Summary 1382
NEURAL DEVELOPMENT 1383
Neurons Are Assigned Different Characters According to the
Time and Place Where They Are Born 1383
The Character Assigned to a Neuron at Its Birth Governs the
Connections It Will Form 1385
Each Axon or Dendrite Extends by Means of a Growth Cone at
Its Tip 1386
The Growth Cone Pilots the Developing Neurite Along a Precisely
Defined Path In Vivo 1387
Growth Cones Can Change Their Sensibilities asThey Travel 1389
Target Tissues Release Neurotrophic Factors That Control Nerve
Cell Growth and Survival 1389
Neuronal Specificity Guides the Formation of Orderly Neural
Maps 1391
Axons From Different Regions of the Retina Respond Differently
to a Gradient of Repulsive Molecules in theTectum 1392
Diffuse Patterns of Synaptic Connections Are Sharpened by
Activity-Dependent Remodeling 1393
Experience Molds the Pattern of Synaptic Connections in the
Brain 1395
Adult Memory and Developmental Synapse Remodeling May
Depend on Similar Mechanisms 1396
Summary 1397
PLANT DEVELOPMENT 1398
Arabidopsis Serves as a Model Organism for Plant Molecular
Genetics 1398
The Arabidopsis Genome Is Rich in Developmental Control
Genes 1399
Embryonic Development Starts by Establishing a Root-Shoot
Axis and Then Halts Inside the Seed 1400
The Parts of a Plant Are Generated Sequentially by Meristems 1403
Development of the Seedling Depends on Environmental Signals 1403
Long-Range Hormonal Signals Coordinate Developmental Events
in Separate Parts of the Plant 1403
The Shaping of Each New Structure Depends on Oriented
Cell Division and Expansion 1406
Each Plant Module Grows From a Microscopic Set of Primordia
in a Meristem 1407
Polarized Auxin Transport Controls the Pattern of Primordia
in the Meristem 1408
Cell Signaling Maintains the Meristem 1409
Regulatory Mutations Can Transform Plant Topology by
Altering Cell Behavior in the Meristem 1410
The Switch to Flowering Depends on Past and Present
Environmental Cues 1412
Homeotic Selector Genes Specify the Partsofa Flower 1413
Summary 1415
References 1415
Chapter 23 Specialized Tissues, Stem Cells,
and Tissue Renewal 1417
EPIDERMIS AND ITS RENEWAL BY STEM CELLS 1417
Epidermal Cells Form a Multilayered Waterproof Barrier 1419
Differentiating Epidermal Cells Express a Sequence of Different
Genes as They Mature 1420
Stem Cells in the Basal Layer Provide for Renewal of the Epidermis 1420
The Two Daughters of a Stem Cell Do Not Always Have to
Become Different 1421
The Basal Layer Contains Both Stem Cells and Transit Amplifying
Cells 1422
Transit amplifying Divisions Are Part of the Strategy of Growth
Control 1423
Stem Cells of Some Tissues Selectively Retain Original DNA
Strands 1424
The Rate of Stem-Cell Division Can Increase Dramatically
When New Cells Are Needed Urgently 1425
Many Interacting Signals Govern Epidermal Renewal 1426
The Mammary Gland Undergoes Cycles of Development and
Regression 1426
Summary 1428
SENSORY EPITHELIA 1429
Olfactory Sensory Neurons Are Continually Replaced 1429
Auditory Hair Cells Have to Last a Lifetime 1430
Most Permanent Cells Renew Their Parts: the Photoreceptor
Cells of the Retina 1432
Summary 1433
THE AIRWAYS AND THE GUT 1434
Adjacent Cell Types Collaborate in the Alveoli of the Lungs 1434
Goblet Cells, Ciliated Cells, and Macrophages Collaborate to
Keep the Airways Clean 1434
The Lining of the Small Intestine Renews Itself Faster Than
Any Other Tissue 1436
Wnt Signaling Maintains the Gut Stem-Cell Compartment 1438
Notch Signaling Controls Gut Cell Diversification 1439
Ephrin-Eph Signaling Controls the Migrations of Gut Epithelial
Cells 1440
Wnt, Hedgehog, PDGF, and BMP Signaling Pathways Combine
to Delimit the Stem-Cell Niche 1441
The Liver Functions as an Interface Between the Digestive Tract
and the Blood 1442
Liver Cell Loss Stimulates Liver Cell Proliferation 1443
Tissue Renewal Does Not Have to Depend on Stem Cells: Insulin-
Secreting Cells in the Pancreas 1444
Summary 1445
BLOODVESSELS, LYMPHATICS, AND ENDOTHELIAL
CELLS 1445
Endothelial Cells Line All Bloodvessels and Lymphatics 1445
Endothelial Tip Cells Pioneer Angiogenesis 1446
Different Types of Endothelial Cells Form Different Types of Vessel 1447
Tissues Requiring a Blood Supply Release VEGF; Notch Signaling
Between Endothelial Cells Regulates the Response 1448
Signals from Endothelial Cells Control Recruitment of Pericytes
and Smooth Muscle Cells to Form the Vessel Wall 1450
Summary 1450
RENEWAL BY MULTIPOTENT STEM CELLS: BLOOD CELL
FORMATION 1450
The Three Main Categories of White Blood Cells Are Granulocytes,
Monocytes, and Lymphocytes 1451
The Production of Each Type of Blood Cell in the Bone Marrow Is
Individually Controlled 1453
Bone Marrow Contains Hemopoietic Stem Cells 1454
A Multipotent Stem Cell Gives Rise to All Classes of Blood Cells 1456
Commitment Is a Stepwise Process 1456
Divisions of Committed Progenitor Cells Amplify the Number of
Specialized Blood Cells 1457
Stem Cells Depend on Contact Signals From Stromal Cells 1458
Factors That Regulate Hemopoiesis Can Be Analyzed in Culture 1459
Erythropoiesis Depends on the Hormone Erythropoietin 1459
Multiple CSFs Influence Neutrophil and Macrophage Production 1460
The Behavior of a Hemopoietic Cell Depends Partly on Chance 1461
Regulation of Cell Survival Is as Important as Regulation of Cell
Proliferation 1462
Summary 1462
GENESIS, MODULATION, AND REGENERATION OF
SKELETAL MUSCLE 1463
Myoblasts Fuse to Form New Skeletal Muscle Fibers 1464
Muscle Cells Can Vary Their Properties by Changing the Protein
Isoforms They Contain 1465
Skeletal Muscle Fibers Secrete Myostatin to Limit Their Own Growth 1465
Some Myoblasts Persist as Quiescent Stem Cells in the Adult 1466
Summary 1467
FIBROBLASTS AND THEIR TRANSFORMATIONS: THE
CONNECTIVE-TISSUE CELL FAMILY 1467
Fibroblasts Change Their Character in Response to Chemical
Signals 1467
The Extracellular Matrix May Influence Connective-Tissue Cell
Differentiation by Affecting Cell Shape and Attachment 1468
Osteoblasts Make Bone Matrix 1469
Most Bones Are Built Around Cartilage Models 1470
Bone Is Continually Remodeled by the Cells Within It 1472
Osteoclasts Are Controlled by Signals From Osteoblasts 1473
Fat Cells Can Develop From Fibroblasts 1474
Leptin Secreted by Fat Cells Provides Feedback to Regulate
Eating 1475
Summary 1476
STEM-CELL ENGINEERING 1476
Hemopoietic Stem Cells Can Be Used to Replace Diseased Blood
Cells with Healthy Ones 1477
Epidermal Stem Cell Populations Can Be Expanded in Culture for
Tissue Repair 1477
Neural Stem Cells Can Be Manipulated in Culture 1478
Neural Stem Cells Can Repopulate the Central Nervous System 1478
Stem Cells in the Adult Body Are Tissue-Specific 1479
ES Cells Can Make Any Part of the Body 1480
Patient-Specific ES Cells Could Solve the Problem of Immune
Rejection 1481
ES Cells Are Useful for Drug Discovery and Analysis of Disease 1482
Summary 1482
References 1483
Chapter 24 Pathogens, Infection, and Innate
Immunity 1485
INTRODUCTION TO PATHOGENS 1486
Pathogens Have Evolved Specific Mechanisms for Interacting
with Their Hosts 1486
The Signs and Symptoms of Infection May Be Caused by the
Pathogen or by the Host's Responses 1487
Pathogens Are Phylogenetically Diverse 1488
Bacterial Pathogens Carry Specialized Virulence Genes 1489
Fungal and Protozoan Parasites Have Complex Life Cycles with
Multiple Forms 1494
All Aspects of Viral Propagation Depend on Host Cell Machinery 1496
Prions Are Infectious Proteins 1498
Infectious Disease Agents Are Linked To Cancer, Heart Disease,
and Other Chronic Illnesses 1499
Summary 1501
CELL BIOLOGY OF INFECTION 1501
Pathogens Cross Protective Barriers to Colonize the Host 1501
Pathogens That Colonize Epithelia Must Avoid Clearance by
the Host 1502
Intracellular Pathogens Have Mechanisms for Both Entering
and Leaving Host Cells 1504
Virus Particles Bind to Molecules Displayed on the Host Cell
Surface 1505
Virions Enter Host Cells by Membrane Fusion, Pore Formation, or
Membrane Disruption 1506
Bacteria Enter Host Cells by Phagocytosis 1507
Intracellular Eucaryotic Parasites Actively Invade Host Cells 1508
Many Pathogens Alter Membrane Traffic in the Host Cell 1511
Viruses and Bacteria Use the Host Cell Cytoskeleton for Intracellular
Movement 1514
Viral Infections Take Over the Metabolism of the Host Cell 1517
Pathogens Can Alter the Behavior of the Host Organism to Facilitate
the Spread of the Pathogen 1518
Pathogens Evolve Rapidly 1518
Antigenic Variation in Pathogens Occurs by Multiple
Mechanisms 1519
Error-Prone Replication Dominates Viral Evolution 1520
Drug-Resistant Pathogens Are a Growing Problem 1521
Summary 1524
BARRIERS TO INFECTION AND THE INNATE IMMUNE
SYSTEM 1524
Epithelial Surfaces and Defensins Help Prevent Infection 1525
Human Cells Recognize Conserved Features of Pathogens 1526
Complement Activation Targets Pathogens for Phagocytosis
or Lysis 1528
Toll-like Proteins and NOD Proteins Are an Ancient Family of
Pattern Recognition Receptors 1530
Phagocytic Cells Seek, Engulf, and Destroy Pathogens 1531
Activated Macrophages Contribute to the Inflammatory
Response at Sites of Infection 1533
Virus-Infected Cells Take Drastic Measures to Prevent Viral
Replication 1534
Natural Killer Cells Induce Virus-Infected Cells to Kill Themselves 1535
Dendritic Cells Provide the Link Between the Innate and
Adaptive Immune Systems 1536
Summary 1537
References 1537
Chapter 25 The Adaptive Immune System 1539
LYMPHOCYTES AND THE CELLULAR BASIS OF ADAPTIVE
IMMUNITY 1540
Lymphocytes Are Required for Adaptive Immunity 1540
The Innate and Adaptive Immune Systems Work Together 1541
B Lymphocytes Develop in the Bone Marrow; T Lymphocytes
Develop in the Thymus 1543
The Adaptive Immune System Works by Clonal Selection 1544
Most Antigens Activate Many Different Lymphocyte Clones 1545
Immunological Memory Involves Both Clonal Expansion and
Lymphocyte Differentiation 1545
Immunological Tolerance Ensures That Self Antigens Are Not
Normally Attacked 1547
Lymphocytes Continuously Circulate Through Peripheral
Lymphoid Organs 1549
Summary 1551
B CELLS AND ANTIBODIES 1551
B Cells Make Antibodies as Both Cell-Surface Antigen Receptors
and Secreted Proteins 1552
A Typical Antibody Has Two Identical Antigen-Binding Sites 1552
An Antibody Molecule Is Composed of Heavy and Light Chains 1552
There Are Five Classes of Antibody Heavy Chains, Each with
Different Biological Properties 1553
The Strength of an Antibody-Antigen Interaction Depends on
Both the Number and the Affinity of the Antigen-Binding
Sites 1557
Antibody Light and Heavy Chains Consist of Constant and Variable
Regions 1558
The Light and Heavy Chains Are Composed of Repeating Ig
Domains 1559
An Antigen-Binding Site Is Constructed from Hypervariable Loops 1560
Summary 1561
THE GENERATION OF ANTIBODY DIVERSITY 1562
Antibody Genes Are Assembled From Separate Gene Segments
During B Cell Development 1562
Imprecise Joining of Gene Segments Greatly Increases the
Diversity of V Regions 1564
The Control of V(D)J Recombination Ensures That B Cells Are
Monospecific 1565
Antigen-Driven Somatic Hypermutation Fine-Tunes Antibody
Responses 1566
B Cells Can Switch the Class of Antibody They Make 1567
Summary 1568
T CELLS AND MHC PROTEINS 1569
TCell Receptors (TCRs) Are Antibodylike Heterodimers 1570
Antigen Presentation by Dendritic Cells Can Either Activate
orTolerizeT Cells 1571
Effector Cytotoxic T Cells Induce Infected Target Cells to
Kill Themselves 1572
Effector Helper T Cells Help Activate Other Cells of the Innate
and Adaptive Immune Systems 1573
Regulatory T Cells Suppress the Activity of Other T Cells 1574
T Cells Recognize Foreign Peptides Bound to MHC Proteins 1575
MHC Proteins Were Identified in Transplantation Reactions
Before Their Functions Were Known 1575
Class I and Class II MHC Proteins Are Structurally Similar
Heterodimers 1576
An MHC Protein Binds a Peptide and Interacts with a
T Cell Receptor 1577
MHC Proteins Help Direct T Cells to Their Appropriate Targets 1579
CD4 and CD8 Co-Receptors Bind to Invariant Parts of MHC
Proteins 1580
Cytotoxic T Cells Recognize Fragments of Foreign Cytosolic
Proteins in Association with Class I MHC Proteins 1581
Helper T Cells Respond to Fragments of Endocytosed Foreign
Protein Associated with Class II MHC Proteins 1583
Potentially Useful T Cells Are Positively Selected in theThymus 1585
Most Developing Cytotoxic and Helper T Cells That Could
Be Activated by Self-Peptide-MHC Complexes Are Eliminated
in theThymus 1586
Some Organ-Specific Proteins Are Ectopically Expressed in the
Thymus Medulla 1587
The Function of MHC Proteins Helps Explain Their Polymorphism 1588
Summary 1588
HELPER T CELLS AND LYMPHOCYTE ACTIVATION 1589
Activated Dendritic Cells Use Multiple Mechanisms to
Activate T Cells 1590
The Activation ofT Cells Is Controlled by Negative Feedback 1591
The Subclass of Effector Helper T Cell Determines the Nature
of the Adaptive Immune Response 1592
Th1 Cells Activate Infected Macrophages and Stimulate An
Inflammatory Response 1594
Antigen Binding to B Cell Receptors (BCRs) Is Only One Step in
B Cell Activation 1595
Antigen-Specific HelperT Cells Are Essential for Activating Most
B Cells 1597
A Special Class of B Cells Recognize T-Cell-lndependent Antigens 1598
Immune Recognition Molecules Belong to the Ancient Ig
Superfamily 1599
Summary 1600
References 1600 |
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| callnumber-raw | QH581.2 |
| callnumber-search | QH581.2 |
| callnumber-sort | QH 3581.2 |
| callnumber-subject | QH - Natural History and Biology |
| classification_rvk | WD 4150 WE 1000 WE 2400 |
| classification_tum | BIO 200f |
| ctrlnum | (OCoLC)82673690 (DE-599)BVBBV023058513 |
| dewey-full | 571.6 |
| dewey-hundreds | 500 - Natural sciences and mathematics |
| dewey-ones | 571 - Physiology & related subjects |
| dewey-raw | 571.6 |
| dewey-search | 571.6 |
| dewey-sort | 3571.6 |
| dewey-tens | 570 - Biology |
| discipline | Biologie |
| discipline_str_mv | Biologie |
| edition | 5. ed., reference ed. |
| format | Book |
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| genre | 1\p (DE-588)4123623-3 Lehrbuch gnd-content |
| genre_facet | Lehrbuch |
| geographic | Aphrodisias (DE-588)4002418-0 gnd Altleiningen (DE-588)4001534-8 gnd |
| geographic_facet | Aphrodisias Altleiningen |
| id | DE-604.BV023058513 |
| illustrated | Illustrated |
| index_date | 2024-07-02T19:27:45Z |
| indexdate | 2024-07-09T21:10:01Z |
| institution | BVB |
| isbn | 0815341113 9780815341116 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-016261777 |
| oclc_num | 82673690 |
| open_access_boolean | |
| owner | DE-91G DE-BY-TUM DE-355 DE-BY-UBR DE-703 DE-M49 DE-BY-TUM DE-19 DE-BY-UBM DE-83 DE-188 |
| owner_facet | DE-91G DE-BY-TUM DE-355 DE-BY-UBR DE-703 DE-M49 DE-BY-TUM DE-19 DE-BY-UBM DE-83 DE-188 |
| physical | Getr. Zählung zahlr. Ill., graph. Darst. 1 DVD-ROM (12 cm) |
| publishDate | 2008 |
| publishDateSearch | 2008 |
| publishDateSort | 2008 |
| publisher | Garland Science |
| record_format | marc |
| spelling | Molecular biology of the cell Bruce Alberts ... The cell 5. ed., reference ed. New York [u.a.] Garland Science 2008 Getr. Zählung zahlr. Ill., graph. Darst. 1 DVD-ROM (12 cm) txt rdacontent n rdamedia nc rdacarrier cellular biology cabt molecular biology cabt Cells cabt genetics cabt molecular genetics cabt signal transduction cabt Biologia molecular larpcal Citologia larpcal Cytology Molecular biology Molekularbiologie (DE-588)4039983-7 gnd rswk-swf Cytologie (DE-588)4070177-3 gnd rswk-swf Zelle (DE-588)4067537-3 gnd rswk-swf Aphrodisias (DE-588)4002418-0 gnd rswk-swf Altleiningen (DE-588)4001534-8 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 Alberts, Bruce 1938- Sonstige (DE-588)111053013 oth http://www.loc.gov/catdir/toc/ecip0710/2007005476.html Table of contents only HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=016261777&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 | Molecular biology of the cell cellular biology cabt molecular biology cabt Cells cabt genetics cabt molecular genetics cabt signal transduction cabt Biologia molecular larpcal Citologia larpcal Cytology Molecular biology Molekularbiologie (DE-588)4039983-7 gnd Cytologie (DE-588)4070177-3 gnd Zelle (DE-588)4067537-3 gnd |
| subject_GND | (DE-588)4039983-7 (DE-588)4070177-3 (DE-588)4067537-3 (DE-588)4002418-0 (DE-588)4001534-8 (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_exact_search_txtP | Molecular biology of the cell |
| title_full | Molecular biology of the cell Bruce Alberts ... |
| title_fullStr | Molecular biology of the cell Bruce Alberts ... |
| title_full_unstemmed | Molecular biology of the cell Bruce Alberts ... |
| title_short | Molecular biology of the cell |
| title_sort | molecular biology of the cell |
| topic | cellular biology cabt molecular biology cabt Cells cabt genetics cabt molecular genetics cabt signal transduction cabt Biologia molecular larpcal Citologia larpcal Cytology Molecular biology Molekularbiologie (DE-588)4039983-7 gnd Cytologie (DE-588)4070177-3 gnd Zelle (DE-588)4067537-3 gnd |
| topic_facet | cellular biology molecular biology Cells genetics molecular genetics signal transduction Biologia molecular Citologia Cytology Molecular biology Molekularbiologie Cytologie Zelle Aphrodisias Altleiningen Lehrbuch |
| url | http://www.loc.gov/catdir/toc/ecip0710/2007005476.html http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=016261777&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT albertsbruce molecularbiologyofthecell AT albertsbruce thecell |