essential cell biology

second edition

Bruce Alberts Dennis Bray Karen Hopkin Alexander Johnson Julian Lewis Martin Raff Keith Roberts Peter Walter

Garland Science
Taylor & Francis Group

Contents and Special Features

Chapter 1
Panel 1-1 Panel 1-2 How We Know Chapter 2 How We Know Panel 2-1 Panel 2-2 Panel 2-3 Panel 2-4 Panel 2-5 Panel 2-6 Panel 2-7

Introduction to Cells Light and electron microscopy Cells: the principal features of animal, plant, and bacterial cells Life's common mechanisms Chemical Components of Cells What are macromolecules? Chemical bonds and groups The chemical properties of water An outline of some of the types of sugars Fatty acids and other lipids The 20 amino acids found in proteins A survey of the nucleotides The principal types of weak noncovalent bonds Energy, Catalysis, and Biosynthesis Free energy and biological reactions Using kinetics to model and manipulate metabolic pathways Protein Structure and Function A few examples of some general protein functions Probing protein structure Four different ways of depicting a small protein Cell breakage and initial fractionation of cell extracts Protein separation by chromatography Protein separation by electrophoresis Making and using antibodies DNA and Chromosomes Genes are made of DNA DNA Replication, Repair, and Recombination Finding replication origins From DNA to Protein: How Cells Read the Genome Cracking the genetic code Control of Gene Expression Gene regulationthe story of eve How Genes and Genomes Evolve Counting genes

1
8 25 30

39
60 66 68 70 72 74 76 78

Chapter 3
Panel 3-1 How We Know Chapter 4 Panel4-1 How We Know Panel 4-2 Panel 4-3 ; Panel 4-4 Panel 4-5 Panel 4-6

83
96 103 119
120 129 132 160 162 163 164

Chapter 5
How We Know Chapter 6 How We Know Chapter 7 How We Know Chapter 8 How We Know Chapter 9 How We Know

169 172 195 198 229

246

267
282

293 314

ix

Chapter 10 How We Know Chapter 11

How We Know

Manipulating Genes and Cells

Sequencing the human genome

323
334

Membrane Structure
Measuring membrane flow Membrane Transport Squid reveal secrets of membrane excitability

365
384

Chapter 12
How We Know

389 414 427

432 442 450

Chapter 13
Panel 13-1 How We Know Panel 13-2

How Cells Obtain Energy from Food

Details of the 10 steps of glycolysis Unraveling the citric acid cycle The complete citric acid cycle Energy Generation in Mitochondria and Chloroplasts How chemiosmotic coupling drives ATP synthesis Redox potentials Intracellular Compartments and Transport
Tracking protein and vesicle transport

Chapter 14
How We Know Panel 14-1 Chapter 15 How We Know Chapter-16
How We Know

453
460 471 497
520

Cell Communication
Untangling cell signaling pathways Cytoskeleton Pursuing motor proteins

533
561 573
586

Chapter 17
How We Know

Chapter 18 How We Know

Cell-Cycle Control and Cell Death

Discovery of cyclins and Cdks Cell Division The principal ^stages of M phase in an animal cell Building the mitotic spindle

611 618 637

642 646

Chapter 19
Panel 19-1 How We Know Chapter 20 How We Know Panel 20-1 Chapter 21 Panel 21-1 How We Know

Genetics, Meiosis, and the Molecular Basis of Heredity

Reading genetic linkage maps Some essentials of classical genetics Tissues and Cancer The cell types and tissues from which higher plants are constructed Making sense of the genes that are critical for cancer

659
682 685

697
700 734

Answers to Questions Glossary Index 1:1

Contents and Special Features

Detailed Contents

Chapter 1

Introduction to Cells
1
2 3 4 5 5 6 7 11 14 15 16 16 Mitochondria Generate Energy from Food to Power the Cell Chloroplasts Capture Energy from Sunlight Internal Membranes Create Intracellular Compartments with Different Functions ,' The Cytosol Is a Concentrated Aqueous Gel of Large and Small Molecules The Cytoskeleton Is Responsible for Directed Cell Movements The Cytoplasm Is Far from Static Eucaryotic Cells May Have Originated as Predators M o d e l Organisms Molecular Biologists Have Focused on E. co// Brewer's Yeast Is a Simple Eucaryotic Cell Arabidopsis Has Been Chosen Out of 300,000 Species as a Model Plant The World of Animals Is Represented by a Fly, a Worm, a Mouse, and Homo sapiens Comparing Genome Sequences Reveals Life's Common Heritage 17 18 19 22 22 23 24 27 28 28 28 29 33

Unity and Diversity of Cells

Cells Vary Enormously in Appearance and Function Living Cells All Have a Similar Basic Chemistry All Present-Day Cells Have Apparently Evolved from the Same Ancestor Genes Provide the Instructions for Cellular Form, Function, and Complex Behavior Cells Under the Microscope The Invention of the Light Microscope Led to the Discovery of Cells Cells, Organelles, and Even Molecules Can Be Seen Under the Microscope The Procaryotic Cell Procaryotes Are the Most Diverse of Cells The World of Procaryotes Is Divided into Two Domains: Eubacteria and Archaea
p

The Eucaryotic Cell The Nucleus Is the Information Store of the Cell

Chapter 2
Chemical Bonds

Chemical Components of Cells

39
40 41 43 45 46 47 48 49 50 50

39

Cells Are Made of Relatively Few Types of Atoms The Outermost Electrons Determine How Atoms Interact . Ionic Bonds Form by the Gain and Loss of Electrons Covalent Bonds Form by the Sharing of Electrons Covalent Bonds Vary in Strength There Are Different Types of Covalent Bonds Water Is Held Together by Hydrogen Bonds Some Polar Molecules Form Acids and Bases in Water Molecules in Cells A Cell Is Formed from Carbon Compounds

Cells Contain Four Major Families of Small Organic Molecules 51 Sugars Are Energy Sources for Cells and Subunits of Polysaccharides 52 Fatty Acids Are Components of Cell Membranes 53 Amino Acids Are the Subunits of Proteins 55 Nucleotides Are the Subunits of DNA and RNA 56 Macromolecules in Cells Macromolecules Contain a Specific Sequence of Subunits Noncovalent Bonds Specify the Precise Shape of a Macromolecule Noncovalent Bonds Allow a Macromolecule to Bind Other Selected Molecules 58 59 62 63

Detailed Contents

Chapter 3

Energy, Catalysis, and Biosynthesis

84
85 88 89 90 91 93 Rapid Diffusion Allows Enzymes to Find Their Substrates and KM Measure Enzyme Performance

83
100 101

Catalysis and the Use of Energy by Cells

Biological Order Is Made Possible by the Release of Heat Energy from Cells Photosynthetic Organisms Use Sunlight to Synthesize Organic Molecules Cells Obtain Energy by the Oxidation of Organic Molecules Oxidation and Reduction Involve Electron Transfers Enzymes Lower the Barriers That Block Chemical Reactions The Free-Energy Change for a Reaction Determines Whether It Can Occur The Concentration of Reactants Influences the Free-Energy Change and a Reaction's Direction The Equilibrium Constant Indicates the Strength of Molecular Interactions For Sequential Reactions, the Changes in Free Energy Are Additive

Activated Carrier Molecules and Biosynthesis

The Formation of an Activated Carrier Is Coupled to an Energetically Favorable Reaction ATP Is the Most Widely Used Activated Carrier Molecule Energy Stored in ATP Is Often Harnessed to Join two Molecules Together NADH and NADPH Are Important Electron Carriers There Are Many Other Activated Carrier Molecules in Cells The Synthesis of Biological Polymers Requires an Energy Input

106

106 107 108 109 111 112

94 95 98

Chapter 4

Protein Structure and Function

119
121 124 125 126 134 135 136 137 138 139 140 141 142

119
143 143 144 145 146 149

The Shape and Structurenof Proteins

The Shape of a Protein Is Specified by Its Amino Acid Sequence Proteins Fold into a Conformation of Lowest Energy , ( Proteins Come in a Wide Variety of Complicated Shapes The a Helix and the p Sheet Are Common Folding Patterns Helices Form Readily in Biological Structures P Sheets Form Rigid Structures at the Core of Many Proteins Proteins Have Several Levels of Organization Few of the Many Possible Polypeptide Chains Will Be Useful Proteins Can Be Classified into Families Large Protein Molecules Often Contain More Than One Polypeptide Chain Proteins Can Assemble into Filaments, Sheets, or Spheres Some Types of Proteins Have Elongated Fibrous Shapes Extracellular Proteins Are Often Stabilized by Covalent Cross-Linkages

How Proteins Work

All Proteins Bind to Other Molecules The Binding Sites of Antibodies Are Especially Versatile Enzymes Are Powerful and Highly Specific Catalysts Lysozyme Illustrates How an Enzyme Works Tightly Bound Small Molecules Add Extra Functions to Proteins

How Proteins Are Controlled 150 The Catalytic Activities of Enzymes Are Often 151 Regulated by Other Molecules Allosteric Enzymes Have Two Binding Sites That 151 Influence One Another Phosphorylation Can Control Protein Activity 153 by Triggering a Conformational Change GTP-Binding Proteins Are Also Regulated by the 154 Cyclic Gain and Loss of a Phosphate Group Nucleotide Hydrolysis Allows Motor Proteins to 155 Produce Large Movements in Cells Proteins Often Form Large Complexes That 156 Function as Protein Machines Large-Scale Studies of Protein Structure and Function Are Increasing the Pace of Discovery 157

Chapter 5

DNA and Chromosomes

170
Interphase Chromosomes Are Organized Within the Nucleus The DNA in Chromosomes Is Highly Condensed, Nucleosomes Are the Basic Units of Chromatin Structure Chromosomes Have Several Levels of DNA Packing Interphase Chromosomes Contain Both Condensed and More Extended Forms of Chromatin Changes in Nucleosome Structure Allow Access to DNA

169
183 183 184 186

The Structure and Function of DNA

A DNA Molecule Consists of Two Complementary Chains of Nucleotides 171 The Structure of DNA Provides a Mechanism for Heredity 176 The Structure, of Eucaryotic Chromosomes Eucarydtic DNA Is Packaged into Chromosomes Chromosomes Contain Long Strings of Genes Chromosomes Exist in Different States Throughout the Life of a Cell 177 178 179 181

187 189

Chapter 6
DNA Replication

DNA Replication, Repair, and Recombination

196
196 197 201 202 203 204 206 207 208 209 209 DNA Is Continually Suffering Damage in Cells The Stability of Genes Depends on DNA Repair The High Fidelity of DNA Maintenance Allows Closely Related Species to Have Proteins with Very Similar Sequences DNA Recombination Homologous Recombination Results in an Exact Exchange of Genetic Information Recombination Can Also Occur Between Nonhomologous DNA Sequences Mobile Genetic Elements Encode the Components They Need for Movement A Large Fraction of the Human Genome Is Composed of Two Families of Transposable Sequences Viruses Are Fully Mobile Genetic Elements That Can Escape from Cells Retroviruses Reverse the Normal Flow of Genetic Information

195
212 213

Base-Pairing Enables DNA Replication DNA Synthesis Begins at Replication Origins New DNA Synthesis Occurs at Replication Forks The Replication Fork Is Asymmetrical DNA Polymerase Is Self-correcting Short Lengths of RNA Act as Primers for DNA Synthesis Proteins a t a Replication Fork Cooperate to Form a Replication Machine Telomerase Replicates the Ends of Eucaryotic Chromosomes DNA Replication Is Relatively Well Understood DNA Repair Mutations Can Have Severe Consequences for an Organism A DNA Mismatch Repair System Removes Replication Errors That Escape the Replication Machine

214 215 215 216 217

218 219 221

210

Detailed Contents

XIII

Chapter 7
From DNA to RNA

From DNA to Protein: How Cells Read the Genome

230
230 231 233 234 236 237 238 241 242 242 243 244 tRNA Molecules Match Amino Acids to Codons in mRNA Specific Enzymes Couple tRNAs to the Correct Amino Acid The RNA Message Is Decoded on Ribosomes The Ribosome Is a Ribozyme Codons in mRNA Signal Where to Start and to Stop Protein Synthesis Proteins Are Made on Polyribosomes Inhibitors of Procaryotic Protein Synthesis Are Used as Antibiotics Carefully Controlled Protein Breakdown Helps Regulate the Amount of Each Protein in a Cell There Are Many Steps Between DNA and Protein RNA a n d the Origins of Life Life Requires Autocatalysis RNA Can Both Store Information and Catalyze Chemical Reactions RNA Is Thought to Predate DNA in Evolution

229
245 248 248 251 253 254 255

Portions of DNA Sequence Are Transcribed into RNA Transcription Produces RNA Complementary to One Strand of DNA Several Types of RNA Are Produced in Cells Signals in DNA Tell RNA Polymerase Where to Start and Finish Eucaryotic RNAs Are Transcribed and Processed Simultaneously in the Nucleus Eucaryotic Genes Are Interrupted by Noncoding Sequences Introns Are Removed by RNA Splicing Mature Eucaryotic mRNAs Are Selectively Exported from the Nucleus mRNA Molecules Are Eventually Degraded by the Cell The Earliest Cells May Have Had Introns in Their Genes From RNA to Protein An mRNA Sequence Is Decoded in Sets of Three Nucleotides

256 257 258 259 259 261

Chapter 8

Control of Gene Expression

268/
268 268 270 Eucaryotic RNA Polymerase Requires General Transcription Factors Eucaryotic Gene Regulatory Proteins Control Gene Expression from a Distance Packing of Promoter DNA into Nucleosomes Can Affect Initiation of Transcription

267
276 278 279

An Overview of Gene Expression

The Different Cell Types of a Multicellular Organism Contain the Same DNA Different Cell Types Produce Different Sets of Proteins A Cell Can Change the Expression of Its Genes in Response to External Signals Gene Expression Can Be Regulated at Many of the Steps in the Pathway from DNA to RNA to Protein

The Molecular Mechanisms that Create Specialized Cell Types

Eucaryotic Genes Are Regulated by Combinations of Proteins The Expression of Different Genes Can Be Coordinated by a Single Protein Combinatorial Control Can Create Different Cell Types Stable Patterns of Gene Expression Can Be Transmitted to Daughter Cells The Formation of an Entire Organ Can Be Triggered by a Single Gene Regulatory Protein

280
281 281 285 286

270

How Transcriptional Switches Work

Transcription Is Controlled by Proteins Binding to Regulatory DNA Sequences Repressors Turn Genes Off, Activators Turn Them On An Activator and a Repressor Control the lac Operon Initiation of Eucaryotic Gene Transcription Is a Complex Process

271
271 273 275 275

288

Chapter 9:

How Genes and Genomes Evolve

293
295

293
304

Generating Genetic Variation

Five Main Types of Genetic Change Contribute to Evolution Genome Alterations Are Caused by Failures of the Normal Mechanisms for Copying and Maintaining DNA DNA Duplications Give Rise to Families of Related Genes Within a Single Cell The Evolution of the Globin Gene Family Shows How DNA Duplicatiops Contribute to the Evolution of Organisms Gene Duplication and Divergence Provide a Critical Source of Genetic Novelty for Evolving Organisms . New Genes Can Be Generated by Repeating the Same Exon Novel Genes Can Also Be Created by Exon Shuffling The Evolution of Genomes Has Been Accelerated by the Movement of Transposable Elements Genes Can Be Exchanged Between Organisms by Horizontal Gene Transfer

Reconstructing Life's Family Tree

Genetic Changes That Offer an Organism a Selective Advantage Are the Most Likely to Be Preserved The Genome Sequences of Two Species Differ in Proportion to the Length of Time That They Have Evolved Separately Humans and Chimpanzee Genomes Are Similar Organization as Well as Detailed Sequence Functionally Important Sequences Show Up as Islands of DNA Sequence Conservation Genome Comparisons Suggest That "Junk DNA" is Dispensable Sequence Conservation Allows Us to Trace Even the Most Distant Evolutionary Relationships

304

296 297

305 in 306 307 308 309

298

299 300 300

301 302

Examining the Human G e n o m e 311 The Nucleotide Sequence of the Human Genome Shows How Our Genes Are Arranged 311 Genetic Variation Within the Human Genome 313 Contributes to Our Individuality Comparing Our DNA with That of Related Organisms Helps Us to Interpret the Human 316 Genome The Human Genome Contains Copious Information Yet to Be Deciphered 317

Chapter 10

Manipulating Genes and Cells

DNA Cloning 324
325 325 326 327 328 329 331 333 336 336 338 340 DNA Ligase Joins DNA Fragments Together to Produce a Recombinant DNA Molecule Recombinant DNA Can Be Copied Inside Bacterial Cells Specialized Plasmid Vectors Are Used to Clone DNA Human Genes Are Isolated by DNA Cloning cDNA Libraries Represent the mRNA Produced by a Particular Tissue The Polymerase Chain Reaction Amplifies Selected DNA Sequences DNA Engineering Completely Novel DNA Molecules Can Be Constructed Rare Cellular Proteins Can Be Made in Large Amounts Using Cloned DNA Engineered Genes Can Reveal When and Where a Gene Is Expressed Mutant Organisms Best Reveal the Function of a Gene Animals Can Be Genetically Altered Transgenic Plants Are Important for Both Cell Biology and Agriculture

323
341
341 341 342 343 346

Isolating Cells and Growing Them in Culture

A Uniform Population of Cells Can Be Obtained from a Tissue Cells Can Be Grown in a Culture Dish Maintaining Eucaryotic Cells in Culture Poses Special Challenges How DNA Molecules Are Analyzed Restriction Nucleases Cut DNA Molecules at Specific Sites Gel Electrophoresis Separates DNA Fragments of Different Sizes The Nucleotide Sequence of DNA Fragments Can Be Determined Genome Sequences Are Searched to Identify Genes Nucleic A c i d Hybridization DNA Hybridization Facilitates the Diagnosis of Genetic Diseases Hybridization on DNA Microarrays Monitors the Expression of Thdusands of Genes at Once In Situ Hybridization Locates Nucleic Acid Sequences in Cells or on Chromosomes

347 352
352 352 353 355 356 359

Chapter 11
The Lipid Bilayer

Membrane Structure
366
367 370 371 373 373 374 375 A Polypeptide Chain Usually Crosses the Bilayer as an a Helix Membrane Proteins Can Be Solubilized in Detergents and Purified The Complete Structure Is Known for a Few Membrane Proteins The Plasma Membrane Is Reinforced by the Cell Cortex The Cell Surface Is Coated with Carbohydrate Cells Can Restrict the Movement of Membrane Proteins

365
376 377 378 380 381 383

Membrane Lipids Form Bilayers in Water The Lipid Bilayer Is a Two-dimensional Fluid The Fluidity of a Lipid Bilayer Depends on Its Composition The Lipid Bilayer Is Asymmetrical Lipid Asymmetry Is Generated Inside the Cell M e m b r a n e Proteins Membrane Proteins Associate with the Lipid Bilayer in Various Ways

Chapter 12

Membrane Transport
389 390 391 391 392 393 393 395 396 397 397 399 401 402

389
Ion Channels and the Membrane Potential
Ion Channels Are Ion-Selective and Gated Ion Channels Randomly Snap Between Open and Closed States Different Types of Stimuli Influence the Opening and Closing of Ion Channels Voltage-gated Ion Channels Respond to the Membrane Potential Membrane Potential Is Governed by Membrane Permeability to Specific Ions Ion Channels a n d Signaling in Nerve Cells

Principles of Membrane Transport

The Ion Concentrations Inside a Cell Are Very Different from Those Outside Lipid Bilayers Are Impermeable to Solutes and Ions Membrane Transport Proteins Fall into Two Classes: Carriers and Channels Solutes Cross Membranes by Passive or Active Transport Carrier Proteins a n d Their Functions Concentration Gradients and Electrical Forces Drive Passive Transport Active Transport Moves Solutes Against Their Electrochemical Gradients Animal Cells Use the Energy of ATP Hydrolysis to Pump Out Na + The Na + -K + Pump Is Driven by the Transient Addition of a Phosphate Group Animal Cells Use the Na + Gradient to Take Up Nutrients Actively The Na + -K + Pump Helps Maintain the Osmotic Balance of Animal Cells Intracellular C a 2 + Concentrations Are Kept Low by C a 2 + Pumps H + Gradients Are Used to Drive Membrane Transport in Plants, Fungi, and Bacteria

403
403 405 407 407 408 411

Action Potentials Provide for Rapid Long-Distance Communication 411 Action Potentials Are Usually Mediated by 412 Voltage-gated Na + Channels Voltage-gated C a 2 + Channels Convert Electrical Signals into Chemical Signals at 417 Nerve Terminals Transmitter-gated Channels in Target Cells Convert Chemical Signals Back into Electrical Signals 417 Neurons Receive Both Excitatory and Inhibitory Inputs 419 Transmitter-gated Ion Channels Are Major Targets for Psychoactive Drugs 419 Synoptic Connections Enable You to Think, Act, and Remember 420

Chapter 13

How Cells Obtain Energy from Food

428
428 430 431 434 435 439 Electron Transport Drives the Synthesis of the Majority of the ATP in Most Cells

427
441

The Breakdown of Sugars and Fats

Food Molecules Are Broken Down in Three Stages Glycolysis Is a Central ATP-producing Pathway Fermentations Allow ATP to Be Produced in the Absence of Oxygen Glycolysis illustrates How Enzymes Couple Oxidation to Energy Storage Sugars and Fats Are Both Degraded to Acetyl CoA in Mitochondria The Citric Acid Cycle Generates NADH by Oxidizing Acetyl Groups to CO2

Storing and Utilizing Food

Organisms Store Food Molecules in Special Reservoirs Chloroplasts and Mitochondria Collaborate in Plant Cells Many Biosynthetic Pathways Begin with Glycolysis or the Citric Acid Cycle Metabolism Is Organized and Regulated

444
444 446 447 448

Chapter 14

Energy Generation in Mitochondria and Chloroplasts

453 455 Electron Transfers Release Large Amounts of Energy Metals Tightly Bound to Proteins Form Versatile Electron Carriers Cytochrome Oxidase Catalyzes Oxygen Reduction The Mechanism of H+ Pumping Will Soon Be Understood in Atomic Detail Respiration Is Amazingly Efficient Chloroplasts a n d Photosynthesis Chloroplasts Resemble Mitochondria but Have an Extra Compartment Chloroplasts Capture Energy from Sunlight and Use It to Fix Carbon Excited Chlorophyll Molecules Funnel Energy into a Reaction Center Light Energy Drives the Synthesis of ATP and NADPH Carbon Fixation Is Catalyzed by Ribulose Bisphosphate Carboxylase Carbon Fixation in Chloroplasts Generates Sucrose and Starch

453
470 472 474 475 476 478 478 480 481 482 485 486

Cells Obtain Most of Their Energy by a Membrane-based Mechanism Mitochondria a n d Oxidative Phosphoryiation A Mitochondrion Contains an Outer Membrane, an Inner Membrane, and Two Internal Compartments High-Energy Electrons Are Generated via the Citric Acid Cycle A Chemiosmotic Process Converts Oxidation Energy into ATP Electrons Are Transferred Along a Chain of Proteins in the Inner Mitochondrial Membrane Electron Transport Generates a Proton Gradient Across the Membrane The Proton Gradient Drives ATP Synthesis Coupled Transport Across the Inner Mitochondrial Membrane Is Driven by the Electrochemical Proton Gradient Proton Gradients Produce Most of the Cell's ATP The Rapid Conversion of ADP to ATP in Mitochondria Maintains a High ATP/ADP Ratio in Cells Electron-Transport Chains a n d Proton Pumping Protons Are Readily Moved by the Transfer of Electrons The Redox Potential Is a Measure of Electron Affinities

455 457 458 459 462 464

466 466

468 468 468 469

The Origins of Chloroplasts a n d Mitochondria 487 Oxidative Phosphoryiation Gave Ancient Bacteria an Evolutionary Advantage 488 Photosynthetic Bacteria Made Even Fewer Demands on Their Environment 489 The Lifestyle of Methanococcus Suggests That Chemiosmotic Coupling Is an Ancient Process 490

Chapter 15

Intracellular Compartments and Transport

498 498 500 502 502 503 504 506 ^ 507 509 Vesicle Budding Is Driven by the Assembly of a Protein Coat The Specificity of Vesicle Docking Depends on SNAREs

497
513 515

Membrane-enclosed Organelles
Eucaryotic Cells Contain a Basic Set of Membrane-enclosed Organelles Membrane-enclosed Organelles Evolved in Different Ways

Secretory Pathways
Most Proteins Are Covalently Modified in the E R Exit from the ER Is Controlled to Ensure Protein Quality . Proteins Are Further Modified and Sorted in the Golgi Apparatus Secretory Proteins Are Released from the Cell by Exocytosis

516
516 517 518 519

Protein Sorting
Proteins Are Imported into Organelles by Three Mechanisms Signal Sequences Direct Proteins to the Correct Compartment Proteins Enter the Nucleus Through Nuclear Pores Proteins Unfold to Enter Mitochondria and Chloroplasts Proteins Enter the Endoplasmic Reticulum While Being Synthesized Soluble Proteins Are Released into the E Lumen R Start and Stop Signals Determine the Arrangement of a Transmembrane Protein in the Lipid Bilayer Vesicular Transport Transport Vesicles Carry Soluble Proteins and Membrane Between Compartments

510 512 512

Endocytic Pathways 523 Specialized Phagocytic Cells Ingest Large Particles 523 Fluid and Macromolecules Are Taken Up by Pinocytosis 525 Receptor-mediated Endocytosis Provides a Specific Route into Animal Cells 525 Endocytosed Macromolecules Are Sorted in Endosomes 526 Lysosomes Are the Principal Sites of Intracellular Digestion 527

Chapter 16

Cell Communication
533
534 536 538 540 541 542 544 545 546 546 548 549

533
The Cyclic AMP Pathway Can Activate Enzymes and Turn On Genes The Inositol Phospholipid Pathway Triggers a Rise in Intracellular C a 2 + A C a 2 + Signal Triggers Many Biological Processes Intracellular Signaling Cascades Can Achieve Astonishing Speed, Sensitivity, and Adaptability: A Look at Photoreceptors in the Eye 550 552 554

General Principles of Cell Signaling

Signals Can Act over Long or Short Range Each Cell Responds to a Limited Set of Signals Receptors Relay Signals via Intracellular Signaling Pathways Nitric Oxide Crosses the Plasma Membrane and Activates Intracellular Enzymes Directly Some Hormones Cross the Plasma, Membrane and Bind to Intracellular Receptors Cell-Surface Receptors Fall into Three Main Classes lon-channel-linked Receptors Convert Chemical Signals into Electrical Ones Many Intracellular Signaling Proteins Act as Molecular Switches G-protein-linked Receptors Stimulation of G-protein-linked Receptors Activates G-Protein Subunits Some G Proteins Regulate Ion Channels Some G Proteins Activate Membrane-bound Enzymes

555

Enzyme-linked Receptors 557 Activated Receptor Tyrosine Kinases Assemble a Complex of Intracellular Signaling Proteins 557 Receptor Tyrosine Kinases Activate the GTP-binding Protein Ras 559 Some Enzyme-linked Receptors Activate a Fast Track to the Nucleus 560 Protein Kinase Networks Integrate Information to Control Complex Cell Behaviors 565 Multicellularity and Cell Communication Evolved Independently in Plants and Animals 566

Chapter 17

Cytoskeleton
574
Actin and Tubulin Polymerize by Similar Mechanisms Many Proteins Bind to Actin and Modify Its Properties , . An Actin-rich Cortex Underlies the Plasma Membrane of Most Eucaryotic Cells Cell Crawling Depends on Actin Actin Associates with Myosin to Form Contractile Structures Extracellular Signals Control the Arrangement of Actin Filaments Muscle Contraction Muscle Contraction Depends on Bundles of Actin and Myosin During Muscle Contraction Actin Filaments Slide Against Myosin Filaments Muscle Contraction Is Triggered by a Sudden Rise in C a 2 + Muscle Cells Perform Highly Specialized Functions in the Body

573
593 594 594 595 598 599 600 600 601 603 605

Intermediate Filaments

Intermediate Filaments Are Strong and Ropelike 575 Intermediate Filaments Strengthen Cells Against Mechanical Stress 576 The Nuclear Envelope Is Supported by a Meshwork of Intermediate Filaments 578 Microtubules Microtubules Are Hollow Tubes with Structurally Distinct Ends . The Centrosome Is the Major Microtubuleorganizing Center in Animal Cells Growing Microtubules Show Dynamic Instability Microtubules Are Maintained by a Balance of Assembly and Disassembly Microtubules Organize the Interior of the Cell Motor Proteins Drive Intracellular Transport Organelles Move Along Microtubules Cilia and Flagella Contain Stable Microtubules Moved by Dynein Actin Filaments Actin Filaments Are Thin and Flexible 579 579 580 581 582 583 584 585 590 592 593

Chapter 18

Cell-Cycle Control and Cell Death

612
.613 614 615 616 Cells Can Dismantle Their Control System and Withdraw from the Cell Cycle Programmed Cell Death (Apoptosis) Apoptosis Is Mediated by an Intracellular Proteolytic Cascade The Death Program Is Regulated by the Bcl-2 Family of Intracellular Proteins Extracellular Control of Cell Numbers a n d Cell Size Animal Cells Require Extracellular Signals to Divide, Grow, and Survive Mitogens Stimulate Cell Division Extracellular Growth Factors Stimulate Cells to Grow Animal Cells Require Survival Factors to Avoid Apoptosis Some Extracellular Signal Proteins Inhibit Cell Growth, Division, or Survival

611
624 625 626 627 628 629 629 631 631 632

Overview of the Cell Cycle

The Eucaryotic Cell Cycle Is Divided into Four Phases A Central Control System Triggers the Major Processes of the Cell Cycle The Cell-Cycle Control System The Cell-Cycle Control System Depends on Cyclically Activated Protein Kinases Cyclin-dependent Protein Kinases Are Regulated by the Accumulation and Destruction of Cyclins The Activity of Cdks Is Also Regulated by Phosphoryiation and Dephosphorylation Different Cyclin-Cdk Complexes Trigger Different Steps in the Cell Cycle S-Cdk Initiates DNA Replication and Helps Block Rereplication Cdks Are Inactive Through Most of Gi The Cell-Cycle Control System Can Arrest the Cycle at Specific Checkpoints

617 617 620 621 622 622

Chapter 19

Cell Division
638
Chromosomes Line Up at the Spindle Equator at Metaphase Daughter Chromosomes Segregate x atAnaphase The Nuclear Envelope Re-forms at Telophase Some Organelles Fragment at Mitosis Cytokinesis The Mitotic Spindle Determines the Plane of Cytoplasmic Cleavage The Contractile Ring of Animal Cells Is Made of Actin and Myosin Cytokinesis in Plant Cells Involves New Cell-Wall Formation Gametes Are Formed by a Specialized Kind of Cell Division

637
648 649 651 651 652
V652

An Overview of M Phase
In Preparation for M Phase, DNA-binding Proteins Configure Replicated Chromosomes for Segregation The Cytoskeleton Carries Out Both Mitosis and Cytokinesis Centrosomes Duplicate To Help Form the Two Poles of the Mitotic Spindle M Phase Is Conventionally Divided into Six Stages Mitosis ' Microtubule Instability Facilitates the Formation of the Mitotic Spindle The Mitotic Spindle Starts to Assemble in Prophase Chromosomes Attach to the Mitotic Spindle at Prometaphase

638 639 640 640 641 641 644 645

653 654 655

Chapter 20
The Benefits of Sex

Genetics, Meiosis, and the Molecular Basis of Heredity

660
661 662 Each Gamete Carries a Single Allele for Each Character Mendel's Law of Segregation Applies to All Sexually Reproducing Organisms Alleles for Different Traits Segregate Independently The Behavior of Chromosomes During Meiosis Underlies Mendel's Laws of Inheritance The Frequency of Recombination Can Be Used to Order Genes on Chromosomes The Phenotype of the Heterozygote Reveals Whether an Allele is Dominant or Recessive Mutant Alleles Sometimes Confer a Selective Advantage

659
675 676 677 678 680 681 684 686 686 687 688

Sexual Reproduction Involves Both Diploid and Haploid Cells Sexual Reproduction Gives Organisms a Competitive Advantage

Meiosis
Haploid Cells Are Produced From Diploid Cells Through Meiosis Meiosis Involves a Special Process of Chromosome Pairing , Extensive Recombination Occurs Between Maternal and Paternal Chromosomes Chromosome Pairing and Recombination Ensure the Proper Segregation of Homologs The Second Meiotic Division Produces Haploid Daughter Cells The Haploid Cells Contain Extensively Reassorted Genetic Information Meiosis Is Not Flawless Fertilization Reconstitutes a Complete Genome

663
664 664 665 667 667 668 670 671

Mendel a n d the Laws of Inheritance 672 Mendel Chose to Study Traits That Are Inherited in a Discrete Fashion 673 Mendel Could Disprove the Alternative Theories of Inheritance ' 674 Mendel's Experiments Were the First to Reveal the Discrete feature of Heredity 674

Genetics as a n Experimental Tool The Classical Approach Begins with Random Mutagenesis Genetic Screens Identify Mutants Deficient in Cellular Processes A Complementation Test Reveals Whether Two Mutations Are in the Same Gene Human Genes Are Inherited in Haplotype Blocks, Which Can Aid in the Search for Mutations That Cause Disease Complex Traits Are Influenced by Multiple Genes Is Our Fate Encoded in Our DNA?

689 691 692

Chapter 21

Tissues and Cancer

698 698 702 703 704 705 706 706 709 709 711 Different Tissues Are Renewed at Different Rates Stem Cells Generate a Continuous Supply of Terminally Differentiated Cells Stem Cells Can Be Used to Repair Damaged Tissues Nuclear Transplantation Provides a Way to Generate Personalized ES Cells: the Strategy of Therapeutic Cloning

697
720 721 722

Extracellular Matrix a n d Connective Tissues Plant Cells Have Tough External Walls Cellulose Fibers Give the Plant Cell Wall Its Tensile Strength Animal Connective Tissues Consist Largely of Extracellular Matrix Collagen Provides Tensile Strength in Animal Connective Tissues " Cells Organize the Collagen That They Secrete Integrins Couple the Matrix Outside a Cell to the Cytoskeleton Inside It Gels of Polysaccharide and Protein Fill Spaces and Resist Compression Epithelial Sheets a n d Cell-Cell Junctions Epithelial Sheets Are Polarized and Rest on a Basal Lamina Tight Junctions Make an Epithelium Leak-proof and Separate Its Apical and Basal Surfaces Cytoskeleton-linked Junctions Bind Epithelial Cells Robustly to One Another and to the s Basal Lamina Gap Junctions Allow Ions and Small Molecules to Pass from Cell to Cell Tissue M a i n t e n a n c e a n d Renewal Tissues Are Organized Mixtures of Many Cell Types

725

Cancer
Cancer Cells Proliferate, Invade, and Metastasize . Epidemiology Identifies Preventable Causes of Cancer Cancers Develop by an Accumulation of Mutations Cancers Evolve Properties That Give Them a Competitive Advantage Many Diverse Types of Genes Are Critical for Cancer Colorectal Cancer Illustrates How Loss of a Gene Can Lead to Growth of a Tumor An Understanding of Cancer Cell Biology Opens the Way to New Treatments

726
726 727 728 729 731 732 736

712 715 717 718