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Karp's Cell Biology. Edition No. 8

  • ID: 4436195
  • Book
  • February 2018
  • 880 Pages
  • John Wiley and Sons Ltd
Karp’s Cell Biology, Global Edition continues to build on its strength at connecting key concepts to the experiments that reveal how we know what we know in the world of Cell Biology. This classic text explores core concepts in considerable depth, often adding experimental detail. It is written in an inviting style to assist students in handling the plethora of details encountered in the Cell Biology course. In this edition, two new co-authors take the helm and help to expand upon the hallmark strengths of the book, improving the student learning experience.
Note: Product cover images may vary from those shown

1 Introduction to Cell Biology 1

1.1 The Discovery of Cells 2

Microscopy 2

Cell Theory 3

1.2 Basic Properties of Cells 3

Cells are Highly Complex and Organized 3

Cells Possess a Genetic Program and the Means to Use It 5

Cells Are Capable of Producing More of Themselves 5

Cells Acquire and Utilize Energy 5

Cells Carry Out a Variety of Chemical Reactions 6

Cells Engage in Mechanical Activities 6

Cells are Able to Respond to Stimuli 6

Cells Are Capable of Self-Regulation 6

Cells Evolve 7

1.3 Two Fundamentally Different Classes of Cells 8

1.4 Types of Prokaryotic Cells 14

Domain Archaea and Domain Bacteria 14

Prokaryotic Diversity 14

1.5 Types of Eukaryotic Cells 15

Cell Differentiation 16

Model Organisms 16

1.6 The Sizes of Cells and Their Components 18

1.7 Viruses 19

Viroids 22

THE HUMAN PERSPECTIVE 23

The Prospect of Cell Replacement Therapy 23

EXPERIMENTAL PATHWAYS 27

The Origin of Eukaryotic Cells 27

2 The Structure and Functions of Biological Molecules 33

2.1 Covalent Bonds 34

Polar and Nonpolar Molecules 35

Ionization 36

2.2 Noncovalent Bonds 36

Ionic Bonds: Attractions between Charged Atoms 36

Hydrogen Bonds 36

Hydrophobic Interactions and van der Waals Forces 37

The Life-Supporting Properties of Water 38

2.3 Acids, Bases, and Buffers 39

2.4 The Nature of Biological Molecules 40

Functional Groups 41

A Classification of Biological Molecules by Function 41

2.5 Carbohydrates 42

The Structure of Simple Sugars 43

Stereoisomerism 43

Linking Sugars Together 44

Polysaccharides 45

2.6 Lipids 47

Fats 47

Steroids 48

Phospholipids 48

2.7 Building Blocks of Proteins 49

The Structures of Amino Acids 50

The Properties of the Side Chains 51

2.8 Primary and Secondary Structures of Proteins 54

Primary Structure 54

Secondary Structure 55

2.9 Tertiary Structure of Proteins 56

Myoglobin: The First Globular Protein Whose Tertiary Structure Was Determined 57

Tertiary Structure May Reveal Unexpected Similarities between Proteins 58

Protein Domains 58

Dynamic Changes within Proteins 59

2.10 Quaternary Structure of Proteins 60

The Structure of Hemoglobin 60

Protein–Protein Interactions 61

2.11 Protein Folding 61

Dynamics of Protein Folding 62

The Role of Molecular Chaperones 63

2.12 Proteomics and Interactomics 64

Proteomics 64

Interactomics 66

2.13 Protein Engineering 67

Production of Novel Proteins 67

Structure-Based Drug Design 68

2.14 Protein Adaptation and Evolution 69

2.15 Nucleic Acids 71

2.16 The Formation of Complex Macromolecular Structures 72

The Assembly of Tobacco Mosaic Virus Particles 73

The Assembly of Ribosomal Subunits 73

THE HUMAN PERSPECTIVE 73

I. Do Free Radicals Cause Aging? 73

II. Protein Misfolding Can Have Deadly Consequences 74

EXPERIMENTAL PATHWAYS 79

Chaperones - Helping Proteins Reach Their Proper Folded State 79

3 Bioenergetics, Enzymes, and Metabolism 87

3.1 Bioenergetics 88

The First Law of Thermodynamics 88

The Second Law of Thermodynamics 89

3.2 Free Energy 90

Free‐Energy Changes in Chemical Reactions 91

Free‐Energy Changes in Metabolic Reactions 92

3.3 Coupling Endergonic and Exergonic Reactions 94

3.4 Equilibrium versus Steady‐State Metabolism 94

3.5 Enzymes as Biological Catalysts 95

The Properties of Enzymes 96

Overcoming the Activation Energy Barrier 96

The Active Site 98

3.6 Mechanisms of Enzyme Catalysis 99

Substrate Orientation 100

Changing Substrate Reactivity 100

Inducing Strain in the Substrate 100

3.7 Enzyme Kinetics 103

The Michaelis‐Menten Model of Enzyme Kinetics 103

Enzyme Inhibitors 105

3.8 Metabolism 106

Oxidation and Reduction: A Matter of Electrons 107

The Capture and Utilization of Energy 108

3.9 Glycolysis and ATP Production 108

ATP Production in Glycolysis 109

Anaerobic Oxidation of Pyruvate: The Process of Fermentation 111

3.10 Reducing Power 112

3.11 Metabolic Regulation 113

Altering Enzyme Activity by Covalent Modification 113

Altering Enzyme Activity by Allosteric Modulation 113

3.12 Separating Catabolic and Anabolic Pathways 114

THE HUMAN PERSPECTIVE 115

I. The Growing Problem of Antibiotic Resistance 115

II. Caloric Restriction and Longevity 118

4 Genes, Chromosomes, and Genomes 123

4.1 The Concept of a Gene as a Unit of Inheritance 124

4.2 The Discovery of Chromosomes 125

4.3 Chromosomes: The Physical Carriers of the Genes 126

The Chromosome as a Linkage Group 127

4.4 Genetic Analysis in Drosophila 127

Crossing Over and Recombination 128

Mutagenesis and Giant Chromosomes 129

4.5 The Structure of DNA 129

The Watson‐Crick Proposal 132

The Importance of the Watson‐Crick Proposal 132

4.6 DNA Supercoiling 134

4.7 The Structure of the Genome 136

DNA Denaturation 137

DNA Renaturation 137

4.8 The Stability of the Genome 141

Whole‐Genome Duplication (Polyploidization) 141

Duplication and Modification of DNA Sequences 141

Evolution of Globin Genes 142

4.9 “Jumping Genes” and the Dynamic Nature of the Genome 143

Transposons 144

The Role of Mobile Genetic Elements in Genome Evolution 144

4.10 Sequencing Genomes: The Footprints of Biological Evolution 146

4.11 Comparative Genomics: “If It’s Conserved, It Must Be Important” 148

4.12 The Genetic Basis of “Being Human” 148

4.13 Genetic Variation within the Human Species Population 150

DNA Sequence Variation 150

Structural Variation 151

Copy Number Variation 152

THE HUMAN PERSPECTIVE 152

I. Diseases That Result from Expansion of Trinucleotide Repeats 152

II. Application of Genomic Analyses to Medicine 154

EXPERIMENTAL PATHWAYS 157

The Chemical Nature of the Gene 157

5 The Path to Gene Expression 165

5.1 The Relationship between Genes, Proteins, and RNAs 166

Evidence That DNA Is the Genetic Material 166

An Overview of the Flow of Information through the Cell 167

5.2 The Role of RNA Polymerases in Transcription 169

5.3 An Overview of Transcription in Both Prokaryotic and Eukaryotic Cells 171

Transcription in Bacteria 171

Transcription and RNA Processing in Eukaryotic Cells 172

5.4 Synthesis and Processing of Eukaryotic Ribosomal and Transfer RNAs 174

Synthesis and Processing of the rRNA Precursor 174

The Role of snoRNAs in the Processing of Pre‐rRNA 176

Synthesis and Processing of the 5S rRNA 176

Transfer RNAs 177

5.5 Synthesis and Structure of Eukaryotic Messenger RNAs 178

The Formation of Heterogeneous Nuclear RNA (hnRNA) 178

The Machinery for mRNA Transcription 178

The Structure of mRNAs 181

5.6 Split Genes: An Unexpected Finding 181

5.7 The Processing of Eukaryotic Messenger RNAs 184

5′ Caps and 3′ Poly(A) Tails 185

RNA Splicing: Removal of Introns from a Pre‐RNA 186

5.8 Evolutionary Implications of Split Genes and RNA Splicing 189

5.9 Creating New Ribozymes in the Laboratory 191

5.10 Small Regulatory RNAs and RNA Silencing Pathway 191

5.11 Small RNAs: miRNAs and piRNAs 193

miRNAs: A Class of Small RNAs that Regulate Gene Expression 193

piRNAs: A Class of Small RNAs that Function in Germ Cells 194

5.12 CRISPR and other Noncoding RNAs 195

CRISPR: Noncoding RNA in Bacteria 195

Other Noncoding RNAs 195

5.13 Encoding Genetic Information 196

The Properties of the Genetic Code 196

Identifying the Codons 197

5.14 Decoding the Codons: The Role of Transfer RNAs 198

The Structure of tRNAs 198

tRNA Charging 200

5.15 Translating Genetic Information: Initiation 201

Initiation of Translation in Prokaryotes 202

Initiation of Translation in Eukaryotes 203

The Role of the Ribosome 203

5.16 Translating Genetic Information: Elongation and Termination 205

Elongation Step 1: Aminoacyl‐tRNA Selection 205

Elongation Step 2: Peptide Bond Formation 205

Elongation Step 3: Translocation 205

Elongation Step 4: Releasing the Deacylated tRNA 206

Termination 207

5.17 mRNA Surveillance and Quality Control 208

5.18 Polyribosomes 209

THE HUMAN PERSPECTIVE 210

Clinical Applications of RNA Interference 210

EXPERIMENTAL PATHWAYS 212

The Role of RNA as a Catalyst 212

6 Controlling Gene Expression 220

6.1 Control of Gene Expression in Bacteria 221

Organization of Bacterial Genomes 221

The Bacterial Operon 221

Riboswitches 224

6.2 Control of Gene Expression in Eukaryotes: Structure and Function of the Cell Nucleus 225

The Nuclear Pore Complex and Its Role in Nucleocytoplasmic Trafficking 227

RNA Transport 230

6.3 Chromosomes and Chromatin 230

Nucleosomes: The Lowest Level of Chromosome Organization 230

Higher Levels of Chromatin Structure 232

6.4 Heterochromatin and Euchromatin 234

X Chromosome Inactivation 234

The Histone Code and Formation of Heterochromatin 235

6.5 The Structure of a Mitotic Chromosome 238

Telomeres 240

Centromeres 243

6.6 Epigenetics: There’s More to Inheritance than DNA 243

6.7 The Nucleus as an Organized Organelle 244

6.8 An Overview of Gene Regulation in Eukaryotes 247

6.9 Transcriptional Control 248

DNA Microarrays 249

RNA Sequencing 251

6.10 The Role of Transcription Factors in Regulating Gene Expression 252

The Role of Transcription Factors in Determining a Cell’s Phenotype 252

6.11 The Structure of Transcription Factors 253

Transcription Factor Motifs 253

6.12 DNA Sites Involved in Regulating Transcription 256

6.13 The Glucocorticoid Receptor: An Example of Transcriptional Activation 258

6.14 Transcriptional Activation: The Role of Enhancers, Promoters, and Coactivators 259

Coactivators That Interact with the Basal Transcription Machinery 260

Coactivators That Alter Chromatin Structure 260

6.15 Transcriptional Activation from Paused Polymerases 263

6.16 Transcriptional Repression 264

DNA Methylation 264

Genomic Imprinting 265

Long Noncoding RNAs (lncRNAs) as Transcriptional Repressors 266

6.17 RNA Processing Control 267

6.18 Translational Control 269

Initiation of Translation 269

Cytoplasmic Localization of mRNAs 270

The Control of mRNA Stability 271

6.19 The Role of MicroRNAs in Translational Control 273

6.20 Posttranslational Control: Determining Protein Stability 274

THE HUMAN PERSPECTIVE 275

Chromosomal Aberrations and Human Disorders 275

7 DNA Replication and Repair 282

7.1 DNA Replication 283

7.2 DNA Replication in Bacterial Cells 286

Replication Forks and Bidirectional Replication 287

Unwinding the Duplex and Separating the Strands 287

The Properties of DNA Polymerases 288

Semidiscontinuous Replication 289

7.3 The Machinery Operating at the Replication Fork 291

7.4 The Structure and Functions of DNA Polymerases 293

Exonuclease Activities of DNA Polymerases 293

Ensuring High Fidelity during DNA Replication 294

7.5 Replication in Viruses 296

7.6 DNA Replication in Eukaryotic Cells 296

Initiation of Replication in Eukaryotic Cells 297

Restricting Replication to Once Per Cell Cycle 297

The Eukaryotic Replication Fork 298

Replication and Nuclear Structure 300

7.7 Chromatin Structure and Replication 300

7.8 DNA Repair 302

Nucleotide Excision Repair 302

Base Excision Repair 303

Mismatch Repair 304

Double‐Strand Breakage Repair 304

7.9 Between Replication and Repair 305

THE HUMAN PERSPECTIVE 306

Consequences of DNA Repair Deficiencies 306

8 Cellular Membrane 311

8.1 Introduction to the Plasma Membrane 312

An Overview of Membrane Functions 312

A Brief History of Studies on Plasma Membrane Structure 313

8.2 The Chemical Composition of Membranes 315

Membrane Lipids 316

The Nature and Importance of the Lipid Bilayer 317

The Asymmetry of Membrane Lipids 319

8.3 Membrane Carbohydrates 319

8.4 The Structure and Functions of Membrane Proteins 320

Integral Membrane Proteins 321

Peripheral Membrane Proteins 322

Lipid‐Anchored Membrane Proteins 322

8.5 Studying the Structure and Properties of Integral Membrane Proteins 323

Identifying Transmembrane Domains 324

Experimental Approaches to Identifying Conformational Changes within an Integral Membrane Protein 325

8.6 Membrane Lipids and Membrane Fluidity 327

The Importance of Membrane Fluidity 328

Maintaining Membrane Fluidity 328

Lipid Rafts 329

8.7 The Dynamic Nature of the Plasma Membrane 329

The Diffusion of Membrane Proteins after Cell Fusion 330

Restrictions on Protein and Lipid Mobility 331

8.8 The Red Blood Cell: An Example of Plasma Membrane Structure 334

Integral Proteins of the Erythrocyte Membrane 334

The Erythrocyte Membrane Skeleton 336

8.9 The Movement of Substances across Cell Membranes 336

The Energetics of Solute Movement 336

Formation of an Electrochemical Gradient 337

8.10 Diffusion through the Lipid Bilayer 338

Diffusion of Substances through Membranes 338

The Diffusion of Water through Membranes 338

8.11 The Diffusion of Ions through Membranes 340

8.12 Facilitated Diffusion 345

8.13 Active Transport 346

Primary Active Transport: Coupling Transport to ATP Hydrolysis 346

Other Primary Ion Transport Systems 347

Using Light Energy to Actively Transport Ions 348

Secondary Active Transport (or Cotransport): Coupling Transport to Existing Ion Gradients 348

8.14 Membrane Potentials 350

The Resting Potential 350

The Action Potential 352

8.15 Propagation of Action Potentials as an Impulse 353

8.16 Neurotransmission: Jumping the Synaptic Cleft 354

Actions of Drugs on Synapses 356

Synaptic Plasticity 357

THE HUMAN PERSPECTIVE 357

Defects in Ion Channels and Transporters as a Cause of Inherited Disease 357

EXPERIMENTAL PATHWAYS 359

The Acetylcholine Receptor 359

9 Mitochondrion and Aerobic Respiration 368

9.1 Mitochondrial Structure and Function 369

Mitochondrial Membranes 370

The Mitochondrial Matrix 372

9.2 Oxidative Metabolism in the Mitochondrion 372

The Tricarboxylic Acid (TCA) Cycle 373

The Importance of Reduced Coenzymes in the Formation of ATP 375

9.3 The Role of Mitochondria in the Formation of ATP 377

Oxidation–Reduction Potentials 377

Electron Transport 379

Types of Electron Carriers 379

9.4 Electron‐Transport Complexes 381

Complex I (NADH dehydrogenase) 383

Complex II (succinate dehydrogenase) 384

Complex III (cytochrome bc1) 384

Complex IV (cytochrome c oxidase) 384

9.5 Translocation of Protons and the Establishment of a Proton‐ Motive Force 385

9.6 The Machinery for ATP Formation 386

The Structure of ATP Synthase 387

9.7 The Binding Change Mechanism of ATP Formation 388

Components of the Binding Change Hypothesis 388

Evidence to Support the Binding Change Mechanism and Rotary Catalysis 389

9.8 Using the Proton Gradient 391

The Role of the Fo Portion of ATP Synthase in ATP Synthesis 391

Other Roles for the Proton‐Motive Force in Addition to ATP Synthesis 392

9.9 Peroxisomes 392

THE HUMAN PERSPECTIVE 394

I. The Role of Anaerobic and Aerobic Metabolism in Exercise 394

II. Diseases that Result from Abnormal Mitochondrial or Peroxisomal Function 395

10 Chloroplast and Photosynthesis 401

10.1 The Origin of Photosynthesis 402

10.2 Chloroplast Structure and Function 403

10.3 An Overview of Photosynthetic Metabolism 404

10.4 The Absorption of Light 405

Photosynthetic Pigments 406

10.5 Photosynthetic Units and Reaction Centers 407

Oxygen Formation: Coordinating the Action of Two Different Photosynthetic Systems 408

10.6 The Operations of Photosystem II and Photosystem I 409

PSII Operations: Obtaining Electrons by Splitting Water 409

PSI Operations: The Production of NADPH 412

10.7 An Overview of Photosynthetic Electron Transport 413

Killing Weeds by Inhibiting Electron Transport 414

10.8 Photophosphorylation 415

Noncyclic Versus Cyclic Photophosphorylation 415

10.9 Carbon Dioxide Fixation and the Carbohydrate Synthesis 415

Carbohydrate Synthesis in C3 Plants 416

Redox Control 416

Photorespiration 417

Peroxisomes and Photorespiration 418

10.10 Carbohydrate Synthesis in C4 and CAM Plants 420

THE HUMAN PERSPECTIVE 421

Global Warming and Carbon Sequestration 421

11 The Extracellular Matrix and Cell Interactions 426

11.1 Overview of Extracellular Interactions 427

11.2 The Extracellular Space 428

The Extracellular Matrix 428

11.3 Components of the Extracellular Matrix 430

Collagen 430

Proteoglycans 432

Fibronectin 433

Laminin 433

11.4 Dynamic Properties of the Extracellular Matrix 435

11.5 Interactions of Cells with Extracellular Materials 436

Integrins 436

11.6 Anchoring Cells to Their Substratum 438

Focal Adhesions 438

Hemidesmosomes 440

11.7 Interactions of Cells with Other Cells 441

Selectins 441

The Immunoglobulin Superfamily 442

Cadherins 443

11.8 Adherens Junctions and Desmosomes: Anchoring Cells to Other Cells 445

11.9 The Role of Cell‐Adhesion Receptors in Transmembrane Signaling 447

11.10 Tight Junctions: Sealing the Extracellular Space 447

11.11 Gap Junctions and Plasmodesmata: Mediating Intercellular Communication 449

Gap Junctions 449

Plasmodesmata 451

11.12 Cell Walls 453

THE HUMAN PERSPECTIVE 455

The Role of Cell Adhesion in Inflammation and Metastasis 455

EXPERIMENTAL PATHWAYS 457

The Role of Gap Junctions in Intercellular Communication 457

12 Cellular Organelles and Membrane Trafficking 463

12.1 An Overview of the Endomembrane System 464

12.2 A Few Approaches to the Study of Endomembranes 466

Insights Gained from Autoradiography 466

Insights Gained from the Use of the Green Fluorescent Protein 467

Insights Gained from the Analysis of Subcellular Fractions 468

Insights Gained from the Use of Cell‐Free Systems 469

Insights Gained from the Study of Mutant Phenotypes 470

12.3 The Endoplasmic Reticulum 472

The Smooth Endoplasmic Reticulum 473

The Rough Endoplasmic Reticulum 473

12.4 Functions of the Rough Endoplasmic Reticulum 473

Synthesis of Proteins on Membrane‐Bound versus Free Ribosomes 473

Synthesis of Secretory, Lysosomal, or Plant Vacuolar Proteins 475

Processing of Newly Synthesized Proteins in the Endoplasmic Reticulum 476

Synthesis of Integral Membrane Proteins on ER‐Bound Ribosomes 476

12.5 Membrane Biosynthesis in the Endoplasmic Reticulum 477

12.6 Glycosylation in the Rough Endoplasmic Reticulum 479

12.7 Mechanisms That Ensure the Destruction of Misfolded Proteins 481

12.8 ER to Golgi Vesicular Transport 482

12.9 The Golgi Complex 482

Glycosylation in the Golgi Complex 484

The Movement of Materials through the Golgi Complex 485

12.10 Types of Vesicle Transport and Their Functions 487

COPII‐Coated Vesicles: Transporting Cargo from the ER to the Golgi Complex 488

COPI‐Coated Vesicles: Transporting Escaped Proteins Back to the ER 489

12.11 Beyond the Golgi Complex: Sorting Proteins at the TGN 491

Sorting and Transport of Lysosomal Enzymes 491

Sorting and Transport of Nonlysosomal Proteins 493

12.12 Targeting Vesicles to a Particular Compartment 493

12.13 Exocytosis 496

12.14 Lysosomes 496

12.15 Plant Cell Vacuoles 498

12.16 Endocytosis 498

Receptor‐Mediated Endocytosis and the Role of Coated Pits 499

The Role of Phosphoinositides in the Regulation of Coated Vesicles 501

12.17 The Endocytic Pathway 502

12.18 Phagocytosis 505

12.19 Posttranslational Uptake of Proteins by Peroxisomes, Mitochondria, and Chloroplasts 505

Uptake of Proteins into Peroxisomes 506

Uptake of Proteins into Mitochondria 506

Uptake of Proteins into Chloroplasts 507

THE HUMAN PERSPECTIVE 508

Disorders Resulting from Defects in Lysosomal Function 508

EXPERIMENTAL PATHWAYS 510

Receptor‐Mediated Endocytosis 510

13 The Cytoskeleton 517

13.1 Overview of the Major Functions of the Cytoskeleton 518

13.2 Microtubules: Structure and Function 520

Structure and Composition of Microtubules 520

Microtubule‐Associated Proteins 521

Microtubules as Structural Supports and Organizers 521

Microtubules as Agents of Intracellular Motility 522

13.3 Motor Proteins: Kinesins and Dyneins 524

Motor Proteins Traverse the Microtubular Cytoskeleton 524

Kinesins 524

Cytoplasmic Dynein 526

13.4 Microtubule‐Organizing Centers (MTOCs) 527

Centrosomes 528

Basal Bodies and Other MTOCs 530

Microtubule Nucleation 530

13.5 Microtubule Dynamics 530

The Dynamic Properties of Microtubules 530

The Underlying Basis of Microtubule Dynamics 532

13.6 Cilia and Flagella: Structure and Function 534

Structure of Cilia and Flagella 535

Growth by Intraflagellar Transport 537

The Mechanism of Ciliary and Flagellar Locomotion 539

13.7 Intermediate Filaments 541

Intermediate Filament Assembly and Disassembly 541

Types and Functions of Intermediate Filaments 543

13.8 Microfilaments 544

Microfilament Structure 544

Microfilament Assembly and Disassembly 545

13.9 Myosin: The Molecular Motor of Actin Filaments 547

Conventional (Type II) Myosins 547

Unconventional Myosins 548

13.10 Muscle Contractility 552

Organization of Sarcomeres 552

The Sliding Filament Model of Muscle Contraction 553

13.11 Nonmuscle Motility 557

Actin-Binding Proteins 558

13.12 Cellular Motility 560

13.13 Actin‐Dependent Processes During Development 564

Axonal Outgrowth 564

13.14 The Bacterial Cytoskeleton 567

THE HUMAN PERSPECTIVE 568

The Role of Cilia in Development and Disease 568

EXPERIMENTAL PATHWAYS 569

I. The Step Size of Kinesin 569

II. Studying Actin‐Based Motility without Cells 571

14 Cell Division 578

14.1 The Cell Cycle 579

Phases of the Cell Cycle 579

Cell Cycles in Vivo 580

14.2 Regulation of the Cell Cycle 581

14.3 Control of the Cell Cycle: The Role of Protein Kinases 582

Cyclin Binding 583

Cdk Phosphorylation/Dephosphorylation 583

Cdk Inhibitors 584

Controlled Proteolysis 584

Subcellular Localization 584

14.4 Control of the Cell Cycle: Checkpoints, Cdk Inhibitors, and Cellular Responses 586

14.5 M Phase: Mitosis and Cytokinesis 588

14.6 Prophase 588

Formation of the Mitotic Chromosome 588

Centromeres and Kinetochores 590

Formation of the Mitotic Spindle 591

The Dissolution of the Nuclear Envelope and Partitioning of Cytoplasmic Organelles 594

14.7 Prometaphase 594

14.8 Metaphase 596

14.9 Anaphase 598

The Role of Proteolysis in Progression through Mitosis 598

The Events of Anaphase 600

Forces Required for Chromosome Movements at Anaphase 601

The Spindle Assembly Checkpoint 602

14.10 Telophase and Cytokinesis 603

Motor Proteins Required for Mitotic Movements 603

Cytokinesis 603

Cytokinesis in Plant Cells: Formation of the Cell Plate 607

14.11 Meiosis 608

14.12 The Stages of Meiosis 610

14.13 Genetic Recombination during Meiosis 613

THE HUMAN PERSPECTIVE 615

Meiotic Nondisjunction and Its Consequences 615

EXPERIMENTAL PATHWAYS 616

The Discovery and Characterization of MPF 616

15 Cell Signaling Pathways 624

15.1 The Basic Elements of Cell Signaling Systems 625

15.2 A Survey of Extracellular Messengers and their Receptors 628

15.3 Signal Transduction by G Protein‐Coupled Receptors 629

Receptors 629

G Proteins 630

Termination of the Response 631

Bacterial Toxins 632

15.4 Second Messengers 632

The Discovery of Cyclic AMP 633

Phosphatidylinositol‐Derived Second Messengers 633

Phospholipase C 635

15.5 The Specificity of G Protein‐Coupled Responses 636

15.6 Regulation of Blood Glucose Levels 636

Glucose Mobilization: An Example of a Response Induced by cAMP 637

Signal Amplification 638

Other Aspects of cAMP Signal Transduction Pathways 638

15.7 The Role of GPCRs in Sensory Perception 640

15.8 Protein‐Tyrosine Phosphorylation as a Mechanism for Signal Transduction 641

Receptor Dimerization 641

Protein Kinase Activation 643

Phosphotyrosine‐Dependent Protein–Protein Interactions 643

Activation of Downstream Signaling Pathways 643

Ending the Response 645

15.9 The Ras‐MAP Kinase Pathway 645

Accessory Proteins 645

Adapting the MAP Kinase to Transmit Different Types of Information 647

15.10 Signaling by the Insulin Receptor 648

The Insulin Receptor Is a Protein‐Tyrosine Kinase 648

Insulin Receptor Substrates 1 and 2 649

Glucose Transport 650

Diabetes Mellitus 650

15.11 Signaling Pathways in Plants 651

15.12 The Role of Calcium as an Intracellular Messenger 651

IP3 and Voltage‐Gated Ca2+ Channels 651

Visualizing Cytoplasmic Ca2+ Concentration in Living Cells 651

Ca2+‐Binding Proteins 654

Regulating Calcium Concentrations in Plant Cells 654

15.13 Convergence, Divergence, and Cross‐Talk among Different Signaling Pathways 655

15.14 The Role of NO as an Intercellular Messenger 657

NO as an Activator of Guanylyl Cyclase 658

Inhibiting Phosphodiesterase 658

15.15 Apoptosis (Programmed Cell Death) 659

The Extrinsic Pathway of Apoptosis 660

The Intrinsic Pathway of Apoptosis 661

Necroptosis 662

Signaling Cell Survival 663

THE HUMAN PERSPECTIVE 663

Disorders Associated with G Protein‐Coupled Receptors 663

EXPERIMENTAL PATHWAYS 665

The Discovery and Characterization of GTP‐Binding Proteins 665

16 Cancer 673

16.1 Basic Properties of a Cancer Cell 674

16.2 The Causes of Cancer 677

16.3 The Genetics of Cancer 678

16.4 An Overview of Tumor‐Suppressor Genes and Oncogenes 680

16.5 Tumor‐Suppressor Genes: The RB Gene 681

16.6 Tumor‐Suppressor Genes: The TP53 Gene 684

The Role of p53: Guardian of the Genome 684

The Role of p53 in Promoting Senescence 686

16.7 Other Tumor‐Suppressor Genes 687

16.8 Oncogenes 688

Oncogenes That Encode Growth Factors or Their Receptors 688

Oncogenes That Encode Cytoplasmic Protein Kinases 689

Oncogenes That Encode Transcription Factors 689

Oncogenes That Encode Proteins That Affect the Epigenetic State of Chromatin 689

Oncogenes That Encode Metabolic Enzymes 690

Oncogenes That Encode Products That Affect Apoptosis 690

16.9 The Mutator Phenotype: Mutant Genes Involved in DNA Repair 691

16.10 MicroRNAs: A New Player in the Genetics of Cancer 691

16.11 The Cancer Genome 691

16.12 Gene‐Expression Analysis 694

16.13 Strategies for Combating Cancer 696

16.14 Immunotherapy 696

16.15 Inhibiting the Activity of Cancer‐Promoting Proteins 698

16.16 The Concept of a Cancer Stem Cell 701

16.17 Inhibiting the Formation of New Blood Vessels (Angiogenesis) 701

EXPERIMENTAL PATHWAYS 702

The Discovery of Oncogenes 702

17 Immunity 709

17.1 An Overview of the Immune Response 710

Innate Immune Responses 711

Adaptive Immune Responses 713

17.2 The Clonal Selection Theory as It Applies to B Cells 714

17.3 Vaccination 715

17.4 T Lymphocytes: Activation and Mechanism of Action 717

17.5 The Modular Structure of Antibodies 720

17.6 DNA Rearrangements That Produce Genes Encoding B‐ and T‐Cell Antigen Receptors 723

17.7 Membrane‐Bound Antigen Receptor Complexes 725

17.8 The Major Histocompatibility Complex 726

17.9 Distinguishing Self from Nonself 730

17.10 Lymphocytes Are Activated by Cell‐Surface Signals 731

Activation of Helper T Cells by Professional APCs 731

Activation of B Cells by TH Cells 732

17.11 Signal Transduction Pathways in Lymphocyte Activation 732

THE HUMAN PERSPECTIVE 733

Autoimmune Diseases 733

EXPERIMENTAL PATHWAYS 736

The Role of the Major Histocompatibility Complex in Antigen Presentation 736

18 Techniques in Cell and Molecular Biology 742

18.1 The Light Microscope 743

Resolution 744

Visibility 745

18.2 Bright‐Field and Phase‐Contrast Microscopy 745

Bright‐Field Light Microscopy 745

Phase‐Contrast Microscopy 746

18.3 Fluorescence Microscopy (and Related Fluorescence‐Based Techniques) 746

Laser Scanning Confocal Microscopy 749

Super‐Resolution Fluorescence Microscopy 750

Light Sheet Fluorescence Microscopy 751

18.4 Transmission Electron Microscopy 752

18.5 Specimen Preparation for Electron Microscopy 753

Cryofixation and the Use of Frozen Specimens 754

Negative Staining 755

Shadow Casting 755

Freeze‐Fracture Replication and Freeze Etching 756

18.6 Scanning Electron Microscopy 757

18.7 Atomic Force Microscopy 758

18.8 The Use of Radioisotopes 759

18.9 Cell Culture 760

18.10 The Fractionation of a Cell’s Contents by Differential Centrifugation 762

18.11 Purification and Characterization of Proteins by Liquid Column Chromatography 762

Ion‐Exchange Chromatography 763

Gel Filtration Chromatography 763

Affinity Chromatography 764

18.12 Determining Protein–Protein Interactions 764

18.13 Characterization of Proteins by

Polyacrylamide Gel Electrophoresis 766

SDS–PAGE 767

Two‐Dimensional Gel Electrophoresis 767

18.14 Characterization of Proteins by Spectrometry 767

18.15 Characterization of Proteins by Mass Spectrometry 767

18.16 Determining the Structure of Proteins and Multisubunit Complexes 768

18.17 Fractionation of Nucleic Acids 770

Separation of DNAs by Gel Electrophoresis 770

Separation of Nucleic Acids by Ultracentrifugation 771

18.18 Nucleic Acid Hybridization 773

18.19 Chemical Synthesis of DNA 774

18.20 Recombinant DNA Technology 774

Restriction Endonucleases 774

Formation of Recombinant DNAs 775

DNA Cloning 776

18.21 Enzymatic Amplification of DNA by PCR 778

Process of PCR 778

Applications of PCR 778

18.22 DNA Sequencing 780

18.23 DNA Libraries 782

Genomic Libraries 782

cDNA Libraries 783

18.24 DNA Transfer into Eukaryotic Cells and Mammalian Embryos 783

Transgenic Animals 785

Transgenic Plants 785

18.25 Gene Editing and Silencing 786

In Vitro Mutagenesis 786

Knockout Mice 787

RNA Interference 788

Genome Editing Using Engineered Nucleases 789

18.26 The Use of Antibodies 789

Glossary G-1

Additional Reading A-1

Index I-1

Note: Product cover images may vary from those shown
Gerald Karp Formerly of the University of Florida, Gainesville.

Janet Iwasa University of Utah.

Wallace Marshall University of California, San Francisco.
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