The Cell, A Molecular Approach, 4th Edition

The fourth edition of “The Cell” has been thoroughly updated to reflect major advances in the field, including the role of microRNAs in the regulation of gene expression, advances in stem cell biology, as well as Oncogenes and the rational design of new anticancer drugs. While retaining the overall structure and pedagogy that made previous editions so successful, the fourth edition now includes additional chapters on Programmed Cell death and the Maintenance of Adult Tissues. There is also significant new material on topics like Signalling Networks, Cell-Matrix Interactions and Bioinformations to keep “The Cell” fresh, vibrant and perpetually appealing to students.

Table of Contents

Preface xiv
Organization and Features of The Cell xvi
Media and Supplements to Accompany The Cell xviii
PART Introduction
1
An Overview of Cells
and Cell Research 3
Tbe Origin and Evolution of Cells 4
The First Cell 4
The Evolution of Metabolism 7
Present-Day Prokaryotes 8
Eukaryotic Cells 9
The Origin of Eukaryotes 10
The Development of Multicellular
Organisms 12
Cells as Experimental Models 16
E. coli 16
Yeasts 17
Caenorhabditis elegans 17
Drosophila melanogaster 18
Arabidopsis thaliana 19
Vertebrates 19
Tools of Cell Biology 11
Light Microscopy 21
Electron Microscopy 27
Subcellular Fractionation 30
Growth of Animal Cells in Culture 33
Culture of Plant Cells 36
Viruses 36
• KEY EXPERIMENT Animal Cell
Culture 35
• MOLECULAR MEDICINE Viruses
and Cancer 37
Summary and Key Terms 39
Questions 41
References and Further Reading 41
2
The Composition
of Cells 43
The Molecules of Cells 43
Carbohydrates 44
Lipids 46
Nucleic Acids 50
Proteins 52
Cell Membranes 58
Membrane Lipids 60
Membrane Proteins 61
Transport across Cell Membranes 63
Proteomics: Large-Scale Analysis
of Cell Proteins 65
Identification of Cell Proteins 65
Global Analysis of Protein Localization 68
Protein Interactions 69
• KEY EXPERIMENT The Folding of
Polypeptide Chains 54
• KEY EXPERIMENT The Structure
of Cell Membranes 59
Summary and Key Terms 70
Questions 71
References and Further Reading 71
3
Cell Metabolism 73
The Central Role of Enzymes as
Biological Catalysts 73
The Catalytic Activity of Enzymes 73
Mechanisms of Enzymatic Catalysis 74
Coenzymes 78
Regulation of Enzyme Activity 79
Metabolic Energy 81
Free Energy and ATP 81
The Generation of ATP from Glucose 84
The Derivation of Energy from Other
Organic Molecules 89
Photosynthesis 90

11te Biosynthesis of Cell
Constituents 91
Carbohydrat~:; 92
Lipids 93
Proteins 94
Nucleic Acids 97
• KEY EXPERIMENT Antimetabo/ites
and Chemotherapy 98
• MOLECULAR MEDICINE
Phenylketonuria 96
Summary and Key Terms 100
Questions 101
References and Further Reading 101
4
Fundamentals of
Molecular Biology 10l
Heredity, Genes, and DNA 103
Genes and Chromosomes 104
Genes and Enzymes 107
Identification of DNA as the Genetic
Material 107
The Structure of DNA 108
Replication of DNA 110
Expression of Genetic
Information 111
Colinearity of Genes and Proteins 111
The Role of Messenger RNA 112
The Genetic Code 113
RNA Viruses and Reverse Transcription
115
Recombinant DNA 118
Restriction Endonucleases 118
Generation of Recombinant DNA
Molecules 121
Vectors for Recombinant DNA 122
DNA Sequencing 125
Expression of Cloned Genes 126
Detedion of Nucleic Acids and
Proteins 119
Amplification of DNA by the Polymerase
Chain Reaction 129
Nucleic Acid Hybridization 131
Antibodies as Probes for Proteins 134
Gene Fundion in Eukaryotes 137
Genetic Analysis in Yeasts 137
Gene Transfer in Plants and Animals 139
Mutagenesis of Cloned DNAs 142
lntroducing Mutations into Cellular
Genes 142
lnterfering with Cellular Gene
Expression 145
• KEY EXPERIMENT The DNA Provirus
Hypothesis 116
• MOLECULAR MEDICINE HIV and
AIDS 120
Summary and Key Terms 147
Questions 149
References and Further Reading 150
PART The Flow of Genetic Information
5
The Organization and
Sequences of Cellular
Genomes 155
11te Complexity of Eukaryotic
Genomes 155
Introns and Exons 157
Repetitive DNA Sequences 161
Gene Duplication and Pseudogenes 164
The Composition of Higher Eukaryotic
Genomes 165
Chromosomes and Chromatin 166
Chromatin 166
Centromeres 171
Telomeres 175
11te Sequences of Complete
Genomes 176
Prokaryotic Genomes 177
The Yeast Genome 178
The Genomes of Caenorhabditis elegans
and Drosophila melanogaster 180
Plant Genomes 183
The Human Genome 185
The Genomes of Other Vertebrates 190
Bioinformatics and Systems
Biology 191
Systematic Screens of Gene Function 193
Regulation of Gene Expression 194
Variation among Individuals and
Genomic Medicine 195
• KEY EXPERIMENT The Discovery
of lntrons 158
• KEY EXPERIMENT The Human
Genome 188
Summary and Key Terms 196
Questions 198
References and Further Reading 199

6
Replication,
Maintenance, and
Rearrangements of
Genomic DNA 201
DNA Replication 101
DNA Polymerases 202
The Replication Fork 202
The Fidelity of Replication 209
Origins and the Initiation of
Replication 211
Telomeres and Telomerase: Maintaining
the Ends of Chromosomes 214
DNA Repair 116
Direct Reversal of DNA Damage 216
Excision Repair 219
Translesion DNA Synthesis 223
Recombinational Repair 225
Recombination between Homologous
DNA Sequences 117
Models of Homologous
Recombination 228
Enzymes Involved in Homologous
Recombination 229
DNA Rearrangements 133
Site-Specific Recombination 233
Transposition via DNA Intermediates 239
Transposition via RNA Intermediates 242
Gene Amplification 247
• KEY EXPERIMENT Rearrangement of
Immunoglobulin Genes 240
il MOLECULAR MEDICINE Colon
Cancer and DNA Repair 224
Summary and Key Terms 249
Questions 250
References and Further Reading 251
7
RNA Synthesis and
Processing 253
Transcription in Prokaryotes 154
RNA Polymerase and Transcription 254
Repressors and Negative Control of
Transcription 258
Positive Control of Transcription 261
Eukaryotic RNA Polymerases and
General Transcription Factors 161
Eukaryotic RNA Polymerases 262
General Transcription Factors and
Initiation of Transcription by RNA
Polymerase II 262
Transcription by RNA Polymerases I
and III 266
Regulation of Transcription in
Eukaryotes 168
cis-Acting Regulatory Sequences:
Promoters and Enhancers 269
Transcription Factor Binding Sites 272
Transcriptional Regulatory Proteins 273
Structure and Function of Transcriptional
Activators 277
Eukaryotic Repressors 280
Relationship of Chromatin Structure to
Transcription 281
Regulation of Transcription by
Noncoding RNAs 285
DNA Methylation 286
RNA Processing and TUrnover 187
Processing of Ribosomal and Transfer
RNAs 287
Processing of mRNA in Eukaryotes 290
Splicing Mechanisms 292
Alternative Splicing 299
RNA Editing 300
RNA Degradation 301
• KEY EXPERIMENT Isolation of a
Eukaryotic Transcription Factor 276
CONTENTS ix
• KEY EXPERIMENT The Discovery
of snRNPs 294
Summary and Key Terms 303
Questions 306
References and Further Reading 306
8
Protein Synthesis,
Processing, and
Regulation 309
Translation of mRNA 309
Transfer RNAs 310
The Ribosome 311
The Organization of mRNAs and the
Initiation of Translation 317
The Process of Translation 319
Regulation of Translation 325
Protein Folding and Processing 319
Chaperones and Protein Folding 330
Enzymes that Catalyze Protein
Folding 332
Protem Cleavage 333
Glycosylation 335
Attachment of Lipids 337
Regulation of Protein Function 339
Regulation by Small Molecules 340
Protein Phosphorylation 341
Protein-Protein Interactions 344
Protein Degradation 344
The Ubiquitin-Proteasome Pathway 344
Lysosomal Proteolysis 347
• KEY EXPERIMENT Catalytic Role of
Ribosomal RNA 3 16
• MOLECULAR MEDICINE Antibiotic
Resistance and the Ribosome 320
Summary and Key Terms 348
Questions 350
References and Further Reading 350

PARr Ill Cell Structure and Fundion
9
The Nucleus 355
The Nuclear Envelope and Traffic
between the Nucleus and the
Cytoplasm 355
Structure of the Nuclear Envelope 356
The Nuclear Pore Complex 361
Selective Transport of Proteins to and
from the Nucleus 362
Regulation of Nuclear Protein
Import 368
Transport of RNAs 369
Internal Organization of the
Nucleus 371
Chromosomes and Higher-Order
Chromatin Structure 371
Sub-Compartments within the
Nucleus 374
The Nucleolus and rRNA
Processing 375
Ribosomal RNA Genes and the
Organization of the Nucleolus 376
Transcription and Processing
of rRNA 377
Ribosome Assembly 379
• KEY EXPERIMENT Identification of
Nuclear Localization Signals 364
• MOLECULAR MEDICINE Nuclear
Lamina Diseases 359
Summary and Key Terms 380
Questions 382
References and Further Reading 382
10
Protein Sorting and
Transport: The
Endoplasmic Reticulum,
Golgi Apparatus, and
Lysosomes 385
The Endoplasmic Reticulum 386
The Endoplasmic Reticulum and Protein
Secretion 386
Targeting Proteins to th~ Endoplasmic
Reticulum 387
Insertion of Proteins into the ER
Membrane 393
Protein Folding and Processing
in the ER 398
Quality Control in the ER 400
The Smooth ER and Lipid Synthesis 403
Export of Proteins and Lipids from the
ER 406
The Golgi Apparatus 408
Organization of the Golgi 409
Protein Glycosylation within the
Golgi 410
Lipid and Polysaccharide Metabolism
in the Golgi 413
Protein Sorting and Export from the
Golgi Apparatus 414
The Mechanism of Vesicular
Transport 417
Experimental Approaches to Understanding
Vesicular Transport 417
Cargo Selection, Coat Proteins. and
Vesicle Budding 419
Vesicle Fusion 420
Lysosomes 414
Lysosomal Acid Hydrolases 424
Endocytosis and Lysosome Formation 424
Phagocytosis and Autophagy 428
• KEY EXPERIMENT The Signal
Hypothesis 390
• MOLECULAR MEDICINE Gaucher
Disease 426
Summary and Key Terms 431
Questions 431
References and Further Reading 431
11
Bioenergetics and
Metabolism:
Mitochondria, Chloroplasts,
and Peroxisomes 433
Mitochondria 434
Organization and Function of
Mitochondria 434
The Genetic System of Mitochondria 435
Protein Import and Mitochondrial
Assembly 437
The Mechanism of Oxidative
Phosphorylation 443
The Electron Transport Chain 444
Chemiosmotic Coupling 445
Transport of Metabolites across the Inner
Membrane 450
Chloroplasts and Other Plastids 451
The Structure and Function of
Chloroplasts 451
The Chloroplast Genome 452
lmport and Sorting of Chloroplast
Proteins 454
Other Plastids 456
Photosynthesis 458
Electron Flow through Photosystems I
and II 459
Cyclic Electron Flow 461

ATP Synthesis 462
Peroxisomes 462
Functions of Peroxisomes 463
Peroxisome Assembly 465
• KEY EXPERIMENT The
Chemiosmotic Theory 448
• MOLECULAR MEDICINE Diseases of
Mitochondria: Leber’s Hereditary
Optic Neuropathy 438
Summary and Key Terms 467
Questions 469
References and Further Reading 470
12
The Cytoskeleton and
Cell Movement 471
Strudure and Organization of Adin
Filaments 473
Assembly and Disassembly of Actin
Filaments 474
Organization of Actin Filaments 480
Association of Actin Filaments with the
Plasma Membrane 482
Protrusions of the Cell Surface 485
Adin, Myosin, and Cell
Movement 486
Muscle Contraction 487
Contractile Assemblies of Actin and
Myosin in Nonmuscle Cells 491
Nonmuscle Myosins 493
Formation of Protrusions and Cell
Movement 495
Intermediate Filaments 497
Intermediate Filament Proteins 497
Assembly of Intermediate Filaments 498
Intracellular Organization of
Intermediate Filaments 499
Functions of Keratins and
Neurofilaments: Diseases of the Skin
and Nervous System 502
Microtubules 505
Structure and Dynamic Organization of
Microtubules 505
Assembly of Microtubules 507
Organization of Microtubules within
Cells 510
Microtubule Motors and
Movement 511
Identification of Microtubule Motor
Proteins 511
Cargo Transport and Intracellular
Organization 514
Cilia and Flagella 517
Reorganization of Microtubules during
Mitosis 520
Chromosome Movement 521
• KEY EXPERIMENT Expression of
Mutant Keratin Causes Abnormal
Skin Development 502
• KEY EXPERIMENT The Isolation of
Kinesin 514
Summary and Key Terms 523
Questions 526
References and Further Reading 526
13
The Plasma
Membrane 529
Strudure of the Plasma
Membrane 529
The Phospholipid Bilayer 530
Membrane Proteins 532
Mobility of Membrane Proteins 537
The Glycocalyx 540
Transport of Small Molecules 540
Passive Diffusion 541
Facilitated Diffusion and Carrier
Proteins 542
Ion Channels 543
Active Transport Driven by ATP
Hydrolysis 550
Active Transport Driven by Ion
Gradients 555
CONTENTS xi
Endocytosis 556
Phagocytosis 557
Receptor-Mediated Endocytosis 558
Protein Trafficking in Endocytosis 563
• KEY EXPERIMENT The LDL
Receptor 559
• MOLECULAR MEDICINE Cystic
Fibrosis 554
Summary and Key Terms 566
Questions 567
References and Further Reading 567
14
Cell Walls, the
Extracellular Matrix,
and Cell Interactions
569
Cell Walls 569
Bacterial Cell Walls 570
Eukaryotic Cell Walls 570
111e Extracellular Matrix and
Cell-Matrix lnteradions 575
Matrix Structural Proteins 575
Matrix Polysaccharides 578
Matrix Adhesion Proteins 579
Cell-Matrix Interactions 580
Ceii-Celllnteradions 584
Adhesion Junctions 584
Tight Junctions 588
Gap Junctions 589
Plasmodesmata 592
• KEY EXPERIMENT The
Characterization of lntegrin 582
• MOLECULAR MEDICINE Gap
Junction Diseases 591
Summary and Key Terms 593
Questions 594
References and Further Reading 595

P A R r ll,/ Cell Regulation
15
Cell Signaling 599
Signaling Molecules and Their
Receptors 600
Modes of Cell-Cell Signaling 600
Steroid Hormones and the Nuclear
Receptor Superfamily 601
Nitric Oxide and Carbon Monoxide 603
Neurotransmitters 604
Peptide Hormones and Growth
Factors 605
Eicosanoids 607
Plant Hormones 608
Functions of Cell Surface
Receptors 609
G Protein-Coupled Receptors 610
Receptor Protein-Tyrosine Kinases 612
Cytokine Receptors and Nonreceptor
Protein-Tyrosine Kinases 616
Receptors Linked to Other Enzymatic
Activities 616
Pathways of Intracellular Signal
Transduction 617
The cAMP Pathway: Second Messengers
and Protein Phosphorylation 618
Cyclic GMP 620
Phospholipids and Ca2• 621
The Pl 3-Kinase/ Akt and mTOR
Pathways 624
MAP Kinase Pathways 627
The JAK/STAT and TGF-/31Smad
Pathways 633
NF-KB Signaling 634
The Hedgehog, Wnt, and Notch
Pathways 634
Signal Transduction and the
Cytoskeleton 637
lntegrins and Signal Transduction 637
Regulation of the Actin Cytoskeleton 638
Signaling Networks 640
Feedback and Crosstalk 640
Networks of Cellular Signal
Transduction 641
• KEY EXPERIMENT The Src ProteinTyrosine
Kinase 6 12
• MOLECULAR MEDICINE Cancer:
Signal Transduction and the ras
Oncogenes 629
Summary and Key Terms 643
Questions 646
References and Further Reading 646
16
The Cell Cycle 649
The Eukaryotic Cell Cycle 650
Phases of the Cell Cycle 650
Regulation of the Cell Cycle by Cell
Growth and Extracellular Signals 652
Cell Cycle Checkpoints 654
Restricting DNA Replication to Once per
Cell Cycle 656
Regulators of Cell Cycle
Progression 657
Protein Kinases and Cell Cycle
Regulation 657
Families of C yclins and C yclinDependent
Kinases 661
Growth Factors and the Regulation of G
Cdk’s 665
1
DNA Damage Checkpoints 667
The Events of M Phase 669
Stages of Mitosis 669
Cdk1/Cyclin Band Progression to
Metaphase 672
The Spindle Assembly Checkpoint and
Progression to Anaphase 675
Cytokinesis 677
Meiosis and Fertilization 678
The Process of Meiosis 678
Regulation of Oocyte Meiosis 681
Fertilization 684
• KEY EXPERIMENT The Discovery of
MPF 658
• KEY EXPERIMENT The Identification
of Cyclin 662
Summary and Key Terms 685
Questions 687
References and Further Reading 687
17
Cell Death and Cell
Renewal 689
Programmed Cell Death 690
The Events of Apoptosis 690
Caspases: The Executioners of
Apoptosis 692
Central Regulators of Apoptosis:
The &l-2 Family 695
Signaling Pathways that Regulate
Apoptosis 698
Stem Cells and the Maintenance
of Adult Tissues 700
Proliferation of Differentiated Cells 700
Stem Cells 703
Medical Applications of Adult Stem
Cells 708
Embryonic Stem Cells and
Therapeutic Cloning 709
Embryonic Stem Cells 710
Somatic Cell Nuclear Transfer 713
• KEY EXPERIMENT Identification of
Genes Required for Programmed
Cell Death 694

• KEY EXPERIMENT Culture of
Embryonic Stem Cells 710
Summary and Key Terms 716
Questions 717
References and Further Reading 717
18
Cancer 719
The Development and Causes of
Cancer 719
Types of Cancer 720
The Development of Cancer 721
Causes of Cancer 723
Properties of Cancer Cells 724
Transformation of Cells in Culture 728
Tumor Viruses 729
Hepatitis Band C Viruses 729
SV40 and Polyomavirus 730
Papillomaviruses 731
Adenoviruses 731
Herpesviruses 732
Retroviruses 732
Oncogenes 733
Retroviral Oncogenes 734
Proto-Oncogenes 735
Oncogenes in Human Cancer 738
Functions of Oncogene Products 741
Tumor Suppressor Genes 746
Identification of Tumor Suppressor
Genes 746
Functions of Tumor Suppressor Gene
Products 750
Roles of Oncogenes and Tumor
Suppressor Genes in Tumor
Development 753
CONTENTS xiii
Molecular Approaches to cancer
Treatment 755
Prevention and Early Detection 755
Molecular Diagnosis 756
Treatment 756
• KEY EXPERIMENT The Discovery of
Proto-Oncogenes 737
• MOLECULAR MEDICINE ST/-571:
Cancer Treatment Targeted against
the bcr/abl Oncogene 759
Summary and Key Terms 761
Questions 763
References and Further Reading 763
Answers to Questions 767
Glossary 779
Index 799

File Size128 MB
File FormatPDF
Download  link Free Download | Become a Premium
Support Contact Us | Broken Link
Join Our Telegram Channel