Table of Contents
Table of Contents
1 Life Begins with Cells 1
1.1 The Diversity and Commonality of Cells 1
1.2 The Molecules of a Cell 8
1.3 The Work of Cells 13
1.4 Investigating Cells and Their Parts 19
1.5 A Genome Perspective on Evolution 26
2 Chemical Foundations 29
2.1 Atomic Bonds and Molecular Interactions 30
2.2 Chemical Building Blocks of Cells 37
2.3 Chemical Equilibrium 46
2.4 Biochemical Energetics 50
3 Protein Structure and Function 59
3.1 Hierarchical Structure of Proteins 60
3.2 Folding, Modification, and Degradation of Proteins 68
3.3 Enzymes and the Chemical Work of Cells 73
3.4 Molecular Motors and the Mechanical Work of Cells 79
3.5 Common Mechanisms for Regulating Protein Function 82
3.6 Purifying, Detecting, and Characterizing Proteins 86
4 Basic Molecular Genetic Mechanisms 101
4.1 Structure of Nucleic Acids 102
4.2 Transcription of Protein-Coding Genes and Formation of Functional mRNA 108
4.3 Control of Gene Expression in Prokaryotes 115
4.4 The Three Roles of RNA in Translation 119
4.5 Stepwise Synthesis of Proteins on Ribosomes 125
4.6 DNA Replication 131
4.7 Viruses: Parasites of the Cellular Genetic System 137
5 Biomembranes and Cell Architecture 147
5.1 Biomembranes: Lipid Composition and Structural Organization 149
5.2 Biomembranes: Protein Components and Basic Functions 157
5.3 Organelles of the Eukaryotic Cell 165
5.4 The Cytoskeleton: Components and Structural Functions 173
5.5 Purification of Cells and Their Parts 178
5.6 Visualizing Cell Architecture 184
6 Integrating Cells into Tissues 197
6.1 Cell-Cell and Cell-Matrix Adhesion: An Overview 199
6.2 Sheetlike Epithelial Tissues: Junctions and Adhesion Molecules 201
6.3 The Extracellular Matrix of Epithelial Sheets 209
6.4 The Extracellular Matrix of Nonepithelial Tissues 216
6.5 Adhesive Interactions and Nonepithelial Cells 223
6.6 Plant Tissues 231
6.7 Growth and Use of Cultured Cells 235
7 Transport of Ions and Small Molecules Across Cell Membranes 245
7.1 Overview of Membrane Transport 246
7.2 ATP-Powered Pumps and the Intracellular Ionic Environment 252
7.3 Nongated Ion Channels and the Resting Membrane Potential 260
7.4 Cotransport by Symporters and Antiporters 268
7.5 Movement of Water 271
7.6 Transepithelial Transport 274
7.7 Voltage-Gated Ion Channels and the Propagation of Action Potentials in Nerve Cells 276
7.8 Neurotransmitters and Receptor and Transport Proteins in Signal Transmission at Synapses 287
8 Cellular Energetics 301
8.1 Oxidation of Glucose and Fatty Acids to CO[subscript 2] 304
8.2 Electron Transport and Generation of the Proton-Motive Force 315
8.3 Harnessing the Proton-Motive Force for Energy-Requiring Processes 325
8.4 Photosynthetic Stages and Light-Absorbing Pigments 331
8.5 Molecular Analysis of Photosystems 336
8.6 CO[subscript 2] Metabolism During Photosynthesis 342
9 Molecular Genetic Techniques and Genomics 351
9.1 Genetic Analysis of Mutations to Identify and Study Genes 352
9.2 DNA Cloning by Recombinant DNA Methods 361
9.3 Characterizing and Using Cloned DNA Fragments 371
9.4 Genomics: Genome-wide Analysis of Gene Structure and Expression 380
9.5 Inactivating the Function of Specific Genes in Eukaryotes 387
9.6 Identifying and Locating Human Disease Genes 394
10 Molecular Structure of Genes and Chromosomes 405
10.1 Molecular Definition of a Gene 406
10.2 Chromosomal Organization of Genes and Noncoding DNA 408
10.3 Mobile DNA 414
10.4 Structural Organization of Eukaryotic Chromosomes 424
10.5 Morphology and Functional Elements of Eukaryotic Chromosomes 430
10.6 Organelle DNAs 438
11 Transcriptional Control of Gene Expression 447
11.1 Overview of Eukaryotic Gene Control and RNA Polymerases 448
11.2 Regulatory Sequences in Protein-Coding Genes 454
11.3 Activators and Repressors of Transcription 458
11.4 Transcription Initiation by RNA Polymerase II 469
11.5 Molecular Mechanisms of Transcription Activation and Repression 471
11.6 Regulation of Transcription-Factor Activity 481
11.7 Regulated Elongation and Termination of Transcription 485
11.8 Other Eukaryotic Transcription Systems 486
12 Post-transcriptional Gene Control and Nuclear Transport 493
12.1 Processing of Eukaryotic Pre-mRNA 493
12.2 Regulation of Pre-mRNA Processing 504
12.3 Macromolecular Transport Across the Nuclear Envelope 509
12.4 Cytoplasmic Mechanisms of Post-transcriptional Control 518
12.5 Processing of rRNA and tRNA 525
13 Signaling at the Cell Surface 533
13.1 Signaling Molecules and Cell-Surface Receptors 534
13.2 Intracellular Signal Transduction 541
13.3 G Protein-Coupled Receptors That Activate or Inhibit Adenylyl Cyclase 545
13.4 G Protein-Coupled Receptors That Regulate Ion Channels 555
13.5 G Protein-Coupled Receptors That Activate Phospholipase C 561
13.6 Activation of Gene Transcription by G Protein-Coupled Receptors 565
14 Signaling Pathways That Control Gene Activity 571
14.1 TGF[beta] Receptors and the Direct Activation on Smads 574
14.2 Cytokine Receptors and the JAK-STAT Pathway 578
14.3 Receptor Tyrosine Kinases and Activation of Ras 587
14.4 MAP Kinase Pathways 592
14.5 Phosphoinositides as Signal Transducers 598
14.6 Pathways That Involve Signal-Induced Protein Cleavage 601
14.7 Down-Modulation of Receptor Signaling 605
15 Integration of Signals and Gene Controls 611
15.1 Experimental Approaches for Building a Comprehensive View of Signal-Induced Responses 612
15.2 Responses of Cells to Environmental Influences 617
15.3 Control of Cell Fates by Graded Amounts of Regulators 621
15.4 Boundary Creation by Different Combinations of Transcription Factors 632
15.5 Boundary Creation by Extracellular Signals 639
15.6 Reciprocal Induction and Lateral Inhibition 644
15.7 Integrating and Controlling Signals 648
16 Moving Proteins into Membranes and Organelles 657
16.1 Translocation of Secretory Proteins Across the ER Membrane 659
16.2 Insertion of Proteins into the ER Membrane 666
16.3 Protein Modifications, Folding, and Quality Control in the ER 673
16.4 Export of Bacterial Proteins 680
16.5 Sorting of Proteins to Mitochondria and Chloroplasts 683
16.6 Sorting of Peroxisomal Proteins 693
17 Vesicular Traffic, Secretion, and Endocytosis 701
17.1 Techniques for Studying the Secretory Pathway 703
17.2 Molecular Mechanisms of Vesicular Traffic 707
17.3 Early Stages of the Secretory Pathway 715
17.4 Later Stages of the Secretory Pathway 719
17.5 Receptor-Mediated Endocytosis and the Sorting of Internalized Proteins 727
17.6 Synaptic Vesicle Function and Formation 735
18 Metabolism and Movement of Lipids 743
18.1 Phospholipids and Sphingolipids: Synthesis and Intracellular Movement 745
18.2 Cholesterol: A Multifunctional Membrane Lipid 750
18.3 Lipid Movement into and out of Cells 754
18.4 Feedback Regulation of Cellular Lipid Metabolism 763
18.5 The Cell Biology of Atherosclerosis, Heart Attacks, and Strokes 767
19 Microfilaments and Intermediate Filaments 779
19.1 Actin Structures 780
19.2 The Dynamics of Actin Assembly 784
19.3 Myosin-Powered Cell Movements 791
19.4 Cell Locomotion 800
19.5 Intermediate Filaments 805
20 Microtubules 817
20.1 Microtubule Organization and Dynamics 818
20.2 Kinesin- and Dynein-Powered Movements 829
20.3 Microtubule Dynamics and Motor Proteins in Mitosis 838
21 Regulating the Eukaryotic Cell Cycle 853
21.1 Overview of the Cell Cycle and Its Control 854
21.2 Biochemical Studies with Oocytes, Eggs, and Early Embryos 858
21.3 Genetic Studies with S. pombe 864
21.4 Molecular Mechanisms for Regulating Mitotic Events 868
21.5 Genetic Studies with S. cerevisiae 874
21.6 Cell-Cycle Control in Mammalian Cells 881
21.7 Checkpoints in Cell-Cycle Regulation 886
21.8 Meiosis: A Special Type of Cell Division 890
22 Cell Birth, Lineage, and Death 899
22.1 The Birth of Cells 900
22.2 Cell-Type Specification in Yeast 910
22.3 Specification and Differentiation of Muscle 913
22.4 Regulation of Asymmetric Cell Division 919
22.5 Cell Death and Its Regulation 924
23 Cancer 935
23.1 Tumor Cells and the Onset of Cancer 936
23.2 The Genetic Basis of Cancer 943
23.3 Oncogenic Mutations in Growth-Promoting Proteins 951
23.4 Mutations Causing Loss of Growth-Inhibiting and Cell-Cycle Controls 956
23.5 The Role of Carcinogens and DNA Repair in Cancer 961
Glossary
Index