fourth editio n molecular cell biology - gbv · 2011-09-29 · fourth editio n molecular cell...
TRANSCRIPT
FOURTH EDITIO N
MOLECULA RCEL LBIOLOGY Harvey Lodis h
Arnold Berk
S . Lawrence Zipursky
Paul Matsudaira
:iAtrov 1
4 '
David Baltimore
James Darnell
PART I Laying the Groundwork
PART III Building and Fuelin gthe Cell
1
The Dynamic Cell 1
2
Chemical Foundations 14
15 Transport across Cell Membranes 578
3
Protein Structure and Function 50
16 Cellular Energetics : Glycolysis, Aerobi c
Oxidation, and Photosynthesis 61 6
4
Nucleic Acids, the Genetic Code, and the
Synthesis of Macromolecules 100
17 Protein Sorting: Organelle Biogenesis an d
Protein Secretion 675
5
Biomembranes and the Subcellular
Organization of Eukaryotic Cells 138
18 Cell Motility and Shape I:
Microfilaments 751
6
Manipulating Cells and Viruses in
Culture 180
19 Cell Motility and Shape II : Microtubule s
and Intermediate Filaments 79 5
7
Recombinant DNA and Genomics 20 7
8
Genetic Analysis in Cell Biology 254
PART IV Cell Interactions
PART II Nuclear Control of
20 Cell-to-Cell Signaling: Hormones and
Cellular Activity
Receptors 848
21 Nerve Cells 91 1
9
Molecular Structure of Genes an d
Chromosomes 294
22 Integrating Cells into Tissues 968
10 Regulation of Transcription Initiation 341
23 Cell Interactions in Development 100 3
11 RNA Processing, Nuclear Transport, and
24 Cancer 1054
Post-Transcriptional Control 404
12 DNA Replication, Repair, and
Recombination 453
13 Regulation of the Eukaryotic Cell Cycle 495
14 Gene Control in Development 537
Chapter-Opening Illustrations xxxvii
Asymmetric Carbon Atoms Are Present in Most Biologica lMolecules 1 9
a and /3 Glycosidic Bonds Link Monosaccharides 2 1PART I : Laying the Groundwork
2 .2 Noncovalent Bonds 2 2
The Hydrogen Bond Underlies Water's Chemical and
1 The Dynamic Cell
Biological Properties 22
Ionic Interactions Are Attractions between Oppositel y1 .1 Evolution : At the Core of Molecular Change 3
Charged Ions 2 3
Van der Waals Interactions Are Caused by Transient1 .2 The Molecules of Life 3
Dipoles 2 4
1.3 The Architecture of Cells 5
Hydrophobic Bonds Cause Nonpolar Molecules to Adher e
Cells Are Surrounded by Water-Impermeable
to One Another 2 5
Membranes 5
Multiple Noncovalent Bonds Can Confer Binding
Membranes Serve Functions Other Than Segregation 6
Specificity 2 6
Prokaryotes Comprise a Single Membrane-Limited
Phospholipids Are Amphipathic Molecules 2 6
Compartment 7
The Phospholipid Bilayer Forms the Basic Structure of Al l
Eukaryotic Cells Contain Many Organelles and a
Biomembranes 2 7
Complex Cytoskeleton 7
2 .3 Chemical Equilibrium 29Cellular DNA Is Packaged within Chromosomes 8
Equilibrium Constants Reflect the Extent of a Chemica l1 .4 The Life Cycle of Cells 9
Reaction 2 9
The Cell Cycle Follows a Regular Timing Mechanism 9
The Concentration of Complexes Can Be Estimated fro m
Mitosis Apportions the Duplicated Chromosomes Equally
Equilibrium Constants for Binding Reactions 3 1
to Daughter Cells 10
Biological Fluids Have Characteristic pH Values 3 1
Cell Differentiation Creates New Types of Cells 10
Hydrogen Ions Are Released by Acids and Taken Up b y
Cells Die by Suicide 10
Bases 32
The Henderson-Hasselbalch Equation Relates pH and K e q1 .5 Cells into Tissues 11
of an Acid-Base System 3 3Multicellularity Requires Extracellular Glues 11
Buffers Maintain the pH of Intracellular and Extracellula rTissues Are Organized into Organs 11
Fluids 33
Body Plan and Rudimentary Tissues Form Early in
2 .4 Biochemical Energetics 3 5Embryonic Development 12
Living Systems Use Various Forms of Energy, Which Ar e1 .6 Molecular Cell Biology : An Integrated View of Cells
Interconvertible 3 5
at Work 13
The Change in Free Energy AG Determines the Directio n
MEDIA CONNECTIONS of a Chemical Reaction 3 6
Overview: Life Cycle of a Cell
The AG of a Reaction Depends on Changes in Enthalpy(Bond Energy) and Entropy 3 6
Several Parameters Affect the AG of a Reaction 3 7
2 Chemical Foundations
The AG° ' of a Reaction Can Be Calculated from Its K eq 3 8
Cells Must Expend Energy to Generate Concentratio n2.1 Covalent Bonds 15
Gradients 3 9Each Atom Can Make a Defined Number of Covalent
Many Cellular Processes Involve Oxidation-Reductio nBonds 16
Reactions 3 9The Making or Breaking of Covalent Bonds Involves
An Unfavorable Chemical Reaction Can Proceed If It I sLarge Energy Changes 17
Coupled with an Energetically Favorable Reaction 4 1Covalent Bonds Have Characteristic Geometries 17
Hydrolysis of Phosphoanhydride Bonds in ATP Release sElectrons Are Shared Unequally in Polar Covalent
Substantial Free Energy 4 1Bonds 18
ATP Is Used to Fuel Many Cellular Processes 43
2.5 Activation Energy and Reaction Rate 45
3 .4 Membrane Proteins 7 8Chemical Reactions Proceed through High-Energy
Proteins Interact with Membranes in Different Ways 7 8Transition States 45
Hydrophobic a Helices in Transmembrane Proteins AreEnzymes Accelerate Biochemical Reactions by Reducing
Embedded in the Bilayer 7 9Transition-State Free Energy 47
Many Integral Proteins Contain Multiple Transmembran eMEDIA CONNECTIONS
a Helices 79
Overview: Biological Energy Interconversions
Multiple ß Strands in Porins Form Membrane-Spannin g"Barrels " 8 1
Covalently Attached Hydrocarbon Chains Anchor SomeProteins to the Membrane 8 1
3 Protein Structure and Function
Some Peripheral Proteins Are Soluble Enzymes That Ac t
3 .1 Hierarchical Structure of Proteins 51
on Membrane Components 82
The Amino Acids Composing Proteins Differ Only in
3 .5 Purifying, Detecting, and Characterizing
Their Side Chains 51
Proteins 83
Peptide Bonds Connect Amino Acids into Linear
Proteins Can Be Removed from Membranes by DetergentsChains 53
or High-Salt Solutions 8 3
Four Levels of Structure Determine the Shape of
Centrifugation Can Separate Particles and Molecules That
Proteins 54
Differ in Mass or Density 8 5
Graphic Representations of Proteins Highlight Different
Electrophoresis Separates Molecules according to Thei r
Features 54
Charge :Mass Ratio 87
Secondary Structures Are Crucial Elements of Protein
Liquid Chromatography Resolves Proteins by Mass,
Architecture 56
Charge, or Binding Affinity 8 8
Motifs Are Regular Combinations of Secondary
Highly Specific Enzyme and Antibody Assays Can Detect
Structures 58
Individual Proteins 90
Structural and Functional Domains Are Modules of
Radioisotopes Are Indispensable Tools for Detectin g
Tertiary Structure 60
Biological Molecules 90
Sequence Homology Suggests Functional and Evolutionary
Protein Primary Structure Can Be Determined b y
Relationships between Proteins 60
Chemical Methods and from Gene Sequences 9 4
Time-of-Flight Mass Spectrometry Measures the Mass o f3 .2 Folding, Modification, and Degradation of
Proteins and Peptides 94Proteins 62
Peptides with a Defined Sequence Can Be Synthesize dThe Information for Protein Folding Is Encoded in the
Chemically 94Sequence 63
Protein Conformation Is Determined by Sophisticate dFolding of Proteins in Vivo Is Promoted by
Physical Methods 9 5Chaperones 63
Chemical Modifications and Processing Alter theMEDIA CONNECTIONS
Biological Activity of Proteins 64
Focus: Chaperone-Mediated Foldin g
Cells Degrade Proteins via Several Pathways 66
Overview: Life Cycle of a Protein
Technique: 5DS Gel ElectrophoresisAberrantly Folded Proteins Are Implicated in Slowly
Developing Diseases 67
Technique: Immunoblotting
Classical Experiment 3.1 : Bringing an Enzyme Back
3.3 Functional Design of Proteins 68
to Life
Proteins Are Designed to Bind a Wide Range ofMolecules 6 8
Antibodies Exhibit Precise Ligand Binding
4 Nucleic Acids, the Genetic
Specificity 70
Code, and the SynthesisEnzymes Are Highly Efficient and Specific Catalysts 71
of MacromoleculesAn Enzyme 's Active Site Binds Substrates and Carries Out
Catalysis 71
4.1 Structure of Nucleic Acids 10 1
Kinetics of an Enzymatic Reaction Are Described by V,,,ax
Polymerization of Nucleotides Forms Nucleic Acids 10 1
and Km 73
Native DNA Is a Double Helix of Complementary
Many Proteins Contain Tightly Bound Prosthetic
Antiparallel Chains 103
Groups 74
DNA Can Undergo Reversible Strand Separation 10 5
A Variety of Regulatory Mechanisms Control Protein
Many DNA Molecules Are Circular 10 7
Function 75
Local Unwinding of DNA Induces Supercoiling 108
RNA Molecules Exhibit Varied Conformations an dFunctions 108
5 Biomembranes and th eSubcellular Organization
4.2 Synthesis of Biopolymers : Rules of Macromolecula rCarpentry 110
of Eukaryotic Cells
4.3 Nucleic Acid Synthesis 111
5 .1 Microscopy and Cell Architecture 14 0
Both DNA and RNA Chains Are Produced by Copying of
Light Microscopy Can Distinguish Objects Separated b y
Template DNA Strands 111
0 .2 µm or More 140
Nucleic Acid Strands Grow in the 5'
3'
Samples for Light Microscopy Usually Are Fixed,
Direction 112
Sectioned, and Stained 14 1
RNA Polymerases Can Initiate Strand Growth but DNA
Fluorescence Microscopy Can Localize and Quantify
Polymerases Cannot 112
Specific Molecules in Cells 14 2
Replication of Duplex DNA Requires Assembly of Many
Confocal Scanning and Deconvolution Microscop y
Proteins at a Growing Fork 113
Provide Sharper Images of Three-Dimensiona l
Organization of Genes in DNA Differs in Prokaryotes and
Objects 144
Eukaryotes 114
Phase-Contrast and Nomarski Interference Microscop y
Eukaryotic Primary RNA Transcripts Are Processed to
Visualize Unstained Living Cells 14 6
Form Functional mRNAs 115
Transmission Electron Microscopy Has a Limit o fResolution of 0 .1 nm 14 7
4.4 The Three Roles of RNA in Protein
Scanning Electron Microscopy Visualizes Details on th eSynthesis 116
Surfaces of Cells and Particles 15 2Messenger RNA Carries Information from DNA in a
Three-Letter Genetic Code 117
5.2 Purification of Cells and Their Parts 15 2Experiments with Synthetic mRNAs and Trinucleotides
Flow Cytometry Separates Different Cell Types 15 3Broke the Genetic Code 119
Disruption of Cells Releases Their Organelles and Othe rThe Folded Structure of tRNA Promotes Its Decoding
Contents 153Functions 120
Different Organelles Can Be Separated b yNonstandard Base Pairing Often Occurs between Codons
Centrifugation 154and Anticodons 122
Organelle-Specific Antibodies Are Useful in Preparin gAminoacyl-tRNA Synthetases Activate Amino Acids by
Highly Purified Organelles 15 7Linking Them to tRNAs 12 3
Each tRNA Molecule Is Recognized by a Specific
5.3 Biomembranes : Structural Organization and Basi cAminoacyl-tRNA Synthetase 124
Functions 15 7Ribosomes Are Protein-Synthesizing Machines 125
Phospholipids Are the Main Lipid Constituents of Mos tBiomembranes 15 7
4.5 Stepwise Formation of Proteins on Every Cellular Membrane Forms a Closed Compartmen tRibosomes 128
and Has a Cytosolic and an Exoplasmic Face 16 0The AUG Start Codon Is Recognized by Methionyl-
Several Types of Evidence Point to the Universality of th etRNAm, et 128
Phospholipid Bilayer 16 0Bacterial Initiation of Protein Synthesis Begins Near a
All Integral Proteins and Glycolipids Bind Asymmetricall yShine-Dalgarno Sequence in mRNA 129
to the Lipid Bilayer 16 2Eukaryotic Initiation of Protein Synthesis Occurs at the 5'
The Phospholipid Composition Differs in Two Membran eEnd and Internal Sites in mRNA 130
Leaflets 162During Chain Elongation Each Incoming Aminoacyl-
Most Lipids and Integral Proteins Are Laterally Mobile i ntRNA Moves through Three Ribosomal Sites 131
Biomembranes 162Protein Synthesis Is Terminated by Release Factors When
Fluidity of Membranes Depends on Temperature an da Stop Codon Is Reached 132
Composition 164Simultaneous Translation by Multiple Ribosomes and
Membrane Leaflets Can Be Separated and Each Fac eTheir Rapid Recycling Increase the Efficiency of
Viewed Individually 16 5Protein Synthesis 133
The Plasma Membrane Has Many Common Functions i nMEDIA CONNECTIONS
All Cells 16 6Focus: Basic Transcriptional Mechanism
Overview: Life Cycle of an mRNA
5 .4 Organelles of the Eukaryotic Cell 16 8Focus: Protein Synthesis
Lysosomes Are Acidic Organelles That Contain a Batter yClassic Experiment 4.1 : Cracking the Genetic Code
of Degradative Enzymes 169
Plant Vacuoles Store Small Molecules and Enable the Cell
Animal Viruses Are Classified by Genome Type an dto Elongate Rapidly 170
mRNA Synthesis Pathway 19 9Peroxisomes Degrade Fatty Acids and Toxic
Viral Vectors Can Be Used to Introduce Specific Gene sCompounds 171
into Cells 20 3
Mitochondria Are the Principal Sites of ATP Production
MEDIA CONNECTION Sin Aerobic Cells 171
Technique: Preparing Monoclonal Antibodie sChloroplasts, the Sites of Photosynthesis, Contain Three
Overview: Life Cycle of a Retroviru sMembrane Limited Compartments 172
Classic Experiment 6.1 : The Discovery of ReverseThe Endoplasmic Reticulum Is a Network of
TranscriptaseInterconnected Internal Membranes 17 2
Golgi Vesicles Process and Sort Secretory and Membran eProteins 173
7 Recombinant DNA and GenomicsThe Double-Membraned Nucleus Contains the Nucleolu s
and a Fibrous Matrix 174
7.1 DNA Cloning with Plasmid Vectors 20 8The Cytosol Contains Many Particles and Cytoskeletal
Plasmids Are Extrachromosomal Self-Replicating DN AFibers 175
Molecules 209
MEDIA CONNECTIONS
E . Coll Plasmids Can Be Engineered for Use as Clonin g
Overview: Protein Secretion
Vectors 20 9
Technique: Reporter Constructs
Plasmid Cloning Permits Isolation of DNA Fragment s
Classic Experiment 5 .1: Separating Organellesfrom Complex Mixtures 210
Restriction Enzymes Cut DNA Molecules at Specifi cSequences 21 1
6 Manipulating Cells and
Restriction Fragments with Complementary "Sticky Ends "Are Ligated Easily 21 2
Viruses in Culture
Polylinkers Facilitate Insertion of Restriction Fragment s
6 .1 Growth of Microorganisms in Culture 181
into Plasmid Vectors 214
Many Microorganisms Can Be Grown in Minimal
Small DNA Molecules Can Be Chemically
Medium 181
Synthesized 215
Mutant Strains of Bacteria and Yeast Can Be Isolated by
7 .2 Constructing DNA Libraries with A Phage and
Replica Plating 182
Other Cloning Vectors 21 6
Bacteriophage A Can Be Modified for Use as a Cloning6.2 Growth of Animal Cells in Culture 183
Vector and Assembled in Vitro 21 6Rich Media Are Required for Culture of Animal Cells 183
Nearly Complete Genomic Libraries of Higher Organism s
Most Cultured Animal Cells Grow Only on Special Solid
Can Be Prepared by A Cloning 21 8Surfaces 183
cDNA Libraries Are Prepared from Isolate dPrimary Cell Cultures Are Useful, but Have a Finite Life
mRNAs 21 9Span 185
Larger DNA Fragments Can Be Cloned in Cosmids an d
Transformed Cells Can Grow Indefinitely in
Other Vectors 22 1Culture 18 6
Fusion of Cultured Animal Cells Can Yield Interspecific
7 .3 Identifying, Analyzing, and Sequencin g
Hybrids Useful in Somatic-Cell Genetics 187
Cloned DNA 223
Hybrid Cells Often Are Selected in HAT Medium 189
Libraries Can Be Screened with Membrane Hybridizatio n
Hybridomas Are Used to Produce Monoclonal
Assay 224
Antibodies 189
Oligonucleotide Probes Are Designed Based on Partia l
Protein Sequences 225
6.3 Viruses : Structure, Function, and Uses 191
Specific Clones Can Be Identified Based on Properties of
Viral Capsids Are Regular Arrays of One or a Few Types
the Encoded Proteins 22 7
of Protein 192
Gel Electrophoresis Resolves DNA Fragments of Differen t
Most Viral Host Ranges Are Narrow 194
Size 22 8
Viruses Can Be Cloned and Counted in Plaque
Multiple Restriction Sites Can Be Mapped on a Clone d
Assays 194
DNA Fragment 23 0
Viral Growth Cycles Are Classified as Lytic or
Pulsed-Field Gel Electrophoresis Separates Large DN A
Lysogenic 194
Molecules 23 1
Four Types of Bacterial Viruses Are Widely Used in
Purified DNA Molecules Can Be Sequenced Rapidly b y
Biochemical and Genetic Research 196
Two Methods 231
7.4 Bioinformatics 235
Mutations Occur Spontaneously and Can B e
Stored Sequences Suggest Functions of Newly Identified
Induced 25 7
Genes and Proteins 235
Some Human Diseases Are Caused by Spontaneou s
Comparative Analysis of Genomes Reveals Much about
Mutations 25 8
an Organism's Biology 236
8 .2 Isolation and Analysis of Mutants 26 1Homologous Proteins Involved in Genetic Information
Temperature-Sensitive Screens Can Isolate Letha lProcessing Are Widely Distributed 238
Mutations in Haploids 26 1Many Yeast Genes Function in Intracellular Protein
Recessive Lethal Mutations in Diploids Can Be ScreenedTargeting and Secretion 239
by Use of Visible Markers 26 3The C. elegans Genome Encodes Numerous Proteins
Complementation Analysis Determines If Differen tSpecific to Multicellular Organisms 239
Mutations Are in the Same Gene 26 4
7.5 Analyzing Specific Nucleic Acids in Complex
Metabolic and Other Pathways Can Be Generically
Mixtures 240
Dissected 265
Southern Blotting Detects Specific DNA Fragments 240
Suppressor Mutations Can Identify Genes Encodin gInteracting Proteins 265
Northern Blotting Detects Specific RNAs 24 1
Specific RNAs Can Be Quantitated and Mapped on DNA
8 .3 Genetic Mapping of Mutations 26 6
by Nuclease Protection 241
Segregation Patterns Indicate Whether Mutations Are o n
Transcription Start Sites Can Be Mapped by Si Protection
the Same or Different Chromosomes 26 7
and Primer Extension 243
Chromosomal Mapping Locates Mutations on Particula rChromosomes 26 8
7 .6 Producing High Levels of Proteins from Cloned
Recombinational Analysis Can Map Genes Relative t ocDNAs 244
Each Other on a Chromosome 26 9F. coli Expression Systems Can Produce Full-Length
DNA Polymorphisms Are Used to Map Huma nProteins 244
Mutations 27 1Eukaryotic Expression Systems Can Produce Proteins with
Some Chromosomal Abnormalities Can Be Mapped byPost-Translational Modifications 245
Banding Analysis 272Cloned cDNAs Can Be Translated in Vitro to Yield
8 .4 Molecular Cloning of Genes Defined byLabeled Proteins 245
Mutations 2747.7 Polymerase Chain Reaction : An Alternative
Cloned DNA Segments Near a Gene of Interest Ar eto Cloning 246
Identified by Various Methods 27 4
PCR Amplification of Mutant Alleles Permits Their
Chromosome Walking Is Used to Isolate a Limited Regio nDetection in Small Samples 246
of Contiguous DNA 27 5
DNA Sequences Can Be Amplified for Use in Cloning and
Physical Maps of Entire Chromosomes Can Beas Probes 247
Constructed by Screening YAC Clones for Sequence -Tagged Sites 276
7 .8 DNA Microarrays : Analyzing Genome-Wide
Physical and Genetic Maps Can Be Correlated with th eExpression 248
Aid of Known Markers 277MEDIA CONNECTIONS
Further Analysis Is Needed to Locate a Mutation-Define dTechnique: Plasmid Cloning
Gene in Cloned DNA 27 8Technique: Dideoxy Sequencing of DNA
Protein Structure Is Deduced from cDNA Sequence 27 9Technique: Polymerase Chain Reaction
8 .5 Gene Replacement and Transgenic Animals 28 1Classic Experiment 7 .1 : Unleashing the Power of
Specific Sites in Cloned Genes Can Be Altered i nExponential Growth: The Polymerase Chain
Vitro 28 1Reactio n
Classic Experiment 7 .2: Demonstrating Sequence-
DNA Is Transferred into Eukaryotic Cells in Variou s
Specific Cleavage by a Restriction Enzyme
Ways 28 2
Normal Genes Can Be Replaced with L1utant Alleles i nYeast and Mice 28 2
8 Genetic Analysis in Cell Biology
Foreign Genes Can Be Introduced into Plants an dAnimals 287
8 .1 Mutations : Types and Causes 255
MEDIA CONNECTION SMutations Are Recessive or Dominant 255
Technique: In Vitro Mutagenesis of Cloned Gene sInheritance Patterns of Recessive and Dominant
Technique : Creating a Transgenic Mous eMutations Differ 256
Classic Experiment 8 .1 : Expressing Foreign GenesMutations Involve Large or Small DNA Alterations 257
in Mice
PART II : Nuclear Control of
9.5 Organizing Cellular DNA into Chromosomes 32 0Cellular Activity
Most Bacterial Chromosomes Are Circular with On eReplication Origin 32 0
Eukaryotic Nuclear DNA Associates with Histon eProteins to Form Chromatin 32 1
9 Molecular Structure of Genes and
Chromatin Exists in Extended and Condense dForms 321Chromosomes
Acetylation of Histone N-Termini Reduces Chromati nCondensation 3239.1 Molecular Definition of a Gene 295
Eukaryotic Chromosomes Contain One Linear DN ABacterial Operons Produce Polycistronic mRNAs 295
Molecule 32 4Most Eukaryotic mRNAs Are Monocistronic and Contai n
Introns 295
Simple and Complex Transcription Units Are Found in
9 .6 Morphology and Functional Elements of Eukaryoti cEukaryotic Genomes 296
Chromosomes 32 4
Chromosome Number, Size, and Shape at Metaphase Are9.2 Chromosomal Organization of Genes and
Species Specific 32 5Noncoding DNA 297
Nonhistone Proteins Provide a Structural Scaffold fo rGenomes of Higher Eukaryotes Contain Much
Long Chromatin Loops 32 5Nonfunctional DNA 297
Chromatin Contains Small Amounts of Other Proteins i nCellular DNA Content Does Not Correlate with
Addition to Histones and Scaffold Proteins 32 7Phylogeny 298
Stained Chromosomes Have Characteristic BandingProtein-Coding Genes May Be Solitary or Belong to a
Patterns 327Gene Family 299
Chromosome Painting Distinguishes Each Homologou sTandemly Repeated Genes Encode rRNAs, tRNAs, and
Pair by Color 328Histones 300
Heterochromatin Consists of Chromosome Regions Tha tReassociation Experiments Reveal Three Major Fractions
Do Not Uncoil 32 9of Eukaryotic DNA 301
Three Functional Elements Are Required for Replicatio nSimple-Sequence DNAs Are Concentrated in Specific
and Stable Inheritance of Chromosomes 329Chromosomal Locations 301
Yeast Artificial Chromosomes Can Be Used to Clon eDNA Fingerprinting Depends on Differences in Length of
Megabase DNA Fragments 33 1Simple-Sequence DNAs 30 2
9.3 Mobile DNA 303
9.7 Organelle DNAs 33 2
Movement of Mobile Elements Involves a DNA or RNA
Mitochondria Contain Multiple mtDNA Molecules 33 2
Intermediate 304
Genes in mtDNA Exhibit Cytoplasmic Inheritance an d
Mobile Elements That Move as DNA Are Present in
Encode rRNAs, tRNAs, and Some Mitochondria l
Prokaryotes and Eukaryotes 304
Proteins 33 3
Viral Retrotransposons Contain LTRs and Behave Like
The Size and Coding Capacity of mtDNA Var y
Retroviruses in the Genome 307
Considerably in Different Organisms 33 4
Nonviral Retrotransposons Lack LTRs and Move by an
Products of Mitochondrial Genes Are No t
Unusual Mechanism 308
Exported 335
Retrotransposed Copies of Cellular RNAs Occur in
Mitochondrial Genetic Codes Differ from the Standard
Eukaryotic Chromosomes 312
Nuclear Code 335
Mobile DNA Elements Probably Had a Significant
Mutations in Mitochondrial DNA Cause Several Genetic
Influence on Evolution 312
Diseases in Man 33 6
Chloroplasts Contain Large Circular DNAs Encodin g
9.4 Functional Rearrangements in Chromosomal
More Than a Hundred Proteins 33 6
DNA 314
MEDIA CONNECTION SInversion of a Transcription-Control Region Switches
Focus: Retroviral Reverse Transcription
Salmonella Flagellar Antigens 314
Focus: Three-Dimensional Packing of Nuclear
Antibody Genes Are Assembled by Rearrangements of
Chromosomes
Germ-Line DNA 315
Classic Experiment 9.1 : Two Genes Become One:
Generalized DNA Amplification Produces Polytene
Somatic Rearrangement of Immunoglobin
Chromosomes 318
Genes
10 Regulation of Transcription
RNA Polymerase II Initiates Transcription at DN ASequences Corresponding to the 5' Cap o f
Initiation
mRNAs 36 2
10.1 Bacterial Gene Control : The Jacob-Monod
10 .4 Regulatory Sequences in Eukaryotic Protein-Codin gModel 342
Genes 365Enzymes Encoded at the lac Operon Can Be Induced
TATA Box, Initiators, and CpG Islands Function a sand Repressed 342
Promoters in Eukaryotic DNA 36 5
Mutations in lac? Cause Constitutive Expression of lac
Promoter-Proximal Elements Help Regulate Eukaryoti cOperon 343
Genes 366
Isolation of Operator Constitutive and Promoter
Transcription by RNA Polymerase II Often Is Stimulate dMutants Support Jacob-Monod Model 343
by Distant Enhancer Sites 36 8
Regulation of lac Operon Depends on Cis-Acting DNA
Most Eukaryotic Genes Are Regulated by Multipl eSequences and Trans-Acting Proteins 344
Transcription-Control Elements 36 9Biochemical Experiments Confirm That Induction of th e
lac Operon Leads to Increased Synthesis of lac
10 .5 Eukaryotic Transcription Activators an dmRNA 344
Repressors 370Biochemical and Genetic Techniques Have Been Used t o
10.2 Bacterial Transcription Initiation 346
Identify Transcription Factors 370Footprinting and Gel-Shift Assays Identify Protein-DNA
Transcription Activators Are Modular Proteins Compose dInteractions 346
of Distinct Functional Domains 372The lac Control Region Contains Three Critical Cis-
DNA-Binding Domains Can Be Classified int oActing Sites 347
Numerous Structural Types 37 3RNA Polymerase Binds to Specific Promoter Sequences
Heterodimeric Transcription Factors Increase Gene -to Initiate Transcription 347
Control Options 376Differences in E. coli Promoter Sequences Affect
Activation Domains Exhibit Considerable Structura lFrequency of Transcription Initiation 349
Diversity 377Binding of lac Repressor to the lac Operator Blocks
Multiprotein Complexes Form on Enhancers 37 8Transcription Initiation 349 Many Repressors Are the Functional Converse o f
Most Bacterial Repressors Are Dimers Containing a
Activators 37 9Helices That Insert into Adjacent Major Grooves o f
Operator DNA 349
10 .6 RNA Polymerase II Transcription-Initiation
Ligand-Induced Conformational Changes Alter Affinity
Complex 38 0of Many Repressors for DNA 352
Initiation by Pol II Requires General Transcription
Positive Control of the lac Operon Is Exerted by cAMP-
Factors 38 1
CAP 352
Proteins Comprising the Pol II Transcription-Initiatio n
Cooperative Binding of cAMP-CAP and RNA
Complex Assemble in a Specific Order in Vitro 38 1
Polymerase to lac Control Region Activates
A Pol II Holoenzyme Multiprotein Complex Functions i n
Transcription 353
Vivo 383
Transcription Control at All Bacterial Promoters Involve sSimilar but Distinct Mechanisms 354
10 .7 Molecular Mechanisms of Eukaryoti c
Transcription from Some Promoters Is Initiated by
Transcriptional Control 38 4
Alternative Sigma (v) Factors 355
N-Termini of Histones in Chromatin Can B eModified 38 4
Many Bacterial Responses Are Controlled by Two -Component Regulatory Systems 356
Formation of Heterochromatin Silences Gene Expressio nat Telomeres and Other Regions 38 4
10 .3 Eukaryotic Gene Control : Purposes and General
Repressors Can Direct Histone Deacetylation at Specific
Principles 358
Genes 38 7
Most Genes in Higher Eukaryotes Are Regulated by
Activators Can Direct Histone Acetylation at Specifi cControlling Their Transcription 358
Genes 38 9
Regulatory Elements in Eukaryotic DNA Often Are
Chromatin-Remodeling Factors Participate in Activatio nMany Kilobases from Start Sites 360
at Some Promoters 390
Three Eukaryotic Polymerases Catalyze Formation of
Activators Stimulate the Highly Cooperative Assembly o f
Different RNAs 361
Initiation Complexes 39 0
The Largest Subunit in RNA Polymerase II Has an
Repressors Interfere Directly with Transcriptio nEssential Carboxyl-Terminal Repeat 362
Initiation in Several Wavs 391
Regulation of Transcription-Factor Expression
Portions of Two Different RNAs Are Trans-Spliced i nContributes to Gene Control 392
Some Organisms 41 8Lipid-Soluble Hormones Control the Activities of
Self-Splicing Group II Introns Provide Clues to theNuclear Receptors 392
Evolution of snRNAs 41 9Polypeptide Hormones Signal Phosphorylation of Some
Most Transcription and RNA Processing Occur in aTranscription Factors 394
Limited Number of Domains in Mammalian Cel lNuclei 42010.8 Other Transcription Systems 39 7
Transcription Initiation by Pol I and Pol III Is Analogous
11 .3 Regulation of mRNA Processing 422to That by Pol II 397
U1A Protein Inhibits Polyadenylation of Its Pre -T7 and Related Bacteriophages Express Monomeric,
mRNA 422Largely Unregulated RNA Polymerases 398
Tissue-Specific RNA Splicing Controls Expression o fMitochondrial DNA Is Transcribed by RNA Polymerases
Alternative Fibronectins 42 3with Similarities to Bacteriophage and Bacterial
A Cascade of Regulated RNA Splicing Control sEnzymes 398
Drosophila Sexual Differentiation 42 3Transcription of Chloroplast DNA Resembles Bacterial
Multiple Protein Isoforms Are Common in theTranscription 399
Vertebrate Nervous System 42 5Transcription by Archaeans Is Closer to Eukaryotic Than
to Bacterial Transcription 399
11 .4 Signal-Mediated Transport through Nuclear Por eMEDIA CONNECTIONS
Complexes 426Focus: Combinatorial Control of Transcription
Nuclear Pore Complexes Actively Transpor tMacromolecules between the Nucleus andCytoplasm 427
11 RNA Processing,
Receptors for Nuclear-Export Signals Transport Proteinsand mRNPs out of the Nucleus 42 8
Nuclear Transport, and Post-
Pre-mRNAs in Spliceosomes Are Not Exported from theTranscriptional Control
Nucleus 43 1
Receptors for Nuclear-Localization Signals Transpor t11 .1 Transcription Termination 405
Proteins into the Nucleus 432Rho-Independent Termination Occurs at Characteristic
Various Nuclear-Transport Systems Utilize Simila rSequences in E . cull DNA 405
Proteins 434Premature Termination by Attenuation Helps Regulate
HIV Rev Protein Regulates the Transport of Unsplice dExpression of Some Bacterial Operons 405
Viral mRNAs 435Rho-Dependent Termination Sites Are Present in Som e
A-Phage and E. coli Genes 407
11 .5 Other Mechanisms of Post-Transcriptiona lSequence-Specific RNA-Binding Proteins Can Regulate
Control 436Termination by E. coli RNA Polymerase 407
RNA Editing Alters the Sequences of Pre-mRNAs 43 7Three Eukaryotic RNA Polymerases Employ Different
Some mRNAs Are Associated with Cytoplasmi cTermination Mechanisms 408
Structures or Localized to Specific Regions 43 8Transcription of HIV Genome Is Regulated by an
Stability of Cytoplasmic mRNAs Varies Widely 440Antitermination Mechanism 409
II
Degradation Rate of Some Eukaryotic mRNAs IsPromoter Proximal Pausing of RNA Polymerase Regulated 440
Occurs in Some Rapidly Induced Genes 409Translation of Some mRNAs Is Regulated by Specifi c
11 .2 Processing of Eukaryotic mRNA 410
RNA-Binding Proteins 44 2
The 5 ' -Cap Is Added to Nascent RNAs Shortly after
Antisense RNA Regulates Translation of Transposase
Initiation by RNA Polymerase II 410
mRNA in Bacteria 44 2
Pre-mRNAs Are Associated with hnRNP Protein sContaining Conserved RNA-Binding Domains 410
11.6 Processing of rRNA and tRNA 44 3
hnRNP Proteins May Assist in Processing and Transport
Pre-rRNA Genes Are Similar in All Eukaryotes an d
of mRNAs 413
Function as Nucleolar Organizers 44 3
Pre-mRNAs Are Cleaved at Specific 3' Sites and Rapidly
Small Nucleolar RNAs (snoRNAs) Assist in Processin g
Polyadenylated 413
rRNAs and Assembling Ribosome Subunits 44 4
Splicing Occurs at Short, Conserved Sequences in Pre-
Self-Splicing Group I Introns Were the First Examples o f
mRNAs via Two Transesterification Reactions 415
Catalytic RNA 445
Spliceosomes, Assembled from snRNPs and a Pre-
All Pre-tRNAs Undergo Cleavage and Base
mRNA, Carry Out Splicing 416
Modification 446
Splicing of Pre-tRNAs Differs from Other Splicing
DNA Damage Can Be Repaired by Severa lMechanisms 448
Mechanisms 47 5
MEDIA CONNECTIONS
Eukaryotes Have DNA-Repair Systems Analogous t o
Overview: Life Cycle of an mRNA
Those of E. colt 479
Focus: mRNA Splicing
Inducible DNA-Repair Systems Are Error-Prone 48 1
Classic Experiment 11 .1 : Catalysis without
12.5 Recombination between Homologous DNAProteins: The Discovery of Self-Splicing RNA
Sites 482The Crossed-Strand Holliday Structure Is a n
Intermediate in Recombination 48 2
12 DNA Replication, Repair,
Double-Strand Breaks in DNA Initiat eRecombination 484and Recombination
The Activities of E. coil Recombination Proteins Have12 .1 General Features of Chromosomal
Been Determined 486Replication 454
Cre Protein and Other Recombinases Catalyze Site-DNA Replication Is Semiconservative 454
Specific Recombination 48 8
Most DNA Replication Is Bidirectional 455
MEDIA CONNECTION SDNA Replication Begins at Specific Chromosomal
Focus: Bidirectional Replication of DN ASites 456
Focus: Nucleotide Polymerization by DN APolymerase
12.2 The DNA Replication Machinery 458
Focus: Coordination of Leading and Laggin gDnaA Protein Initiates Replication in E. coli 459
Strand Synthesis
DnaB Is an E . colt Helicase That Melts Duplex
Focus: Telomere Replicatio nDNA 460
Classic Experiment 12 .1: Proving That DNAE. coli Primase Catalyzes Formation of RNA Primers for
Replication Is SemiconservativeDNA Synthesis 46 0
At a Growing Fork One Strand Is Synthesize dDiscontinuously from Multiple Primers 46 1
E. colt DNA Polymerase III Catalyzes Nucleotide
13 Regulation of the EukaryoticAddition at the Growing Fork 462
Cell CycleThe Leading and Lagging Strands Are Synthesized
Concurrently 463
13 .1 Overview of the Cell Cycle and Its Control 496
Eukaryotic Replication Machinery Is Generally Similar
The Cell Cycle Is an Ordered Series of Events Leading t o
to That of E. colt 464
Replication of Cells 496
Telomerase Prevents Progressive Shortening of Lagging
Regulated Protein Phosphorylation and Degradatio n
Strands during Eukaryotic DNA Replication 467
Control Passage through the Cell Cycle Diverse 49 6
Diverse Experimental Systems Have Been Used t o
12 .3 The Role of Topoisomerases in DNA
Identify and Isolate Cell-Cycle Control Proteins 49 8
Replication 468
13 .2 Biochemical Studies with Oocytes, Eggs, and Earl yType I Topoisomerases Relax DNA by Nicking and Then
Embryos 500Closing One Strand of Duplex DNA 468
MPF Promotes Maturation of Oocytes and Mitosis i nType II Topoisomerases Change DNA Topology by
Somatic Cells 500Breaking and Rejoining Double Stranded DNA 469
Mitotic Cyclin Was First Identified in Early Sea Urchi nReplicated Circular DNA Molecules Are Separated by
Embryos 50 1Type II Topoisomerases 470
Cyclin B Levels and MPF Activity Change in CyclingLinear Daughter Chromatids Also Are Separated by
Xenopus Egg Extracts 50 2Type II Topoisomerases 471
Ubiquitin-Mediated Degradation of Mitotic Cyclin sPromotes Exit from Mitosis 50 3
12 .4 DNA Damage and Repair and Their Role in
Regulation of APC Activity Controls Degradation o fCarcinogenesis 472
Cyclin B 504Proofreading by DNA Polymerase Corrects Copying
Errors 472
13 .3 Genetic Studies with S . pombe 506
Chemical Carcinogens React with DNA Directly or after
Two Classes of Mutations in S. pombe Produce Eithe rActivation 474
Elongated or Very Small Cells 50 6
The Carcinogenic Effect of Chemicals Correlates with
S. pombe Cdc2-Cdc13 Heterodimer Is Equivalent t oTheir Mutagenicity 475
Xenopus MPF 506
Phosphorylation of the Catalytic Subunit Regulates MPF
Classic Experiment 13 .1: Cell Biology EmergingKinase Activity 507
from the sea: The Discovery of Cyclin s
Conformational Changes Induced by Cyclin Binding andPhosphorylation Increase MPF Activity 50 8
Other Mechanisms Also Control Entry into Mitosis b yRegulating MPF Activity 509
14 Gene Control in Development
13.4 Molecular Mechanisms for Regulating Mitotic
14 .1 Cell-Type Specification and Mating-Type
Events 510
Conversion in Yeast 53 8
Phosphorylation of Nuclear Lamins by MPF Leads to
Combinations of DNA-Binding Proteins Regulate Cell -
Nuclear-Envelope Breakdown 510
Type Specification in Yeast 53 8
Mating of a and a Cells Is Induced by Pheromone -Other Early Mitotic Events May Be Controlled Directly
Stimulated Gene Expression 54 0or Indirectly by MPF 512Multiple Regulation of HO Transcription ControlsAPC-Dependent Unlinking of Sister Chromatids Initiates
Mating Type Conversion 54 1Anaphase 513Silencer Elements Repress Expression at HML and
Phosphatase Activity Is Required for Reassembly of the
HMR 542Nuclear Envelope and Cytokinesis 51 4
13.5 Genetic Studies with S. cerevisiae 517
14 .2 Cell-Type Specification in Animals 54 3S . cerevisiae Cdc28 Is Functionally Equivalent to
Embryonic Somites Give Rise to Myoblasts, th eS. pombe Cdc2 518
Precursors of Skeletal Muscle Cells 54 3
Three G I Cyclins Associate with Cdc238 to Form
Myogenic Genes Were First Identified in Studies with
S Phase-Promoting Factors 519
Cultured Fibroblasts 544
Kinase Activity of Cdc28-G, Cyclin Complexes Prepares
Myogenic Proteins Are Transcription Factors Containing
Cells for the S Phase 519
a Common bHLH Domain 546
Degradation of the S-Phase Inhibitor Sicl Triggers DNA
MEFs Function in Concert with MRFs to Confe r
Replication 520
Myogenic Specificity 546
Multiple Cyclins Direct Kinase Activity of Cdc28 during
Myogenic Stages at Which MRFs and MEFs Function i n
Different Cell-Cycle Phases 522
Vivo Have Been Identified 547
Replication at Each Origin Is Initiated Only Once during
Multiple MRFs Exhibit Functional Diversity and Permi t
the Cell Cycle 522
Flexibility in Regulating Development 54 8
Terminal Differentiation of Myoblasts Is under Positiv e
13.6 Cell-Cycle Control in Mammalian Cells 524
and Negative Control 549
Mammalian Restriction Point Is Analogous to START in
A Network of Cross-Regulatory Interactions Maintain sYeast Cells 524
the Myogenic Program 549
Multiple Cdks and Cyclins Regulate Passage of
Neurogenesis Requires Regulatory Proteins Analogous t oMammalian Cells through the Cell Cycle 524
bHLH Myogenic Proteins 55 0
Regulated Expression of Two Classes of Genes Returns
Progressive Restriction of Neural Potential Require s
Go Mammalian Cells to the Cell Cycle 526
Inhibitory HLH Proteins and Local Cell-Cel l
Passage through the Restriction Point Depends on
Interactions 55 1
Activation of E2F Transcription Factors 526
bHLH Regulatory Circuitry May Operate to Specify
Cyclin A Is Required for DNA Synthesis and Cdk1 for
Other Cell Types 55 2
Entry into Mitosis 52 8
Mammalian Cyclin-Kinase Inhibitors Contribute to Cell-
14.3 Anteroposterior Specification duringCycle Control 528
Embryogenesis 553Drosophila Has Two Life Forms 554
13.7 Checkpoints in Cell-Cycle Regulation 529
Patterning Information Is Generated during Oogenesi sThe Presence of Unreplicated DNA Prevents Entry into
and Early Embryogenesis 55 5Mitosis 530
Four Maternal Gene Systems Control Early Patterning i n
Improper Assembly of the Mitotic Spindle Leads to
Fly Embryos 55 6Arrest in Anaphase 530
Morphogens Regulate Development as a Function of
G I and G2 Arrest in Cells with Damaged DNA Depends
Their Concentration 55 6on a Tumor Suppressor and Cyclin-Kinase
Maternal bicoid Gene Specifies Anterior Region inInhibitor 531
Drosophila 55 7
MEDIA CONNECTIONS
Maternally Derived Inhibitors of Translation Contribut e
Overview: Cell Cycle Control
to Early Drosophila Patterning 558
Graded Expression of Several Gap Genes Further
Muscle Ca t+ ATPase Pumps Ca t+ Ions from the Cytoso lSubdivides Fly Embryo into Unique Spatial
into the Sarcoplasmic Reticulum 59 1Domains 560
Na + /K + ATPase Maintains the Intracellular Na ' and K +Expression of Three Groups of Zygotic Genes
Concentrations in Animal Cells 59 3Completes Early Patterning in Drosophila 560
V-Class H + ATPases Pump Protons across Lysosoma lSelector (Hox) Genes Occur in Clusters in the
and Vacuolar Membranes 594Genome 563
The ABC Superfamily Transports a Wide Variety o fCombinations of Different Hox Proteins Contribute to
Substrates 59 5Specifying Parasegment Identity in Drosophila 565
15 .6 Cotransport by Symporters and Antiporters 59 7Specificity of Drosophila Hox-Protein Function IsMediated by Exd Protein 566
Na + -Linked Symporters Import Amino Acids an dGlucose into Many Animal Cells 59 8
Hox-Gene Expression Is Maintained by Autoregulation
+
2 +and Changes in Chromatin Structure 567
Na Linked Antiporter Exports Ca from Cardia c
Mammalian Homologs of Drosophila ANT-C and BX-C
Muscle Cells 598
Genes Occur in Four Hox Complexes 568
AEI Protein, a Cl -1HC0 3 - Antiporter, Is Crucial toCO 2 Transport by Erythrocytes 59 9
Mutations in Hox Genes Result in Homeoti cTransformations in the Developing Mouse 569
Several Cotransporters Regulate Cytosolic pH 600
Numerous Transport Proteins Enable Plant Vacuoles t o14.4 Specification of Floral-Organ Identity in
Accumulate Metabolites and Ions 60 1Arabidopsis 571
15 .7 Transport across Epithelia 602Flowers Contain Four Different Organs 571
The Intestinal Epithelium Is Highly Polarized 60 2Three Classes of Genes Control Floral-Orga nIdentity 572
Transepithelial Movement of Glucose and Amino Acid sRequires Multiple Transport Proteins 602Many Floral Organ-Identity Genes Encode MADS
Parietal Cells Acidify the Stomach Contents Whil eFamily Transcription Factors 573Maintaining a Neutral Cytosolic pH 60 4
MEDIA CONNECTIONS
Tight Junctions Seal Off Body Cavities and Restric tOverview: Gene Control In Embryonic
Diffusion of Membrane Components 60 4Development
Classic Experiment 14 .1 : Using Lethal Injection to
Other Junctions Interconnect Epithelial Cells an d
Study Development
Control Passage of Molecules between Them 60 7
15 .8 Osmosis, Water Channels, and the Regulation o f
PART III : Building and Fueling the Cell
Cell Volume 60 8Osmotic Pressure Causes Water to Move across
Membranes 60 8
15 Transport across Cell Membranes
Different Cells Have Various Mechanisms fo rControlling Cell Volume 60 9
15 .1 Diffusion of Small Molecules across Phospholipid
Water Channels Are Necessary for Bulk Flow of Wate rBilayers 579
across Cell Membranes 61 0
15 .2 Overview of Membrane Transport Proteins 580
Simple Rehydration Therapy Depends on Osmoti cGradient Created by Absorption of Glucose and
15.3 Uniporter-Catalyzed Transport 582
Na' 610Three Main Features Distinguish Uniport Transport from
Changes in Intracellular Osmotic Pressure Cause Lea fPassive Diffusion 582
Stomata to Open 61 1GLUT1 Transports Glucose into Most Mammalia n
Cells 583
MEDIA CONNECTION S
Overview: Biological Energy Intercom ersion s15 .4 Intracellular Ion Environment and Membrane
Classic Experiment 15 .1: Stumbling upon ActiveElectric Potential 585
Transpor t
Ionic Gradients and an Electric Potential Are Maintaine dacross the Plasma Membrane 585
16 Cellular Energetics: Glycolysis,The Membrane Potential in Animal Cells Depends
Aerobic Oxidation, andLargely on Resting K + Channels 58 6
Na' Entry into Mammalian Cells Has a Negative AG
Photosynthesis587
16.1 Oxidation of Glucose and Fatty Acids to CO 2 61 815 .5 Active Transport by ATP-Powered Pumps 588
Cytosolic Enzymes Convert Glucose to Pyruvate 61 9
Plasma-Membrane Ca t+ ATPase Exports Ca t+ Ions
Substrate-Level Phosphorylation Generates ATP durin gfrom Cells 591
Glycolysis 619
Anaerobic Metabolism of Each Glucose Molecule Yields
Chlorophyll a Is Present in Both Components of aOnly Two ATP Molecules 619
Photosystem 65 1Mitochondria Possess Two Structurally and Functionally
Light Absorption by Reaction-Center Chlorophyll sDistinct Membranes 622
Causes a Charge Separation across the Thylakoi dMitochondrial Oxidation of Pyruvate Begins with the
Membrane 652Formation of Acetyl CoA 623
Light-Harvesting Complexes Increase the Efficiency o fOxidation of the Acetyl Group of Acetyl CoA in the
Photosynthesis 653Citric Acid Cycle Yields CO 2 and Reduced
16.4 Molecular Analysis of Photosystems 65 5Coenzymes 62 5
Inner-Membrane Proteins Allow the Uptake of Electrons
Photoelectron Transport in Purple Bacteria Produces a
from Cytosolic NADH 626
Charge Separation 65 5
Mitochondrial Oxidation of Fatty Acids Is Coupled to
Both Cyclic and Noncyclic Electron Transport Occur in
ATP Formation 627
Bacterial Photosynthesis 65 6
Oxidation of Fatty Acids in Peroxisomes Generates No
Chloroplasts Contain Two Functionally and Spatiall y
ATP 629
Distinct Photosystems 65 8
The Rate of Glucose Oxidation Is Adjusted to Meet the
An Oxygen-Evolving Complex in PSII Regenerate s
Cell's Need for ATP 630
P 680 65 9
Cyclic Electron Flow in PSI Generates ATP but N o
16.2 Electron Transport and Oxidative
NADPH 66 1
Phosphorylation 632
PSI and PSII Are Functionally Coupled 66 1
The Proton Motive Force in Mitochondria Is Due
Both Plant Photosystems Are Essential for Formation o f
Largely to a Voltage Gradient across the Inner
NADPH and 02 66 2
Membrane 633
16.5 CO 2 Metabolism during Photosynthesis 66 4Electron Transport in Mitochondria Is Coupled to
CO 2 Fixation Occurs in the Chloroplast Stroma 664Proton Translocation 634
Synthesis of Sucrose Incorporating Fixed CO2 I sElectrons Flow from FADH2 and NADH to 02 via a
Completed in the Cytosol 66 5Series of Multiprotein Complexes 634
Light Stimulates CO 2 Fixation by Severa lCoQ and Cytochrome c Shuttle Electrons from One
Mechanisms 66 7Electron Transport Complex to Another 639
Photorespiration, Which Consumes CO2 and Liberate sReduction Potentials of Electron Carriers Favor Electron
CO 2 , Competes with Photosynthesis 667Flow from NADH to 02 639
The C4 Pathway for CO2 Fixation Is Used by Man yCoQ and Three Electron Transport Complexes Pump
Tropical Plants 66 7Protons out of the Mitochondrial Matrix 639
Sucrose Is Transported from Leaves through the PhloemExperiments with Membrane Vesicles Support the
to All Plant Tissues 67 0Chemiosmotic Mechanism of ATP Formation 64 1
Bacterial Plasma-Membrane Proteins Catalyze Electron
MEDIA CONNECTIONS
Transport and Coupled ATP Synthesis 643
Focus: Electron Transport
ATP Synthase Comprises a Proton Channel (Fo) and
Focus: Photosynthesi s
ATPase (F l ) 643
Focus: ATP Synthesis
The FoF l Complex Harnesses the Proton-Motive Forc eto Power ATP Synthesis 64 5
Transporters in the Inner Mitochondrial Membrane Are
17 Protein Sorting: OrganellePowered by the Proton-Motive Force 64 6
Rate of Mitochondrial Oxidation Normally Depends on
Biogenesis and Protein Secretion
ADP Levels 647
17.1 Synthesis and Targeting of Mitochondrial andBrown-Fat Mitochondria Contain an Uncoupler of
Chloroplast Proteins 677Oxidative Phosphorylation 647
Most Mitochondrial Proteins Are Synthesized a sCytosolic Precursors Containing Uptake-Targeting
16.3 Photosynthetic Stages and Light-Absorbing
Sequences 677Pigments 648
Cytosolic Chaperones Deliver Proteins to Channel-Photosynthesis Occurs on Thylakoid Membranes 649
Linked Receptors in the Mitochondria l
Three of the Four Stages in Photosynthesis Occur Only
Membrane 679
during Illumination 649
Matrix Chaperones and Chaperonins Are Essential fo r
Each Photon of Light Has a Defined Amount of
the Import and Folding of Mitochondria l
Energy 651
Proteins 680
Studies with Chimeric Proteins Confirm Major Features
Correct Folding of Newly Made Proteins Is Facilitate dof Mitochondrial Import 682
by Several ER Proteins 70 8The Uptake of Mitochondrial Proteins Requires
Assembly of Subunits into Multimeric Proteins Occurs i nEnergy 682
the ER 709Proteins Are Targeted to Submitochondrial
Only Properly Folded Proteins Are Transported from th eCompartments by Multiple Signals and Several
Rough ER to the Golgi Complex 71 0Pathways 684
Many Unassembled or Misfolded Proteins in the ER Ar eThe Synthesis of Mitochondrial Proteins Is
Transported to the Cytosol and Degraded 71 1Coordinated 685
ER-Resident Proteins Often Are Retrieved from the Cis -Several Uptake-Targeting Sequences Direct Proteins
Golgi 71 1Synthesized in the Cytosol to the Appropriat eChloroplast Compartment 685
17.7 Protein Glycosylation in the ER and Golg i
17 .2 Synthesis and Targeting of Peroxisomal
Complex 71 2
Proteins 689
Different Structures Characterize N- and 0-Linke d
C- and N-Terminal Targeting Sequences Direct Entry of
Oligosaccharides 71 2
Folded Proteins into the Peroxisomal Matrix 689
0-Linked Oligosaccharides Are Formed by th e
Peroxisomal Protein Import Is Defective in Some Genetic
Sequential Transfer of Sugars from Nucleotide
Diseases 690
Precursors 71 2
ABO Blood Type Is Determined by Two17.3 Overview of the Secretory Pathway 691
Glycosyltransferases 71 5Secretory Proteins Move from the Rough ER Lumen
A Common Preformed N-Linked Oligosaccharide I sthrough the Golgi Complex and Then to the Cell
Added to Many Proteins in the Rough ER 71 6Surface 692
Modifications to N-Linked Oligosaccharides Ar eAnalysis of Yeast Mutants Defined Major Steps in the
Completed in the Golgi Complex 71 8Secretory Pathway 694
Oligosaccharides May Promote Folding and Stability o fAnterograde Transport through the Golgi Occurs by
Glycoproteins 71 9Cisternal Progression 695
Mannose 6-Phosphate Residues Target Proteins toPlasma-Membrane Glycoproteins Mature via the Same
Lysosomes 71 9Pathway as Continuously Secreted Proteins 695
Lysosomal Storage Diseases Provided Clues to Sorting o f
17.4 Translocation of Secretory Proteins across the ER
Lysosomal Enzymes 72 0
Membrane 69 6A Signal Sequence on Nascent Secretory Proteins Targets
17.8 Golgi and Post Golgi Protein Sorting an d
Them to the ER and Is Then Cleaved Off 696
Proteolytic Processing 72 2
Two Proteins Initiate the Interaction of Signal Sequences
Sequences in the Membrane-Spanning Domain Cause th e
with the ER Membrane 697
Retention of Proteins in the Golgi 72 2
Polypeptides Move through the Translocon into the ER
Different Vesicles Are Used for Continuous an d
Lumen 699
Regulated Protein Secretion 72 3
GTP Hydrolysis Powers Protein Transport into the ER in
Proproteins Undergo Proteolytic Processing Late i n
Mammalian Cells 700
Maturation 72 3
.5 Insertion of Membrane Proteins into the ER
Some Proteins Are Sorted from the Golgi Complex t o17 .5
Apical or Basolateral Plasma Membrane 72 4Membrane 70 2Most Nominal Cytosolic Transmembrane Proteins Have
17 .9 Receptor-Mediated Endocytosis and the Sorting o fan N-Terminal Signal Sequence and Internal
Internalized Proteins 72 7Topogenic Sequence 702
The LDL Receptor Binds and Internalizes Cholesterol -A Single Internal Topogenic Sequence Directs Insertion
Containing Particles 72 8of Some Single Pass Transmembrane Proteins 704
Cytosolic Sequences in Some Cell-Surface ReceptorsMultipass Transmembrane Proteins Have Multiple
Target Them for Endocytosis 72 8Topogenic Sequences 70 5
After Insertion in the ER Membrane, Some Proteins Are
The Acidic pH of Late Endosomes Causes Mos tReceptors and Ligands to Dissociate 72 9
Transferred to a GPI Anchor 705
The Endocytic Pathway Delivers Transferrin-Bound Iro n
17.6 Post-Translational Modifications and Quality
to Cells 73 1
Control in the Rough ER 707
Some Endocytosed Proteins Remain within the
Disulfide Bonds Are Formed and Rearranged in the ER
Cell 73 1
Lumen 707
Transcytosis Moves Some Ligands across Cells 732
17.10 Molecular Mechanisms of Vesicular
18 .3 Myosin: The Actin Motor Protein 76 9
Traffic 733
All Myosins Have Head, Neck, and Tail Domains with
At Least Three Types of Coated Vesicles Transport
Distinct Functions 76 9
Proteins from Organelle to Organelle 733
Myosin Heads Walk along Actin Filaments 77 0
Clathrin Vesicles Mediate Several Types of Intracellular
Myosin Heads Move in Discrete Steps, Each Coupled toTransport 733
Hydrolysis of One ATP 77 1
COP I Vesicles Mediate Retrograde Transport within the
Myosin and Kinesin Share the Ras Fold with Certai nGolgi and from the Golgi Back to the ER 738
Signaling Proteins 77 1COP II Vesicles Mediate Transport from the ER to the
Conformational Changes in the Myosin Head CoupleGolgi 741
ATP Hydrolysis to Movement 773
Specific Fusion of Intracellular Vesicles Involves aConserved Set of Fusion Proteins 741
18.4 Muscle : A Specialized Contractile Machine 77 4Conformational Changes in Influenza HA Protein
Some Muscles Contract, Others Generate Tension 775Trigger Membrane Fusion 743
Skeletal Muscles Contain a Regular Array of Actin andMEDIA CONNECTIONS
Myosin 775Overview: Protein Sorting
Smooth Muscles Contain Loosely Organized Thick an dOverview: Protein Secretion
Thin Filaments 777Focus: Synthesis of Secreted and Membrane-
Thick and Thin Filaments Slide Past One Another durin gBound Proteins
Contraction 777Classic Experiment 17 .1: Following a Protein out
Titin and Nebulin Filaments Organize th eof the Cell
Sarcomere 77 8
A Rise in Cytosolic Ca" Triggers Muscle
18 Cell Motility and Shape I:
Contraction 779
Actin-Binding Proteins Regulate Contraction in Bot hMicrofilaments
Skeletal and Smooth Muscle 780
Myosin-Dependent Mechanisms Also Contro l18.1 The Actin Cytoskeleton 752
Contraction in Some Muscles 78 1Eukaryotic Cells Contain Abundant Amounts of Highly
Conserved Actin 753
18.5 Actin and Myosin in Nonmuscle Cells 783ATP Holds Together the Two Lobes of the Actin
Actin and Myosin II Are Arranged in Contractil eMonomer 753
Bundles That Function in Cell Adhesion 78 3G -Actin Assembles into Long, Helical F-Actin
Myosin II Stiffens Cortical Membranes 78 4Polymers 754
Actin and Myosin II Have Essential Roles inF-Actin Has Structural and Functional Polarity 754
Cytokinesis 78 4The Actin Cytoskeleton Is Organized into Bundles and
Membrane-Bound Myosins Power Movement of SomeNetworks of Filaments 755
Vesicles 785Cortical Actin Networks Are Connected to th e
Membrane 756
Actin Bundles Support Projecting Fingers of
18 .6 Cell Locomotion 78 7
Membrane 760
Controlled Polymerization and Rearrangements of Acti nFilaments Occur during Keratinocyte Movement 78 7
18.2 The Dynamics of Actin Assembly 761
Ameboid Movement Involves Reversible Gel-SolActin Polymerization In Vitro Proceeds in Three
Transitions of Actin Networks 78 9Steps 761
Myosin I and Myosin II Have Important Roles in Cel l
Actin Filaments Grow Faster at One End Than at the
Migration 78 9Other 761
Migration of Cells Is Coordinated by Various Secon dToxins Disrupt the Monomer-Polymer Equilibrium 763
Messengers and Signal-Transductio n
Actin Polymerization Is Regulated by Proteins That Bind
Pathways 790
G-Actin 763
MEDIA CONNECTION SSome Proteins Control the Lengths of Actin Filaments by
Focus: Actin PolymerizationSevering Them 765
Technique: In Vitro Motility AssayActin Filaments Are Stabilized by Actin-Capping
Focus: Myosin Crossbridge CycleProteins 765
Overview: Cell Motilit yMany Movements Are Driven by Actin
Classic Experiment 18 .1: Looking at MusclePolymerization 766
Contraction
Axonemal Dyneins Are Multiheaded Motor19 Cell Motility and Shape II :
Proteins 820
Microtubules and Intermediate
Conversion of Microtubule Sliding into Axonema l
Filaments
Bending Depends on Inner-Arm Dyneins 82 1
Proteins Associated with Radial Spokes May Contro l19.1 Microtubule Structures 796
Flagellar Beat 82 1
Heterodimeric Tubulin Subunits Compose the Wall of a
Axonemal Microtubules Are Dynamic and Stable 82 2Microtubule 79 6
Microtubules Form a Diverse Array of Both Permanent
19.5 Microtubule Dynamics and Motor Proteins durin gand Transient Structures 797
Mitosis 823Microtubules Assemble from Organizing
The Mitotic Apparatus Is a Microtubule Machine fo rCenters 799
Separating Chromosomes 823Most Microtubules Have a Constant Orientation
The Kinetochore Is a Specialized Attachment Site at theRelative to MTOCs 800
Chromosome Centromere 82 5The y-Tubulin Ring Complex Nucleates Polymerization
Centrosome Duplication Precedes and Is Required forof Tubulin Subunits 800
Mitosis 827
Dynamic Instability of Microtubules Increases during19.2 Microtubule Dynamics and Associated
Mitosis 82 8Proteins 802
Organization of the Spindle Poles Orients the Assembl yMicrotubule Assembly and Disassembly Occur
of the Mitotic Apparatus 82 9Preferentially at the (+) End 802
Formation of Poles and Capture of Chromosomes Ar eDynamic Instability Is an Intrinsic Property of
Key Events in Spindle Assembly 82 9Microtubules 805
Kinetochores Generate the Force for PolewardColchicine and Other Drugs Disrupt Microtubule
Chromosome Movement 83 1Dynamics 806
During Anaphase Chromosomes Separate and th eAssembly MAPs Cross-Link Microtubules to One
Spindle Elongates 83 2Another and Other Structures 807
Astral Microtubules Determine Where Cytokinesis Take sBound MAPs Alter Microtubule Dynamics 809
Place 83 3
Plant Cells Reorganize Their Microtubules and Build a19.3 Kinesin, Dynein, and Intracellular Transport 809
New Cell Wall during Mitosis 834Fast Axonal Transport Occurs along Microtubules 80 9
Microtubules Provide Tracks for the Movement of
19.6 Intermediate Filaments 836Pigment Granules 811
Functions and Structure of Intermediate FilamentsIntracellular Membrane Vesicles Travel along
Distinguish Them from Other Cytoskeleta lMicrotubules 812
Fibers 836Kinesin Is a (+) End-Directed Microtubule Motor
IF Proteins Are Classified into Six Types 83 7Protein 812
Intermediate Filaments Can Identify the Cellular OriginEach Member of the Kinesin Family Transports a
of Certain Tumors 83 8Specific Cargo 815
All IF Proteins Have a Conserved Core Domain and AreDynein Is a (-) End-Directed Microtubule Motor
Organized Similarly into Filaments 83 8Protein 815
Intermediate Filaments Are Dynamic Polymers in th eDynein-Associated MBPs Tether Cargo to
Cell 840Microtubules 816
Various Proteins Cross-Link Intermediate Filaments an dMultiple Motor Proteins Are Associated with Membrane
Connect Them to Other Cell Structures 84 0Vesicles 816
IF Networks Support Cellular Membranes 84 0
19.4 Cilia and Flagella : Structure and
Intermediate Filaments Are Anchored in Cel lJunctions 842
Movement 817
Desmin and Associated Proteins Stabilize Sarcomeres inAll Eukaryotic Cilia and Flagella Contain Bundles of
Muscle 842Doublet Microtubules 817
Disruption of Keratin Networks Causes Blistering 84 3Ciliary and Flagellar Beating Are Produced by
Controlled Sliding of Outer Doublet
MEDIA CONNECTIONS
Microtubules 820
Focus: Mitosis
Dynein Arms Generate the Sliding Forces in
Focus: Microtubule Dynamics
Axonemes 820
Classic Experiment 19 .1: Racing Down the Axon
PART IV: Cell Interactions
Gio, and Gs , Interact with Different Regions of Adenyly lCyclase 87 1
Degradation of cAMP Also Is Regulated 87 1
20 Cell-to-Cell Signaling :
20.4 Receptor Tyrosine Kinases and Ras 87 1
Hormones and Receptors
Ligand Binding Leads to Autophosphorylation o fRTKs 872
20.1 Overview of Extracellular Signaling 849
Ras and G s , Subunits Belong to the GTPase Superfamil ySignaling Molecules Operate over Various Distances in
of Intracellular Switch Proteins 872Animals 849
An Adapter Protein and GEF Link Most Activated RTK sReceptor Proteins Exhibit Ligand-Binding and Effector
to Ras 87 3Specificity 850
SH2 Domain in GRB2 Adapter Protein Binds to aHormones Can Be Classified Based on Their Solubility
Specific Phosphotyrosine in an Activatedand Receptor Location 850
RTK 876
Cell-Surface Receptors Can Belong to Four Major
Sos, a Guanine-Nucleotide-Exchange Factor, Binds toClasses 852
the SH3 Domains in GRB2 87 7
Effects of Many Hormones Are Mediated by Secon dMessengers 854
20.5 MAP Kinase Pathways 878
Other Conserved Proteins Function in Signal
Signals Pass from Activated Ras to a Cascade of Protei nTransduction 854
Kinases 87 8
Common Signaling Pathways Are Initiated by Different
Ksr May Function as a Scaffold for the MAP KinaseReceptors in a Class 856
Cascade Linked to Ras 87 9
The Synthesis, Release, and Degradation of Hormones
Phosphorylation of a Tyrosine and a Threonine Activate sAre Regulated 856
MAP Kinase 88 0
Various Types of Receptors Transmit Signals to MA P20.2 Identification and Purification of Cell-Surface
Kinase 88 1
Receptors 858
Multiple MAP Kinase Pathways Are Found i n
Hormone Receptors Are Detected by Binding
Eukaryotic Cells 882Assays 859
Specificity of MAP Kinase Pathways Depends on Severa l
KD Values for Cell-Surface Hormone Receptors
Mechanisms 88 3Approximate the Concentrations of CirculatingHormones 860
20.6 Second Messengers 88 4Affinity Techniques Permit Purification of Receptor
cAMP and Other Second Messengers Activate SpecificProteins 860
Protein Kinases 884
Many Receptors Can Be Cloned without Prior
cAPKs Activated by Epinephrine Stimulation Regulat ePurification 860
Glycogen Metabolism 88 5
Kinase Cascades Permit Multienzyme Regulation and20.3 G Protein-Coupled Receptors and Their
Amplify Hormone Signals 88 6Effectors 862
Cellular Responses to cAMP Vary among Different Cel l
Binding of Epinephrine to Adrenergic Receptors Induces
Types 88 7Tissue-Specific Responses 862
Anchoring Proteins Localize Effects of cAMP to Specific
Stimulation of ß-Adrenergic Receptors Leads to a Rise in
Subcellular Regions 887cAMP 863
Modification of a Common Phospholipid Precursor
Critical Features of Catecholamines and Their Receptors
Generates Several Second Messengers 88 8
Have Been Identified 863
Hormone-Induced Release of Ca Z+ from the ER I s
Trimeric Gs Protein Links ß-Adrenergic Receptors and
Mediated by IP3 889Adenylyl Cyclase 865
Opening of Ryanodine Receptors Releases Ca Z+ Stores
Some Bacterial Toxins Irreversibly Modify
in Muscle and Nerve Cells 89 1G Proteins 868
Ca2tCalmodulin Complex Mediates Many Cellula r
Adenylyl Cyclase Is Stimulated and Inhibited by
Responses 89 1
Different Receptor-Ligand Complexes 868
DAG Activates Protein Kinase C, Which Regulates Man y
GTP-Induced Changes in G 5,, Favor Its Dissociation
Other Proteins 893
from Gß, and Association with Adenylyl
Synthesis of cGMP Is Induced by Both Peptid eCyclase 869
Hormones and Nitric Oxide 893
20.7 Interaction and Regulation of Signaling
Action Potentials Are Propagated Unidirectionall yPathways 894
without Diminution 92 3
The Same RTK Can Be Linked to Different Signaling
Movements of Only a Few Na ' and K ` Ions GeneratePathways 895
the Action Potential 92 3
Multiple G Proteins Transduce Signals to Different
Myelination Increases the Rate of Impuls eEffector Proteins 895
Conduction 92 3
Gp,, Acts Directly on Some Effectors in Mammalia nCells 895
21.3 Molecular Properties of Voltage-Gated Ion
Glycogenolysis Is Promoted by Multiple Second
Channels 92 7Messengers 897
Patch Clamps Permit Measurement of Ion Movement s
Insulin Stimulation Activates MAP Kinase and Protein
through Single Channels 92 7Kinase B 897
Voltage-Gated K + Channels Have Fou r
Insulin and Glucagon Work Together to Maintain a
Subunits Each Containing Six Transmembrane a
Stable Blood Glucose Level 898
Helices 92 9
Receptors for Many Peptide Hormones Are Down-
P Segments Form the Ion-Selectivity Filter 93 0Regulated by Endocytosis 898
The S4 Transmembrane a Helix Acts as a Voltag ePhosphorylation of Cell-Surface Receptors Modulates
Sensor 93 2
Their Activity 900
Movement of One N-Terminal Segment Inactivate s
Arrestins Have Two Roles in Regulating G Protein-
Shaker K + Channel 93 2
Coupled Receptors 901
All Pore-Forming Ion Channels Are Similar in Structur eto the Shaker K + Channel 93 2
20.8 From Plasma Membrane to Nucleus 902
Voltage-Gated Channel Proteins Probably Evolved fro mCREB Links cAMP Signals to Transcription 902
a Common Ancestral Gene 93 3MAP Kinase Regulates the Activity of Man y
Transcription Factors 904
21 .4 Neurotransmitters, Synapses, and ImpulsePhosphorylation-Dependent Protein Degradation
Transmission 935Regulates NF KB 904
Many Small Molecules Transmit Impulses at Chemica lMEDIA CONNECTIONS
Synapses 935
Focus : Second Messengers in Signaling Pathways
Influx of Ca t+ Triggers Release o fOverview: Extracellular Signaling
Neurotransmitters 93 6
Focus: Expression Cloning of Receptors
Synaptic Vesicles Can Be Filled, Exocytosed, an dClassic Experiment 20 .1: The Infancy of Signal
Recycled within a Minute 93 6Transduction : DTP Stimulation of CAMP
Multiple Proteins Participate in Docking and Fusion ofSynthesis
Synaptic Vesicles 93 6Chemical Synapses Can Be Excitatory o r
Inhibitory 93 8
21 Nerve Cells
Two Classes of Neurotransmitter Receptors Operate a t
21.1 Overview of Neuron Structure and Function 912
Vastly Different Speeds 93 9
Specialized Regions of Neurons Carry Out Different
Acetylcholine and Other Transmitters Can Activat e
Functions 912
Multiple Receptors 94 0
Synapses Are Specialized Sites Where Neurons
Transmitter-Mediated Signaling Is Terminated by Severa l
Communicate with Other Cells 914
Mechanisms 94 1
Neurons Are Organized into Circuits 915
Impulses Transmitted across Chemical Synapses Can B eAmplified and Computed 942
21 .2 The Action Potential and Conduction of Electric
Impulse Transmission across Electric Synapses Is Nearl yImpulses 917
Instantaneous 94 3
The Resting Potential, Generated Mainly by Ope n"Resting" K + Channels, Is Near EK 918
21 .5 Neutotransmitter Receptors 94 4Opening and Closing of Ion Channels Cause Predictable
Opening of Acetylcholine-Gated Cation Channels Lead sChanges in the Membrane Potential 919
to Muscle Contraction 944
Membrane Depolarizations Spread Passively Only Short
All Five Subunits in the Nicotinic Acetylcholine Recepto rDistances 920
Contribute to the Ion Channel 94 5
Voltage-Gated Cation Channels Generate Action
Two Types of Glutamate-Gated Cation Channels MayPotentials 921
Function in a Type of "Cellular Memory " 946
GABA- and Glycine-Gated Cl- Channels Are Found at
22.2 Cell-Matrix Adhesion 97 6Many Inhibitory Synapses 947
Integrins Mediate Weak Cell-Matrix and Cell-Cel lCardiac Muscarinic Acetylcholine Receptors Activate a
Interactions 977G Protein That Opens K + Channels 948
Cell-Matrix Adhesion Is Modulated by Changes in theCatecholamine Receptors Induce Changes in Second-
Activity and Number of Integrins 97 7Messenger Levels That Affect Ion-Channel
De-adhesion Factors Promote Cell Migration and Ca nActivity 949
Remodel the Cell Surface 97 8A Serotonin Receptor Indirectly Modulates K + Channel
Integrin-Containing Junctions Connect Cells to th eFunction by Activating Adenylyl Cyclase 949
Substratum 97 8Some Neuropeptides Function as Both Neurotransmitters
and Hormones 950
22.3 Collagen: The Fibrous Proteins of theMatrix 979
21 .6 Sensory Transduction 951
The Basic Structural Unit of Collagen Is a TripleMechanoreceptors and Some Other Receptors Are Gated
Helix 979Cation Channels 951
Collagen Fibrils Form by Lateral Interactions of Tripl eVisual Signals Are Processed at Multiple Levels 952
Helices 980The Light-Triggered Closing of Na' Channels
Assembly of Collagen Fibers Begins in the ER and I sHyperpolarizes Rod Cells 952
Completed Outside the Cell 98 1Absorption of a Photon Triggers Isomerization of Retinal
Mutations in Collagen Reveal Aspects of Its Structur eand Activation of Opsin 953
and Biosynthesis 98 2Cyclic GMP Is a Key Transducing Molecule in Rod
Collagens Form Diverse Structures 984Cells 954
Rod Cells Adapt to Varying Levels of Ambient
22.4 Noncollagen Components of the Extracellula rLight 956
Matrix 98 5Color Vision Utilizes Three Opsin Pigments 957
Laminin and Type IV Collagen Form the Two -A Thousand Different G Protein-Coupled Receptors
Dimensional Reticulum of the Basal Lamina 986Detect Odors 958
Fibronectins Bind Many Cells to Fibrous Collagens an d
21.7 Learning and Memory 960
Other Matrix Components 98 7
Proteoglycans Consist of Multiple Glycosaminoglycan sRepeated Conditioned Stimuli Cause Decrease in Aplysia
Linked to a Core Protein 989Withdrawal Response 96 0
Facilitator Neurons Mediate Sensitization of Aplysia
Many Growth Factors Are Sequestered and Presented t o
Withdrawal Reflex 961
Cells by Proteoglycans 992
Coincidence Detectors Participate in Classical
Hyaluronan Resists Compression and Facilitates Cell
Conditioning and Sensitization 961
Migration 99 2
Long-Term Memory Requires Protein Synthesis 962
22.5 The Dynamic Plant Cell Wall 993
MEDIA CONNECTIONS
The Cell Wall Is a Laminate of Cellulos e
Overview: Biological Energy Interconversions
Fibrils in a Pectin and Hemicellulos e
Classic Experiment 21.2: Sending a Signal through
Matrix 99 3
a Gas
Cell Walls Contain Lignin and an ExtendedHydroxyproline-Rich Glycoprotein 99 5
A Plant Hormone, Auxin, Signals Cell Expansion 99 622 Integrating Cells into Tissues
Cellulose Fibrils Are Synthesized and Oriented at th e
22.1 Cell-Cell Adhesion and Communication 969
Plant Cortex 996
Plasmodesmata Directly Connect the Cytosol of AdjacentCadherins Mediate Cat+-Dependent Homophilic Cell-
Cells in Higher Plants 99 8Cell Adhesion 97 1
N-CAMs Mediate Cat+-Independent Homophilic Cell - MEDIA CONNECTION S
Cell Adhesion 971
Focus: Cell-Cell Adhesion In LeukocyteExtravasation
Selectins and Other CAMs Participate in Leukocyt eExtravasation 972
Cadherin-Containing Junctions Connect Cells to One
23 Cell Interactions in Developmen tAnother 973
Gap Junctions Allow Small Molecules to Pass between
23.1 Dorsoventral Patterning by TGFß3-SuperfamilyAdjacent Cells 974
Proteins 1004Connexin, a Transmembrane Protein, Forms Cylindrical
TGF/3 Proteins Bind to Receptors That Hav eChannels in Gap Junctions 975
Serine/Threonine Kinase Activity 1005
Activated TGFß Receptors Phosphorylate Smad
Growth Cones Navigate along Specific Axon Tracts 103 2Transcription Factors 1006
Soluble Graded Signals Can Attract and Repel Growt hDpp Protein, a TGFß Homolog, Controls Dorsoventral
Cones 1034Patterning in Drosophila Embryos 1007
23 .6 Directional Control of Neurona lSequential Inductive Events Regulate Early Xenopus
Outgrowth 1034Development 1007
Three Genes Control Dorsoventral Outgrowth o fInductive Effect of TGFß Homologs Is Regulated Post-
Neurons in C. elegans 103 4Translationally 1009
Vertebrate Homologs of C. elegans UNC-6 Both AttractA Highly Conserved Pathway Determines Dorsoventral
and Repel Growth Cones 103 4Patterning in Invertebrates and Vertebrates 1012
UNC-40 Mediates Chemoattraction in Response t o
23 .2 Tissue Patterning by Hedgehog and
Netrin in Vertebrates 103 6
Wingless 1013
UNC-5 and UNC-40 Together Mediate Chemorepulsio n
Modification of Secreted Hedgehog Precursor Yields a
in Response to Netrin 103 6
Cell-Tethered Inductive Signal 1013
Prior Experience Modulates Growth-Cone Response t o
Binding of Hedgehog to the Patch Receptor Relieves
Netrin 1037
Inhibition of Smo 1014
Other Signaling Systems Can Both Attract and Repe l
Hedgehog Organizes Pattern in the Chick Limb and
Growth Cones 103 8
Drosophila Wing 1014
23 .7 Formation of Topographic Maps andHedgehog Induces Wingless, Which Triggers a Highly
Synapses 1039Conserved Signaling Pathway 1017
Visual Stimuli Are Mapped onto the Tectum 103 9
23.3 Molecular Mechanisms of Responses to
Temporal Retinal Axons Are Repelled by Posterio rTectal Membranes 1039
Morphogens 1018
Ephrin A Ligands Are Expressed as a Gradient along th eHedgehog Gradient Elicits Different Cell Fates in the
Anteroposterior Tectal Axis 103 9Vertebrate Neural Tube 1019
The EphA3 Receptor is Expressed in a Nasal-Tempora lCells Can Detect the Number of Ligand-Occupied
Gradient in the Retina 104 1Receptors 1019
Motor Neurons Induce Assembly of the Neuromuscula rTarget Genes That Respond Differentially to
Junction 1041Morphogens Have Different Control Regions 1019
23.8 Cell Death and Its Regulation 104 423.4 Reciprocal and Lateral Inductive
Programmed Cell Death Occurs throug hInteractions 1021
Apoptosis 104 5
Reciprocal Epithelial-Mesenchymal Interactions Regulate
Neutrophins Promote Survival of Neurons 104 5Kidney Development 1022
Three Classes of Proteins Function in the Apoptoti cActivation of the Ret Receptor Promotes Growth and
Pathway 104 6Branching of the Ureteric Bud 1023
Pro-Apoptotic Regulators Promote CaspaseThe Basal Lamina Is Essential for Differentiation of
Activation 104 8Many Epithelial Cells 1024
Some Trophic Factors Prevent Apoptosis by InducingCell-Surface Ephrin Ligands and Receptors Mediate
Inactivation of a Pro-Apoptotic Regulator 104 8Reciprocal Induction during Angiogenesis 1024
MEDIA CONNECTION SThe Conserved Notch Pathway Mediates Lateral Focus: TGFß Signaling Pathway
Interactions 1025 Focus: Apoptosi sInteractions between Two Equivalent Cells Give Rise to
Classic Experiment 23.1 : Hunting Down GenesAC and VU Cells in C. elegans 1025
Involved in Cell DeathNeuronal Developemnt in Drosophila and Vertebrates
Depends on Lateral Interactions 1027
24 Cancer
23.5 Overview of Neuronal Outgrowth 1028
24.1 Tumor Cells and the Onset of Cancer 1055
Individual Neurons Can Be Identified Reproducibly and
Metastatic Tumor Cells Are Invasive and Can
Studied 1029
Spread 1055
Growth Cones Guide the Migration and Elongation of
Alterations in Cell-to-Cell Interactions Are AssociatedDeveloping Axons 1030
with Malignancy 1056
Different Neurons Navigate along Different Outgrowth
Tumor Growth Requires Formation of New Bloo dPathways 1030
Vessels 105 6
Various Extracellular-Matrix Components Support
DNA from Tumor Cells Can Transform Norma lNeuronal Outgrowth 1031
Cultured Cells 1059
Development of a Cancer Requires Several
Inappropriate Expression of Nuclear Transcriptio nMutations 1059
Factors Can Induce Transformation 107 3
Cancers Originate in Proliferating Cells 106124.4 Mutations Causing Loss of Cell-Cycle
24.2 Proto-Oncogenes and Tumor-Suppressor
Control 1074Genes 1063
Passage from G I to S Phase Is Controlled by Proto -Gain-of-Function Mutations Convert Proto-Oncogenes
Oncogenes and Tumor-Suppressor Genes 1074into Oncogenes 1064
Loss of TGF(3 Signaling Contributes to Abnormal Cel lOncogenes Were First Identified in Cancer-Causing
Proliferation and Malignancy 107 5Retroviruses 106 5
Slow-Acting Carcinogenic Retroviruses Can Activate
24.5 Mutations Affecting Genome Stability 1076Cellular Proto-Oncogenes 1065
Mutations in p53 Abolish G I Checkpoin tMany DNA Viruses Also Contain Oncogenes 1066
Control 1076Loss-of-Function Mutations in Tumor-Suppressor Genes
Proteins Encoded by DNA Tumor Viruses Can Inhibi tAre Oncogenic 1066
p53 Activity 107 8The First Tumor-Suppressor Gene Was Identified in
Some Human Carcinogens Cause Inactivating Mutation sPatients with Inherited Retinoblastoma 1067
in the p53 Gene 1078Loss of Heterozygosity of Tumor-Suppressor Genes
Defects in DNA-Repair Systems Perpetuate Mutation sOccurs by Mitotic Recombination or Chromosome
and Are Associated with Certain Cancers 107 8Mis-Segregation 1068
Chromosomal Abnormalities Are Common in Human
24 .3 Oncogenic Mutations Affecting Cell
Tumors 107 9
Proliferation 1069
Telomerase Expression May Contribute to
Misexpressed Growth-Factor Genes Can Autostimulate
Immortalization of Cancer Cells 108 1
Cell Proliferation 1069
MEDIA CONNECTIONS
Virus-Encoded Activators of Growth Factor Receptors
Overview: Cell Cycle Contro lAct as Oncoproteins 1069
Focus: TOFF Signaling Pathway
Activating Mutations or Overexpression of Growth-
Classic Experiment 24 .1 : Studying the
Factor Receptors Can Transform Cells 1070
Transformation of Cells by DNA Tumor Viruses
Constitutively Active Signal-Transduction Proteins Ar eEncoded by Many Oncogenes 1070
Glossary G-1
Deletion of the PTEN Phosphatase Is a Frequen tOccurrence in Human Tumors 1073
Index 1-0