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Molecular Cell BiologySECOND EDITIO N
JAMES DARNEL L
HARVEY LODISH
DAVID BALTIMORE
IntroductionThe History of Molecular Cell Biology
1
PART IMolecules, Cells, Proteins, an dExperimental Techniques : A Primer
1 7
1 Chemical Foundations
1 9
2 Molecules in Cells
43
3 Synthesis of Proteins and Nuclei cAcids
8S
4 The Study of Cell Organization andSubcellular Structure
109
5 Growing and Manipulating Cells an dViruses
151
6 Manipulating Macromolecules
189
PART IIGene Expression, Structure, andReplication
227
7 RNA Synthesis and Gene Control inProkaryotes
229
8 RNA Synthesis and Processing inEukaryotes
261
9 The Structure of Eukaryotic
18 Organelle Biogenesis : The Nucleus ,Chromosomes
317
Chloroplast, and Mitochondrion
68 1
10 Eukaryotic Chromosomes and
19 Cell-to-Cell Signaling : HormonesGenes : Molecular Anatomy
347
and Receptors
709
11 Gene Control and the Molecular
20 Nerve Cells and the Electri cGenetics of Development in
Properties of Cell Membranes
76 3Eukaryotes
391
21 Microtubules and Cellular12 DNA Replication, Repair, and
Movements
81 5Recombination
449
22 Actin, Myosin, and IntermediateFilaments : Cell Movements and CellShapes
85 9
PART III
23 Multicellularity: Cell-Cell and Cell-Cell Structure and Function
489
Matrix Interactions
903
13 The Plasma Membrane
491
T14 Transport across Cell Membranes
531
PART IV15 Energy Conversion : The Formation
The New Biology : Facing Classi c
of ATP in Mitochondria and
Questions at the Frontier
953
Bacteria
583
24 Cancer
95516 Photosynthesis
617
25 Immunity
1003
17 Plasma-membrane, Secretory, and
26 Evolution of Cells
1049Lysosome Proteins : Biosynthesis an dSorting
639
Index
1077
Chapter-opening Illustrations
xxxix
IN URC)DUC"1 u 4 The History of Molecula rCell Biology
1
Evolution and the Cell Theory
2
The Theory of Evolution Arises fro mNaturalistic Studies
2
The Cell Theory Comes to Prominencethrough Improved Microscopic Technique sand Recognition That Single Cells Can Gro wand Divide
3
Classical Biochemistry and Genetics
4
Biochemistry Begins with the Demonstratio nThat Chemical Transformations Can Tak ePlace in Cell Extracts
4
Classical Genetics Begins with the Controlle dBreeding Studies of Gregor Mendel
S
Chromosomes Are Identified as the Carrier sof the Mendelian Theory of Heredity
7
The Reduction of Chromosome Numbers i nMeiosis That Forms Germ Cells Is Crucial t othe Development of the Chromosome Theoryof Heredity
7
Chromosomes Are Shown to Contain LinearArrays of Genes That Can Underg oReordering
8
The Merging of Genetics and Biochemistry
9
Acids Release Hydrogen Ions and Base s
Drosophila Studies Establish the Connection
Combine with Hydrogen Ions
29
between Gene Activity and Biochemical
Many Biological Molecules Contain Multipl eAction ; Neurospora Experiments Confirm
Acidic or Basic Groups
29That One Gene Controls One Enzyme
9
The Direction of Chemical Reactions
3 1DNA Is Identified as the Genetic Material,
The Change in Free Energy AG Determine sPaving the Way for the Study of the
the Direction of a Chemical Reaction
31Molecular Basis of Gene Structure andFunction
10
The Generation of a Concentration Gradien t
The Birth of Molecular Biology
11
Requires an Expenditure of Energy
33
Watson and Crick Deduce the Double-helical
Many Cellular Processes Involve the Transfe r
Structure of DNA
11
of Electrons in Oxidation-ReductionReactions
34X-ray Crystallography Facilitates the
An Unfavorable Chemical Reaction Ca nConstruction of Three-dimensional Models of
Proceed if It Is Coupled with an Energeticall yComplex Biological Molecules
11
Favorable Reaction
35Biochemical Experiments Have Elucidated the
Hydrolysis of the Phosphoanhydride Bonds i nRelationship between Enzymes and Metabolic
ATP Releases Substantial Free Energy
35Pathways
1 2
A Modern View of Cell Structure
12
ATP Is Used to Fuel Many Cellular Processes
37
Advances in Electron Microscopy Reveal the
Activation Energy and Reaction Rate
38
Commonality of Structures within Eukaryotic
Energy Is Required to Initiate a Reaction
39Cells
12
Enzymes Catalyze Biochemical Reactions
39Biochemical Activities Can Be Assigned to
Summary
41Specific Subcellular Structures
1 3
The Activity of Genes Is Highly Regulated by
References
41
the Protein Products of Other Genes
1 3
The Molecular Approach Is Applied t oEukaryotic Cells
13
CHAPTER 2 Molecules in Cells
4 3
References
14
Proteins
44
Amino Acids-the Building Blocks o f
• Proteins-Differ Only in Their Side Chains
44
Polypeptides Are Polymers Composed o f
I
Amino Acids Connected by Peptide Bonds
46
PART 1
Three-dimensional Protein Structure Is
Molecules, Cells, Proteins, and
Determined through X-ray Crystallography
46
Experimental Techniques: A Primer
17
The Structure of a Polypeptide Can BeDescribed at Four Levels
47
Two Regular Secondary Structures AreCHAPTER 1 Chemical Foundations
19
Particularly Important
48
Energy
20
Many Proteins Are Organized into Domains
S O
Chemical Bonds
20
Regions of Similar Architecture Often HaveSimilar Sequences
51The Most Stable Bonds between Atoms Are
Many Proteins Contain Tightly Boun dCovalent
20
Prosthetic Groups
52Noncovalent Bonds Stabilize the Structures of
Covalent Modifications Affect the Structure sBiological Molecules
23
and Functions of Proteins
53
Chemical Equilibrium
27
The Native Conformation of a Protein CanpH and the Concentration of Hydrogen Ions
28
Be Denatured by Heat or Chemicals
54
Water Dissociates into Hydronium and
Many Denatured Proteins Can Renature intoHydroxyl Ions
28
Their Native State
54
Enzymes
SS
Glycolipids of Various Structures Are Foun d
Certain Amino Acids in Enzymes Bind
in the Cell Surface Membrane
8 1
Substrates : Others Catalyze Reactions on the
The Primacy of Proteins
8 2Bound Substrates
56
Summary
8 2Trypsin and Chymotrypsin Are Well-
References
8 3characterized Proteolytic Enzymes
56
Coenzymes Are Essential for Certain
CHAPTER 3 Synthesis of Proteins andEnzymatically Catalyzed Reactions
59
Nucleic Acids
85Substrate Binding May Induce aConformational Change in the Enzyme
60
Rules for the Synthesis of Proteins andThe Catalytic Activity of an Enzyme Can Be
Nucleic Acids
86
Characterized by a Few Numbers
61
Protein Synthesis : The Three Roles of RNA
87
The Actions of Most Enzymes Are Regulated
62
Messenger RNA Carries Information from
Antibodies
65
DNA in a Three-Letter Genetic Code
88
Antibodies Can Distinguish among Closely
Synthetic mRNA and Trinucleotides Break th e
Similar Molecules
65
Code
89
Antibodies Are Valuable Tools for Identifying
The Anticodon of Transfer RNA Decode s
and Purifying Proteins
66
mRNA by Base Pairing with Its Codon
9 1
Aminoacyl-tRNA Synthetases Activate tRNA
93Nucleic Acids
66Each tRNA Molecule Must Be Identifiable b y
Nucleic Acids Are Linear Polymers of
a Specific tRNA Synthetase
94Nucleotides Connected by Phosphodieste rBonds
66
Ribosomes Are Protein-synthesizing Machines
95
DNA
68
The Steps in Protein Synthesis
99
The Native State of DNA Is a Double Helix
AUG Is the Initiation Signal in mRNA
99
of Two Antiparallel Chains with
Initiation Factors, tRNA, mRNA, and th eComplementary Nucleotide Sequences
69
Small Ribosomal Subunit Form an Initiatio n
DNA Is Denatured When the Two Strands
Complex
100
Are Made to Separate
71
Ribosomes Use Two tRNA-binding Sites (A
Many DNA Molecules Are Circular
72
and P) during Protein Elongation
100
Many Closed Circular DNA Molecules Are
UAA, UGA, and UAG Are the Terminatio n
Supercoiled
72
Codons
10 1
RNA Is Usually Single stranded and Serves
Rare tRNAs Suppress Nonsense Mutations
101
Many Different Functions
73
Nucleic Acid Synthesis
101
Lipids and Biomembranes
75
Nucleic Acid Synthesis Can Be Described byFive Rules
10 1Fatty Acids Are the Principal Components o fMembranes and Lipids
75
Chemical Differences between RNA andDNA Provide Functional Properties
106Phospholipids Are Key Components ofBiomembranes
76
Summary
107
Certain Steroids Are Components of
References
107
Biomembranes
76
Phospholipids Spontaneously Form Micelles
CHAPTER 4 The Study of Cellor Bilayers in Aqueous Solutions
77
Organization and SubcellularStructure
109Carbohydrates
77
Many Important Sugars Are Hexoses
77
Prokaryotic and Eukaryotic Cells
11 1
Polymers of Glucose Serve as Storage
Prokaryotes Have a Simpler Structure Tha nReservoirs
79
Eukaryotes
11 1
Glycoproteins Are Composed of Proteins
Eukaryotic Cells Have Complex Systems ofCovalently Bound to Sugars
80
Internal Membranes and Fibers
113
Prokaryotes and Eukaryotes Contain Similar
Proteins Are Secreted by the Fusion of a nMacromolecules
114
Intracellular Vesicle with the Plasm a
Prokaryotes and Eukaryotes Differ in the
Membrane
139
Amount of DNA per Cell
116
Small Vesicles May Shuttle Membran e
The Organization of DNA Differs in
Constituents from One Organelle to Another
140
Prokaryotic and Eukaryotic Cells
116
Lysosomes Contain a Battery of DegradativeEnzymes That Function at pH 5
140Light Microscopy and Cell Architecture
117
Vacuoles in Plant Cells Store Small Molecule sStandard Light (Bright-field) Microscopy
and Enable the Cell to Elongate Rapidly
142Utilizes Fixed, Stained Specimens
118
Contractile Vacuoles in Certain Protozoan sImmunofluorescence Microscopy Reveals
Function in Osmotic Regulation
143Specific Proteins and Organelles within a Cell
120Peroxisomes Produce and Degrade Hydrogen
The Confocal Scanning Microscope Produces
Peroxide
144Vastly Improved Fluorescent Images
122
The Mitochondrion Is the Principal Site ofDark-field Microscopy Allows Detection of
ATP Production in Aerobic Cells
144Small Refractile Objects
123 Chloroplasts Are the Sites of Photosynthesis
145Phase-contrast and Nomarski InterferenceMicroscopy Visualize Living Cells
125
The Plasma Membrane Has Many Varied an dEssential Roles
145
Electron Microscopy
126
Cilia and Flagella Are Motile Extensions o f
Transmission Electron Microscopy Depends
the Eukaryotic Plasma Membrane
145
on the Differential Scattering of a Beam of
Microvilli Enhance the Absorption o fElectrons
126
Nutrients
146
Minute Details Can Be Visualized on Viruses
The Plasma Membrane Binds to the Cell Wal land Subcellular Particles
127
or the Extracellular Matrix
146
Scanning Electron Microscopy Visualizes
Summary
148Detail on the Surface of Cells or Particles
128
References
148
Sorting Cells and Their Parts
12 9
Flow Cytometry Is Used to Sort Cells
129CHAPTER 5 Growing and Manipulating
Fractionation Methods Isolate Subcellular
Cells and Viruses
15 1Structures
130
Velocity Centrifugation Separates on the Basis
Types of Cell Division
152of Size and Density
132
The Cell Cycle in Prokaryotes Consists ofEquilibrium Density-gradient Centrifugation
DNA Replication Followed Immediately b ySeparates Materials by Density Alone
133
Cell Division
152Immunological Techniques Can Yield Pure
Eukaryotic DNA Synthesis Occurs in aPreparations of Certain Organelles
133
Special Phase of the Cell Cycle
152
The Organelles of the Eukaryotic Cells
134
Mitosis Is the Complex Process Tha tThe Eukaryotic Nucleus Is Bound by a
Apportions the New Chromosomes Equall yDouble Membrane
134
to Daughter Cells
154
The Nucleus Contains the Nucleolus, A
Meiosis Is the Form of Cell Division i nFibrous Matrix, And DNA-Protein Complexes
134
Which Haploid Cells Are Produced from
The Cytosol Contains Many Cytoskeletal
Diploid Cells
156
Elements and Particles
136
The Growth of Microorganisms and Cells i n
The Endoplasmic Reticulum Is an
Culture
159
Interconnected Network of Internal
Escherichia coli Is a Favorite Organism o fMembranes
138
Molecular Biologists
159
Golgi Vesicles Process Secretory Proteins and
Genes Can Be Transferred between Bacteri aPartition Cellular Proteins and Membranes
139
in Three Ways
161
The Yeast Life Cycle Includes Haploid and
Labeled Precursors Can Trace the Assembl yDiploid Phases
164
of Macromolecules and Their Distribution i n
Cultured Animal Cells Share Certain Growth
a Cell
193
Requirements and Capacities
166Determining the Size of Nucleic Acids and
Cell Fusion: An Important Technique in
Proteins
194
Somatic-Cell Genetics
170
Centrifugation Is Used to Separate Particle s
Hybrid Cells Containing Chromosomes from
and Molecules that Differ in Mass or Density
195
Different Mammals Assist in Gene-mapping
Electrophoresis Separates Molecule sStudies
170
According to Their Charge-Mass Ratio
198Mutants in Salvage Pathways of Purine andPyrimidine Synthesis Are Good Selective
Gel Electrophoresis Can Separate Mos tMarkers
171
Proteins in a Cell
200
Hybridomas Are Fused Lymphoid Cells That
In Vitro Protein Synthesis and Ge lMake Monoclonal Antibodies
172
Electrophoresis Provide an Assay forMessenger RNA
20 1DNA Transfer into Eukaryotic Cells
173
Yeast Cells Exhibit Homologous
Examining the Sequences of Nucleic AcidsRecombination of Foreign DNA in Contrast
and Proteins
202to Nonspecific Integration in Mammalian
173
Molecular Hybridization of Two Nucleic Aci dCells
Strands Can Be Detected in Several Ways
202Foreign DNA Can Be Introduced into theGerm Line of Animals to Produce Transgenic
Fingerprinting (Partial Sequence Analysis )
Strains
174
Allows Quick Comparisons ofMacromolecules
206Plants Can Be Regenerated from Plant Cel lCultures
175
Restriction Enzymes Allow the Precis eMapping of Specific Sites in DNA
206
Viruses: Structures and Function
176
The Sequence of Nucleotides in LongMost Viral Host Ranges Are Narrow
178
Stretches of DNA Can Be Rapidl y
Viruses Can Be Accurately Counted
179
Determined
212
Viral Growth Cycles Can Be Divided into
Proteins Can Be Sequenced Automatically
213Stages
179
Bacterial Viruses Are Widely Used to
Recombinant DNA : Selection and ProductionInvestigate Biochemical and Genetic Events
180
of Specific DNA
21 4
Plant Viruses Proved That RNA Can Act as a
cDNA Clones Are Whole or Partial Copies o f
Genetic Material
181
mRNA
215
Animal Viruses Are Very Diverse
181
Genomic Clones Are Copies of DNA fro m
Summary
186
Chromosomes
21 7
References
186
Vectors for Recombining DNA Exist in Man yCell Types
21 8
The Polymerase Chain Reaction Amplifie sCHAPTER 6 Manipulating Macromolecules
189
Specific DNA Sequences in a Mixture
21 9
Radioisotopes : The Indispensible Modern
Controlled Deletions and Base-specifi cMeans of Following Biological Activity
190
Mutagenesis of DNA
21 9
Radioisotopes Are Detected by Autoradiology
Synthetic Peptide and Nucleotide Sequences :or by Quantitative Assays
191
Their Use in Isolating and Identifying Genes
220Pulse-chase Experiments Must Be Designed
Summary
222with Knowledge of the Cell's Pool of Amin oAcids and Nucleotides
192
References
223
Control of Transcriptional Termination
249
Rho-independent Chain Termination I sAssociated with Certain Structural Features i n
PART II
the Termination Site
249
Gene Expression, Structure, and
Rho-dependent Chain Termination Requires
Replication
227
the Presence of a Specific Protein
250
Attenuation Provides Secondary Control o f
CHAPTER 7 RNA Synthesis and Gene
Chain Termination
250
Control in Prokaryotes
229
Antitermination Proteins Prevent Terminationand Allow "Read-Through" Control
252
Overall Strategy of Prokaryotic Gene Control
230
Bacteriophage A Infection : Alternative
Control of Transcriptional Initiation
231
Physiologic States Determined by a Comple xTranscriptional Control Program
253Initiation of Transcription in Prokaryote sEntails Sequence Recognition by RNA
A Repressor (cl Protein) Predominates i n
Polymerase Plus Sigma Factors
231
Lysogenic State
255
Operons Are Clusters of Genes Controlled at A Cro Protein Predominates during Lytic
One Promoter Site
234
Cycle
256
Bacterial Transcription Can Be Induced or
"Global Control" in E. coli
256
Repressed by Specific Nutrients
234
Stability of Biopolymers in Bacterial Cells
257
Regulatory Proteins Control the Access of
mRNAs Are Degraded Rapidly
257RNA Polymerase to Promoters in Bacterial
Synthesis of Some Ribosomal Proteins IsDNA
236
Regulated by Control of mRNA Translation
257Some Repressors Can Recognize Several
Bacterial Proteins Are Diluted or DestroyedOperators : The Arginine Regulon
238
When Not Needed
258Negative Control of Transcription: The
Summary
258Lactose Operon
240
Early Experiments with Regulatory Mutants
References
259
Suggested That Lactose Repressor Is a DNA-binding Protein
240CHAPTER 8 RNA Synthesis an d
Transcription of lac Operon Is Regulated by
Processing in Eukaryotes
26 1Repressor : The Jacob-Monod Model
242
Positive Control of Transcription : The
Relationship of Nuclear and CytoplasmicArabinose Operon
242
RNA
262
AraC Protein Binds at Several DNA Sites
Cell Fractionation and Labeling Experiment sIncluding Sites Distant from the Initiation Site
243
Reveal Locations and Classes of RNA
263
Regulation of ara Operon Involves Formation
Function and Structure of RNA Polymerases
266of DNA Loops
244
Three Polymerases Catalyze Formation o fCompound Control of Transcription
245
Different RNAs
266
A Single Protein, CAP, Exerts Positive
RNA Polymerases Have Complex Subuni tControl on Several Different Operons
245
Structure
266
The Galactose Operon Has Both a Regulated
Transcription Factors Assist Polymerases toand a Constitutive Promoter
245
Recognize Initiation Sites
267
Control of Regulatory Proteins
247
Three Methods for Mapping Transcription
Lacl and Some Other Repressors Are
Units
267
Synthesized Continually
247
Nascent-chain Analysis Provides "Snapshots "
Synthesis of Some Regulatory Proteins Is
of RNA Molecules during Synthesis
268
Under Autogenous Regulation
277
Electron Microscopy Can Visualiz e
Some Regulatory Proteins Are Controlled by
Transcription Units in Action
269
Conversion between Active and Inactive
Effect of UV Radiation on RNA Synthesi sForms
247
Can Be Used to Map Transcription Units
269
Synthesis and Processing of Pre-rRNA
270
Formation of 3' Poly A Involves Recognitio n
RNA Polymerase I Requires Species-specific
of Special Sequences, RNA Cleavage, and En d
Binding Factors to Begin Transcription
271
Addition
297
rDNA Termination Site Lies Downstream and
Methylation of Adenylate Residues I s
Initiation Site Lies Upstream from First Stable
Common in Vertebrate mRNAs
298
Transcript
272
Splice Sites in hnRNA Contain Shor t
Pre-rRNA Associates with Proteins and Is
Conserved Recognition Sequences near Intron
Cleaved within the Nucleolus to Form
Exon Boundaries
298
Ribosomal Subunits
273
Splicing of hnRNA Involves Concerted
Ribosomal RNA Genes Act as Nucleolar
Reactions to Excise Introns and Ligate Exons
299
Organizers
275
Small Ribonucleoprotein Particles Participat ein Splicing
300Synthesis and Processing of SS rRNA and
hnRNA Associates with Specific Proteins t otRNAs
275
Form Particles That May Assist in thePrimary 5S rRNA Transcript Undergoes Little
Assembly of Spliceosomes
302or No Processing
276Variations on the Splicing Theme, Including
The First Eukaryotic Transcription Factor to
Self-splicing
305Be Purified Is Required for Synthesis of 5 SrRNA
276
Splicing of Pre-tRNA Differs from Splicing ofPre-mRNA
305Processing of Pre-tRNA in the NucleusInvolves Splicing and Modification of Bases
278
Self-splicing of RNA Precursors Occurs i nSome Organisms
306RNA Polymerase III Requires Ordere dAddition of Multiple Factors to Begin
Portions of Two Different RNA TranscriptsTranscription
279
Can Be Joined by Trans-splicing
307
Nuclear Structure and the Passage of NuclearSynthesis and Processing of mRNAs : General
RNA to the Cytoplasm
307Pathway
280The Nuclear Matrix Is an Evolving Concept ,
mRNAs and hnRNAs Have Similar Base
Not Yet an Understood Structure
307Compositions but Differ in Length
280
Nuclear Pores Provide Passageways fo rMost Eukaryotic mRNAs Are Monocistronic
282
Movement of RNA into the Cytoplasm
308
Both Ends of mRNAs and hnRNAs Contain
Transport of mRNA May Be Assisted b yPosttranscription Modifications
283
Proteins
31 0
Splicing Is the Final Step in mRNA Processing
285
mRNAs May Be Directed toward SpecificSimilar Steps Occur in Formation of Most
Cytoplasmic Sites
31 0mRNAs
290Summary
31 1
Transcription of mRNA Genes by RNA
References
31 3Polymerase II
29 1
RNA Polymerase II Begins Transcription at 5 'Cap Sites
291
CHAPTER 9 The Structure of Eukaryotic
A Conserved DNA Sequence, the TATA Box,
Chromosomes
31 7
Is Responsible for Many Transcriptiona lInitiations
292
Morphology and Functional Elements ofEukaryotic Chromosomes
31 8RNA Polymerase II Requires Multiple Protei nFactors to Begin Transcription
293
Chromosome Number and Shape Are Species -specific
31 8Transcription by RNA Polymerase II I sEnhanced by Specialized Gene Activation
Cellular DNA Content Does Not Correlate
Sites
294
with Phylogeny
31 9
Transcription of mRNA Genes Is Terminated
Stained Chromosomes Have Characteristi c
Downstream of Poly A Site
296
Banding Patterns
321
Heterochromatin Consists of Chromosom eConversion of hnRNA to mRNA
297
Regions That Do Not Uncoil
322
Each Chromosome Contains One Linear
Pseudogenes Are Duplications That Hav eDNA Molecule
323
Become Nonfunctional
355
Human Chromosomes Can Be Mapped Based
Gene Duplication May Result from Unequa lon Restriction Fragment Length
Crossing Over
355Polymorphisms (RFLPs)
325 Gene Duplication Permits Expansion an dAutonomously Replicating Sequences,
Specialization of Gene Function
355Centomeres, and Telomeres Are Required for
Tandemly Repeated Genes Encoding rRNA,Replication and Stable Inheritance of
tRNA, and Histones
359Chromosomes
326
Structure o f Chromatin
330
Repeated Genes Are Necessary to MeetCellular Demand for Some Transcripts
356Amino Acid Sequences of Major Histones Are
Spacer Length between Tandem Genes Varies
358Highly Conserved
330
Histones and DNA Associate to Form
High-frequency Unequal Crossing Over an dGene Conversion May Help Maintain
Nucleosomes
331
Sequence Constancy in Gene Copies
359Chromatin Probably Unfolds durin gTranscription
334
Repetitious DNA Fractions
36 1
Nonhistone Proteins Provide a Structural
Simple-Sequence DNA
363
Scaffold for Long DNA Loops
336
Organisms Contain Several Types of Simple -
Chromatin Contains Small Amounts of DNA
Sequence Satellite DNA
363
binding Proteins in addition to Histones and
Most Simple-Sequence DNA Is Located i nTopoisomerases
338
Centromeres and Telomeres
363
Biologic Definitions of a Gene
338
Simple-Sequence DNA Units Are Conserve d
Recombination Tests Can Separate Linked
in Sequence but Not in Repeat Frequency
365
Genes
339
Intermediate Repeat DNA and Mobile DNA
Complementation Tests Can Distinguish
Elements
366
Genes Contributing to One Phenotypic
Movement of Bacterial Mobile Elements I sFunction
339
Mediated by DNA
367
Analyses of Phase di Mutants Led to
Many Eukaryotic Mobile Elements Ar eRecognition of Cistrons
341
Interspersed Genomic Copies of Cellula r
Molecular Definition of A Gene
342
RNAs
369
Transcription Units Are Not Necessarily
Movement Of Alu Sequences and Similar
Single Genes
342
Mobile Elements Is Mediated by RNA
372
Some Genes Do Not Encode Proteins
344
No Definite Function for Alu Sequences HasBeen Demonstrated
373A Gene Comprises All Nucleic AcidSequences Necessary to Produce a Functional
Most Mobile Elements in Yeast an d
Protein or RNA
344
Drosophila Are Long Intermediate Repeats
374
Summary
345
Yeast Ty And Drosophila copia Elements AreStructurally Similar to Retroviral DNA an d
References
345
Move by an RNA-mediated Mechanism
376
Movement Of Some Eukaryotic Mobil eElements Is Mediated by DNA
377CHAPTER 10 Eukaryotic Chromosomes and
Genes: Molecular Anatomy
347
Insertion of Mobile Elements Generall yProduces Genetic Effects
379
Major Classes of Eukaryotic DNA
348
Mobile Genetic Elements Must Move i nGametes to Affect the Evolution o f
Solitary Protein-coding Genes
349
Multicellular Organisms
380
Genes Compose Minor Portions of DNA
349
Functional Rearrangements in ChromosomalDuplicated Protein-coding Genes
350
DNA
38 1
Sequence Homology in Protein Families
Yeast Mating Types Can Switch by Gen eReflects Gene Duplication
350
Conversion
381
Trypanosome Surface Antigens Undergo
DNA-binding Proteins Can IncreaseFrequent Changes
384
Transcription in Vitro and in Vivo
407
Generalized DNA Amplification Produces
Acidic Domains of GAL4 Are Necessary fo rPolytene Chromosomes
385
Transcriptional Activation
41 1
Localized DNA Amplification of rRNA and
Transcriptional Control of Yeast CellOther Genes Occurs in Some Eukaryotic Cells
385
Specificity
41 2
Deletions Produce Immunoglobulin
Expression of GAL Genes in Yeast I sTranscription Units in Vertebrates
387
Controlled by Both Positive- and Negative-
Summary
388
acting Proteins
41 2
References
388
Yeast Mating Type Is Determined by anIntegrated Network of Transcriptiona lControls: A Model for Cell FateDetermination
41 2CHAPTER 11 Gene Control and the
Molecular Genetics of
Gene Control in Animal Cells
41 6
Development in Eukaryotes
391
A Cascade of Sequentially ExpressedTranscription Factors Directs Earl y
The "Purpose" of Gene Control in
Development in Drosophila
41 7Unicellular versus Multicellular Organisms
392
Many Different Signals Can Affect Eukaryoti cVariations in Proteins among Cell Types
392
Transcription Factors
422
The Three Components of Gene Control:
Terminal Differentiation Depends at Least inSignals, Levels, and Mechanisms
393
Part on Cell-specific Transcription Factors
426
Signals for Gene Control
394
Control of Regulatory-protein Activity and
Two General Types of Hormones Can Cause
Possible Effects of Chromatin Structure on
Differential Gene Expression
394
Gene Activity
429
Cell-Cell and Cell-Matrix Contacts Can Act
Control of Transcriptional Termination
43 1as Signals to Control Genes
395Differential Processing of Pre-mRNA
432Environmental and Nutritional Signals for
Cell-specific Processing of Pre-mRNA Ca nGene Control Are More Common inUnicellular than in Multicellular Organisms
395
Occur at Poly A and Splice Sites
433
Experimental Demonstration of
Differential Processing May Involve
Transcriptional Control
397
Variations in snRNPs
435
"Run-On" Transcriptional Analysis
Overlapping Transcription Units:
Accurately Measures Transcriptional Rates
397
Transcriptional Control Not ProcessingControl
43 6Differential Synthesis of Hepatocyte-specifi cmRNAs Depends on Cell-Cell Contact
399
Regulation of Ribosomal RNA
43 7
Differential Transcription of Globin Genes Is
Cytoplasmic Control of Gene Expression
43 7Related to Developmental Stage
399
Several Methods Are Used to Measure mRN AEnlarged "Puffs" on Insect Chromosomes
Half-Life
43 8Correspond to Regions with Increased
Degradation Rate of mRNA Is Related toTranscription
400
Poly A Tails and Specific Sequences in 3 'Structure and Function of DNA-binding
Untranslated Regions
438Proteins That Regulate Transcription of
Protein-coding Genes
400
Stability of Specific mRNAs Can B eRegulated by a Variety of Mechanisms
440Regulatory Sites in DNA and Cognate
Overall Rate of mRNA Translation Can BeBinding Factors Can Be Identified by
Controlled
442Molecular Genetic Techniques
401
Most, if Not All, Eukaryotic Protein-coding
Differential Translational Control of Specific
Genes Require Activators
401
mRNAs Is Not Common in Eukaryotes
444
Eukaryotic DNA-binding Proteins Exhibit a
Summary
444
Limited Number of Structural Designs
403
References
445
CHAPTER 12 DNA Replication, Repair,
E. coli RecA and RecBCD Proteins Promote
and Recombination
449
Recombination
48 1
Recombination in Yeast Probably InvolvesGeneral Features of DNA Synthesis and
Double-Strand Breaks
483Replication
450
Little Is Yet Known about Details of Meioti cDNA Replication Is Semiconservative
450
Recombination
484
DNA Synthesis Occurs Only during S Phase
Summary
484of Cell Cycle in Eukaryotes
451
References
485Most DNA Replication Is Bidirectional
454
Initiation and Propagation of a DNA Chainat a Growing Fork
456
• •
A Growing Fork Has a Continuous Leadin gStrand and a Discontinuous Lagging Stran dPrimed by RNA
456
PART IIIBidirectional Replication Bubbles Form after
Cell Structure and Function
489Initiation of DNA Synthesis on One TemplateStrand
457
Functional in Vitro Growing Forks Can Be
CHAPTER 13 The Plasma Membrane
49 1
Made with Purified Proteins and DNA
458
DNA Replication Begins at Specific
The Architecture of Lipid Membranes
492
Chromosomal Regions
462
All Membranes Contain Proteins and Lipids ;
Origin-binding Proteins Can Initiate DNA
Many Contain Carbohydrates
492
Replication in Vitro
464
The Phospholipid Bilayer Is the Basic
Replication of Linear Viral DNAs Begins at
Structural Unit of Biological Membranes
494
Ends of the Template and Uses Protein
Several Types of Evidence Point to th ePrimers
466
Universality of the Phospholipid Bilayer
496
Topoisomerases and Superhelicity in DNA
466
Phospholipid Bilayers and Biologica l
Linking Number, Twist, and Writhe Describe
Membranes Form Closed Compartments
497
DNA Superstructure
467
Phospholipid Bilayers Form a Two-
Topoisomerases Can Change the Linking
dimensional Fluid
498
Number
469
The Fluidity of a Bilayer Depends on Its
Topoisomerase II Is Involved in Releasing
Lipid Composition, Cholesterol Content, and
Final Products after Chromosome Replication
471
Temperature
498
Assembly of DNA into Nucleosomes
472
Membrane Proteins
499Newly Synthesized DNA Quickly Associates
Proteins Interact with Membranes in Differentwith Histones to Form Nucleosomes
472
Ways
500Repair of DNA
473
Some Integral Proteins Are Bound to theProofreading by DNA Polymerase Corrects
Membrane by Covalently Attached Lipids
500Copying Errors
473
Most Integral Membrane Proteins ContainEnvironmental DNA Damage Can Be
Long Segments of Hydrophobic Amino Acid sRepaired by Several Mechanisms
474
Embedded in the Phospholipid Bilayer
50 1
Recombination between Homologous DNA
Glycophorin Is Typical of Proteins That Spa nSites
477
the Membrane Once
50 1
Gene Conversion Can Occur near the
The Bacterial Photosynthetic Reaction Cente rCrossover Point During Reciprocal
Contains 4 Polypeptides and 1 1Recombination
478
Transmembrane a-Helices
502
Holliday Recombination Model and Its
The Orientation of Proteins in MembranesVariations Account for Gene Conversion
478
Can Be Experimentally Determined
504
In Vitro Integration of Phage A Mimics
Detergents Are Used to Solubilize and StudyRecombination Event
480
Integral Membrane Proteins
S04
Principles of Membrane Organization
506
CHAPTER 14 Transport across Cell
All Membrane Proteins Bind Assymetrically
Membranes
53 1to the Lipid Bilayer
506
The Two Membrane Leaflets Have Different
Passive Transport across the Cell Membrane
53 2
Lipid Compositions
506
Some Small Molecules Cross the Membran e
Freeze-fracture and Deep-etching Techniques
by Simple Diffusion
532
Reveal the Two Membrane Faces in Electron
Membrane Proteins Speed the Diffusion o fMicroscopy
507
Specific Molecules across the Membrane
534
Most Membrane Proteins and Lipids Are
Facilitated Diffusion Transports Glucose int oLaterally Mobile in the Membrane
507
Erythrocytes
535
Cytoskeletal Interactions Affect the
Ion Channels, Intracellular Ion Environment,Organization and Mobility of Surface
and Membrane Electric Potential
536Membrane Proteins
509
Simple Models Explain the Electric Potentia lThe Glycocalyx Is Made Up of Proteins and
across the Cell Membrane
537Oligosaccharides Bound to the Outer Surfac eof the Cell
510
Active Ion Transport and ATP Hydrolysis
539
The Erythrocyte Membrane: Cytoskeletal
Na + K + ATPase Maintains the Intracellula r
Attachment
510
Concentrations of Na and K Ions i nAnimal Cells
540The Erythrocyte Membrane Can Generate
z +Inside-out or Rightside-out Vesicles
S12
Ca ATPase Pumps Calcium Ions out of th eCytosol, Maintaining a Low Concentration
54 1The Erythrocyte Has Two Main IntegralMembrane Proteins
512
Coupling between ATP Hydrolysis and Io nPumping Requires an Ordered Kineti c
Erythrocyte Cytoskeletal Proteins Affect Cell
Mechanism
543Shape and Integral Protein Mobility
513Lysosomal and Vacuolar Membranes Contain
Erythrocyte Cytoskeleton Is Constructed of a
V-type ATP-dependent Proton Pumps
543Network of Fibrous Proteins Just beneath th eSurface Membrane
514
The Multidrug Resistance Gene May Encod ean ATP-driven Drug Transporter
544Several Hereditary Diseases Affect theCytoskeleton
516
Co transport: Symport and Antiport
545
Specialized Regions of the Plasma Membrane
516
Amino Acids and Glucose Transport into
The Pancreatic Acinus Is an Aggregate of
Many Animal Cells Is Directly Linked to Na+o
Entry (Symport)
545Cells Having Two Very Different Regions ofPlasma Membrane
517
Transport of Cat+ Out of Cells Is Ofte n
The Plasma Membrane of Intestinal Epithelial
Coupled to Na t+ Entry (Antiport)
54 7
Cells Is Divided into Two Regions of
Exchange of Cl' and HC0 3 - Anions acrossDifferent Structure and Function
518
the Erythrocyte Membrane Is Catalyzed byBand 3, an Anion-exchange Protein
54 7Microvilli Have a Rigid Structure
521Antiports Regulate Cytosolic pH
549Certain Epithelial Cells Can Be Grown inCulture
521
A Proton Pump and a Band 3-Like Anion -exchange
Cell
521
Protein Combine to Acidify th eTypes of
Junctions
Stomach Contents
549Tight Junctions Seal Off Body Cavities
521
Anion Channels and Proton Antiports EnableThe Tight Junction Separates the Apical and
Plant Vacuoles to Accumulate Ions an dBasolateral Domains of Polarized Epithelial
Metabolites
S5 1Cells
522
Transport Into Prokaryotic Cells
S5 1Gap Junctions Allow Small Molecules to Pass
Proton Symport Systems Import Man ybetween Adjacent Cells
523
Nutrients into Bacteria
55 1Plasmodesmata Interconnect the Cytoplasms
Certain Molecules Are Phosphorylated durin gof Adjacent Cells in Higher Plants
526
Passage across the Cell Membrane
552Summary
526
Osmosis, Movement of Water, and theReferences
527
Regulation of Cell Volume
553
Osmotic Pressure Causes Movement of Water
CHAPTER 1S Energy Conversion :across One or More Membranes
554
The Formation of ATP inMovement of Water Accompanies the
Mitochondria and Bacteria
583Transport of Ions or Other Solutes
554
Animal Cells Can Regulate Their Volume and
Energy Metabolism in the Cytosol
585
Internal Osmotic Strength
554
Glycolysis Is the First Stage in the
Changes in Intracellular Osmotic Pressure
Metabolism of Glucose and the Generation o f
Cause Leaf Stomata to Open
555
ATP
585
The Internalization o f Macromolecules and
In Glycolysis, ATP Is Generated by Substrat e
Particles
554
level Phosphorylation
586
Membrane Fusions Occur in Endocytosis,
Some Eukaryotic and Prokaryotic Cell s
Exocytosis, and Many Other Cellular
Metabolize Glucose Anaerobically
588
Phenomena
558
Carbohydrate Oxidation Is Completed in th e
Pinocytosis Is the Nonspecific Uptake of
Mitochondria, Where Most ATP Is Produced
588
Extracellular Fluids
558
Mitochondria and the Metabolism of
Phagocytosis Depends on Specific Interactions
Carbohydrates and Lipids
589
at the Cell Surface
559
The Outer and Inner Membranes of th e
Receptor-mediated Endocytosis
560
Mitochondrion Are Structurally an dFunctionally Distinct
589The Asialoglycoprotein Receptor Remove sCertain Abnormal Serum Glycoproteins
562
Acetyl CoA Is a Key Intermediate in th eMitochondrial Metabolism of Pyruvate
592The Low-density Lipoprotein (LDL) Recepto rMediates the Uptake of Cholesterol
The Metabolism of Fatty Acids Occurs in the
containing Particles
563
Mitochondrion and Also Involves Acetyl CoA
592
Ligand Binding and the Internalization of
The Citric Acid Cycle Oxidizes the Acety l
Receptor-Ligand Complexes Can Be Studied
Group of Acetyl CoA to CO 2 and Reduces
Separately
565
NAD and FAD to NADH and FADH 2
593
Clathrin, a Fibrous Protein, Forms a Lattice
Electrons Are Transferred from NADH and
Shell around Coated Pits and Vesicles
567
FADH2 to Molecular 02 by Electron Carrie rProteins
594Most Surface Receptors and MembranePhospholipids Are Recycled
568
The Electrochemical Proton Gradient Is Use dto Generate ATP from ADP and P i
595Ligands Are Uncoupled from Receptors b yAcidification of Endocytic Vesicles
569
The Proton-motive Force, ATP Generation,and Transport of Metabolite Closed Vesicles
A Hereditary Disease Is Due to a Genetic
Are Required for the Generation of ATP
596Defect in the LDL Receptor
569The Proton-motive Force Is Composed of a
Synthesis of the LDL Receptor and
Proton Concentration Gradient and aCholesterol Are Tightly Regulated
570
Membrane Electric Potential
596
Proteins Internalized by Receptor-mediated
The FoF I Synthase Complex Couples ATPEndocytosis Undergo Various Fates
570
Synthesis to Proton Movement down theTransferrin Delivers Iron to Cells by Receptor-
Electrochemical Gradient
597
mediated Endocytosis
571
Reconstitution of Closed Membrane Vesicle s
Entry of Viruses and Toxins into Cells
571
Supports the Role of the Proton-motive Forcein ATP Synthesis
600Endocytosis Internalizes Bacterial Toxins
572Many Transporters in the Inne r
Infection by Many Membrane-enveloped
Mitochondrial Membrane Are Powered b yViruses Is Initiated by Endocytosis
573
the Proton-motive Force
60 1
Low pH Triggers Fusion of the Viral and Cell
573
Inner-membrane Proteins Allow the Uptake o fMembranes
Electrons from Cytosolic NADH
602
HIV (AIDS) and Other Enveloped Viruses
NADH, Electron Transport, and ProtonFuse Directly with the Plasma Membrane
575
Pumping
604
Summary
576
Electron Transport in Mitochondria Is
References
578
Coupled to Proton Pumping
604
Most Electron Carriers Are Oriented in the
PSI Is Used for Both Linear and Cycli cTransport Chain in Order of Their Reduction
Electron Flow
62 8Potentials
608
PSI and PSII Are Functionally Coupled
62 9The in Vivo Order of the Electron Carriers
CO 2 Metabolism during Photosynthesis
63 1Can Be Determined with Certainty
609
Three Electron Transport Complexes Are
CO2 Fixation Is Catalyzed by Ribulose 1, 5
Sites of Proton Pumping
609
bisphosphate Carboxylase
63 1
Photorespiration Liberates CO 2 andMetabolic Regulation
611
Consumes 0 2
633
The Ratio of ATP Production to 0 2
The C4 Pathway for CO 2 Fixation Is Used byConsumed Is a Measure of the Efficiency of
Several Tropical Plants
633Oxidative Phosphorylation
611
Summary
636In Respiratory Control, Oxidation of NADH
References
636or FADH2 and ATP Production AreObligatorily Coupled through the Proton -motive Force
612
An Endogenous Uncoupler in Brown fat
CHAPTER 17 Plasma-membrane, Secretory,
Mitochondria Converts H + Gradients to Heat
612
and Lysosome Proteins :Biosynthesis and Sorting
63 9The Steps of Glycolysis Are Controlled b yMultiple Allosteric Effectors
613
The Synthesis of Membrane Lipids
64 1
Summary
613
Phospholipids Are Synthesized in Associatio nReferences
614
with Membranes
64 1
Special Membrane Proteins AllowPhospholipids to Equilibrate in Both
CHAPTER 16 Photosynthesis
617
Membrane Leaflets
643
Phospholipids Move from the ER to OtherAn Overview of Photosynthesis in Plants
618
Cellular Membranes
643Chloroplasts Have Three Membranes
618
Sites of Organelle- and Membrane-ProteinThylakoid Membranes Have Light-absorbing
Synthesis
644
Photosystems
620
All Cytoplasmic Ribosomes Are Functionall y
The Light-absorbing Steps of Photosynthesis
621
Equivalent
644
Each Photon of Light Has a Defined Amount
Different Proteins Are Synthesized b yMembrane-attached and Membrane-
of Energy
621
unattached Ribosomes
644Chlorophyll Is the Primary Light-absorbing
Overall Pathway for the Synthesis ofPigment
621
Secretory and Membrane Proteins
646
Molecular Analysis of Bacterial
Newly Made Secretory Proteins Are Localize dPhotosynthesis
622
to the Lumen of the Rough ER
646
Photosynthetic Bacteria Utilize Only One
Many Organelles Participate in Protei nPhotosystem and Do Not Evolve 0 2
622
Secretion
647
The Exact Pathway of Electron Transport in
Secretory Proteins Move from the Rough E Rthe Photosynthetic Reaction Center of Purple
to Golgi Vesicles to Secretory Vesicles
648Bacteria Is Known
624
Plasma-membrane Glycoproteins Follow th ePhotosynthetic Bacteria Can Carry Out
Same Maturation Pathway as Continuousl yNoncyclic Electron Transport
624
Secreted Proteins
648
The Structure and Function of the Two Plant
The Transport o f Secretory and Membran e
Photosystems: PSI and PSII
624
Proteins into or across the ER Membrane
650
Both PSI and PSII Are Essential for
How Polypeptides Cross the ER Membrane I s
Photosynthesis in Chloroplasts
624
Controversial
650
PSII Splits H 2 O
627
A Signal Sequence on Nascent SecretoryProteins Targets Them to the ER and Is The n
Electrons Are Transported from PSII to PSI
628
Cleaved Off
652
Several Receptor Proteins Mediate the
Several Proteolytic Cleavages Occur durin gInteraction of Signal Sequences with the ER
the Late Maturation Stages in Secretory andMembrane
653
Membrane Proteins
672
Some Secretory Proteins Can Cross the ER
Different Vesicles Are Used for Regulated andMembrane After Synthesis Is Complete
655
Continuous Protein Secretion
673
Topogenic Sequences Allow Integral Proteins
Proteolytic Maturation of Insulin Occurs into Achieve Their Proper Orientation in the
Acidic, Clathrin-coated Secretory Vesicles
673ER Membrane
655
Exocytosis Can Be Triggered by Neuron o r
Posttranslational Modifications of Secretory
Hormone Stimulation
674
and Membrane Proteins in the Rough ER
657
Regulated Secretory Vesicles Swell Following
Disulfide Bonds Are Formed during or soon
Fusion with the Plasma Membrane
675
after Synthesis
658
Apical-basolateral Protein Sorting Occurs i nthe Golgi Complex or the Basolatera l
Formation of Oligomeric Proteins Occurs in
Membrane
675the ER
659
Only Properly Folded Proteins Are
Membranes Recycle in Secretory Cells
676
Transported from the Rough ER to the Golgi
Summary
676Complex
659
References
678ER-specific Proteins Are Selectively Retainedin the Rough ER
660
Golgi Vesicles: Sorting and Glycosylation of
CHAPTER 18 Organelle Biogenesis : TheSecretory and Membrane Proteins
661
Nucleus, Chloroplast, an dN-Linked and 0-Linked Oligosaccharides
Mitochondrion
68 1
Have Very Different Structures
661
Assembly and Disassembly of the Nuclear0-Linked Sugars Are Synthesized in the ER
Membrane
682or Golgi Vesicles from Nucleotide Sugars
663Lamina Proteins Are a Principal Determinan t
The Golgi Membrane Contains Permeases for
of Nuclear Architecture
682Nucleotide Sugars
663Lamin Phosphorylation Is Correlated wit h
The Diverse N-Linked Oligosaccharides Share
Disassembly of the Nuclear Membrane
683Certain Structural Features
664
Chromatin Decondensation and Lami nN-Linked Oligosaccharides Are Synthesized
Dephosphorylation Initiate Nuclea rfrom a Common Precursor and Subsequently
Reassembly
683Processed
665Protein Import into the Cell Nucleus
683Modifications to N-Linked Oligosaccharide sAre Completed in the Golgi Vesicles
666
Most Nuclear Proteins Are Selectivel yImported into Nuclei
684N-Linked and 0-Linked Oligosaccharides
Nuclear Pores Are the Portals for ProteinMay Stabilize Maturing Secretory andMembrane Proteins
667
Import
685
Different Proteins Utilize Different Signa lGolgi and Post-Golgi Sorting and Processing
Sequences for Nuclear Import
685of Secretory and Membrane Proteins
667
Mitochondrial DNA: Structure, Expression,Vesicles Transport Proteins from Organelle to
and Variability
686Organelle
667
Cytoplasmic Inheritance and DNA SequencingThe Steps in Vesicular Transport Can Be
Have Established the Existence o fStudied Biochemically and Genetically
669
Mitochondrial Genes
686
Phosphorylated Mannose Residues Target
The Size and Coding Capacity of mtDNAProteins to Lysosomes
669
Varies in Different Organisms
688
Genetic Defects Have Elucidated the Role of
Mitochondrial Genetic Codes Are Different i nMannose Phosphorylation
670
Different Organisms
690
Propeptide Sequences Target Proteins to
Animal Mitochondrial RNAs UndergoVacuoles
671
Extensive Processing
690
Yeast mtRNAs Are Transcribed from
The K D Values for Hormone ReceptorsMultiple Promoters and Spliced
691
Approximate the Concentration of theCirculating Hormone
720Synthesis and Localization of Mitochondriat
Affinity Techniques Permit Purification ofProteins
693
Receptor Proteins
720Most Mitochondrial Proteins Are Synthesize din the
Many Receptors Can Be Cloned withoutCytosol as Precursors
693
Prior Purification
720Multiple Signals Target Proteins to theCorrect Submitochondrial Compartment
Receptors and the Activation ofompartment
695
Adenylateri e Rene
72 2Translocation Intermediates Can BeAccumulated and Studied
696
Functional Assays Establish the Identity of th ePurified ß-Adrenergic Receptor
723Uptake of Mitochondrial Proteins Require sEnergy
Analogs Are Important in the Studygy
697
of Receptor Action
724Synthesis of Mitochondrial Proteins I sCoordinated
699
The Binding of Hormone to ß-AdrenergicReceptors Activates Adenylate Cyclase
726Chloroplast DNA and Biogenesis of Plastids
699
The G S Protein Cycles between Active an dChloroplast DNA Contains over 120
Resting Forms
72 6Different Genes
699
Several Receptors Interact with a Single TypeMany Proteins Are Synthesized in the Cytosol
of Adenylate Cyclase
728and Imported into Chloroplalsts
700
Several Bacterial Toxins Irreversibly Modif yProplastids Can Differentiate into
G Proteins
72 9Chloroplasts or Other Plastids
702
All Receptors That Interact with G Protein sPhytochromes Mediate Light Induction of
Share Common Structural Features
73 0Gene Expression in Plants
704
Degradation of cAMP Is Also Regulated
730Summary
705
cAMP and Regulation of CellularReferences
706
Metabolism
730
cAMP Activates a Protein Kinase
730
Glycogen Synthesis and Degradation AreCHAPTER 19 Cell-to-Cell Signaling:
Controlled by cAMP
732Hormones and Receptors
709
cAMP-dependent Protein Kinases Regulate th eEnzymes of Glycogen Metabolism
732The Role of Extracellular Signals in CellularMetabolism
710
One Function of the Kinase Cascade IsAmplification
735Specific Receptors Mediate the Response o fCells to Extracellular Signals
711
cAMP Operates in All Eukaryotic Cells
735
Most Lipophilic Hormones Interact with
Cat+ Ions, Inositol Phosphates, and 1,2 -Cytosolic or Nuclear Receptors to Affect
Diacylglycerol as Second Messengers
73 6
Gene Expression
712
Calmodulin Mediates Many Cellular EffectsWater-soluble Hormones Interact with Cell
of Ca" Ions
73 6surface Receptors
715
Ca t+ Ions Control Hydrolysis of Muscl eProstaglandins Are Produced by Most
Glycogen
73 6
Mammalian Cells
717
Local Concentrations of Cat+ Ions in theThe Synthesis, Release, and Degradation of
Cytosol Can Be Monitored by Fluorescence
73 8Hormones Are Regulated
717
Inositol 1,4,5-Trisphosphate Causes th eThe Levels of Hormones Are Regulated by
Release of Ca" Ions from the ER
738Complex Feedback Circuits
718
1,2-Diacylglycerol Activates Protein Kinase C
742
Identification and Purification of Cell-
Insulin and Glucagon: Hormone Regulationsurface Receptors
719
ofBlood Glucose Levels
743
Hormone Receptors Are Detected by a
Insulin Controls Cell Growth and Also theFunctional Assay
719
Level of Blood Glucose
743
The Insulin Receptor Is a Ligand-activated
Membrane Potentials Can Be Measured with
Protein Kinase
745
Microelectrodes
77 0
Insulin and Glucagon Balance Blood Glucose
The Action Potential Reflects the Sequentia lLevels
745
Depolarization and Repolarization of a
Abnormal Function of Insulin Receptors Is
Region of the Nerve Membrane
77 0
One Cause of Diabetes
745
Changes in Ion Permeabilities Cause Specific ,
Receptor Regulation
747
Predictable Changes in the Membran ePotential
771The Receptor Number Is Down regulated by
A Transient Increase in Sodium PermeabilityEndocytosis
747
Depolarizes the Nerve Membrane duringPhosphorylation of Cell-surface Receptors
Conductance of an Action Potential
773Modulates Their Activity
748
Opening and Closing of Voltage-dependentHormones and Cell-to-Cell Signaling in
Channel Proteins Change PNa and PK
774Microorganisms
749
The Action Potential Is Induced in an All-or-A Pheromone Attracts Yeast Cells for Mating
749
Nothing Fashion
774
Aggregation in Cellular Slime Molds Is
The Movement of Only a Few Sodium IonsDependent on Cell-to-Cell Signaling
751
Generates the Action Potential
77 6
Plant Hormones and Plant Growth and
Membrane Depolarizations Spread Only Shor tDifferentiation
752
Distances without Voltage-gated Sodiu m
Auxin Triggers the Elongation of Higher
Channels
776
Plant Cells
753
Myelination Increases the Rate of Impuls e
Auxin Causes Rapid Changes in Gene
Conduction
778
Expression
754Molecular Properties of Voltage-gated Io n
Auxin Transport Requires Specific Transport
Channel Proteins
78 0Proteins in Polarized Mesothelial Cells
755Patch Clamps Permit Measurement of Io n
Cytokinins Stimulate Cell Division
756
Movements through Single Sodium Channels
78 0
Gibberellic Acid Triggers Seed Germination
The Sodium Channel Protein Has Fourby Inducing Specific mRNAs
756
Homologous Transmembrane Domains Each
Ethylene Promotes Fruit Ripening and
Containing a Voltage Sensor
78 1
Abscission
757
Shaker Mutants in Drosophila melanogasterAbscissic Acid Has General Growth-
Led to the Identification of a Voltage-gate d
inhibitory, Senescence-promoting Activity
758
Potassium Channel Protein
784
Summary
758
All Voltage-gated Ion Channel ProteinsProbably Evolved from a Common Ancestra l
References
759
Channel-protein Gene
784
Synapses and Impulse Transmission
78 4
CHAPTER 20 Nerve Cells and the Electric
Nearly Instantaneous Impulse Transmission
Properties of Cell Membranes
763
Occurs across Electric Synapses
78 5
Chemical Synapses Can Be Excitatory o rNeurons, Synapses, and Nerve Circuits
764
Inhibitory and Can Exhibit Signa l
The Neuron Is the Fundamental Unit of All
Amplification and Computation
785
Nervous Systems
764
Many Chemicals Function a s
Synapses Are Specialized Sites 'Where Neurons
Neurotransmitters
786
Communicate with Other Cells
765
Neurotransmitter Receptors Are Coupled to
The Decision to Fire an Action Potential
Ion Channels in Different Ways
786
Involves Summation of Electric Disturbances
767
Synaptic Transmission and the NicotinicNeurons Are Organized into Circuits
767
Acetylcholine Receptor
78 9
The Action Potential and Conduction of
Acetylcholine Is Synthesized in the CytosolElectric Impulses
768
and Stored in Synaptic Vesicles
789
Exocytosis of Synaptic Vesicles Is Triggered
CHAPTER 21 Microtubules and Cellula rby Opening of Voltage-gated Calcium
Movements
81 5Channels and a Rise in Cytosolic Calcium
790
Synaptic Vesicle Exocytosis and Endocytosis
Structure and Diversity of Microtubules
81 6Are Ordered Processes
790
All Microtubules Have a Defined Polarity an dThe Nicotinic Acetylcholine Receptor Protein
Are Composed of a- and ß-Tubulin
81 7Is a Ligand-gated Cation Channel
791
Microtubules Form a Diverse Array of Bot hSpontaneous Exocytosis of Synaptic Vesicles
Permanent and Transient Structures
81 7Produces Small Depolarizations in thePostsynaptic Membrane
792
Structural and Kinetic Polarity of
Nicotinic Acetylcholine Receptor ContainsMicrotubules
81 8
Five Subunits, Each of Which Contributes to
Microtubule Assembly and Disassembl ythe Cation Channel
792
Occur by Preferential Addition and Loss o f
Prolonged Exposure to Acetylcholine Agonists
aß Dimers at the (+) End
81 9
Desensitizes Cholinergic Receptors
794
Colchicine and Other Treatments Can Shif tMicrotubule Assembly-Disassembly Stead yHydrolysis of Acetylcholine Terminates the
State
820Depolarization Signal
794Microtubules Contain Microtubule-associate d
Functions of Other Neurotransmitters and
Proteins
822Their Receptors
796The Microtubule-organizing Cente r
Cardiac Muscarinic Acetylcholine Receptor
Determines the Polarity of CellularActivates a G Protein and Opens Potassium
Microtubules
823Channels
797Microtubules Grow from MTOCs
823Catecholamines Are Widesprea dNeurotransmitters
797
Microtubules in Cells Elongate and Shrin kfrom Their Distal (+) Ends
823Some Receptors for Neurotransmitters Affec tAdenylate Cyclase
798
In the Same Cells Some Microtubules Ar eGrowing While Others Are Shrinking
82 6GABA and Glycine Are the Neurotransmitter sat Many Inhibitory Synapses
798
Heterogenity of a- and ß-Tubulin
828
Some Peptides Function as Both
Vertebrates Have Genes Encoding CloselyNeurotransmitters and Neurohormones
799
Related a- and ß-Tubulins
829
Endorphins and Enkephalins Are
a-Tubulin Undergoes Reversible Covalen tNeurohormones That Inhibit Transmission of
Modifications
830Pain Impulses
799Intracellular Transport via Microtubules
830Memory and Neurotransmitters
800
Fast Axonal Transport Occurs alongMutations in Drosophila Affect Learning and
Microtubules
83 0Memory
800
Microtubules Provide Tracks for MovementGill-withdrawal Reflex in Aplysia Exhibits
of Pigment Granules and Golgi Vesicles
832Three Elementary Forms of Learning
800
Specific Proteins Promote VesicleSensory Transduction: The Visual System
802
Translocation along Microtubles
832
Hyperpolarization of Rod Cells Is Caused by
Cilia and Flagella : Structure and Movement
836Closing of Sodium Channels
803
Absorption of a Photon Triggers
All Eukaryotic Cilia and Flagella Have
Isomerization of Retinal and Activation of
Similar Structures
836
Opsin
805
Dynein ATPases Are Essential to the
Cyclic GMP Is a Key Transducing Molecule
806Movement of Flagella and Cilia
838
Rod Cells Adapt to Varying Levels of
Sliding of Microtubules Is Coverted into
Ambient Light
807Bending of the Axoneme
840
Genetic Studies Provide Additiona lSummary
808
Information on Axoneme Assembly an dReferences
810
Beating
840
Basal Bodies and Centrioles: Structure and
Striated Muscle Consists of a Regular ArrayProperties
840
of Actin and Myosin Filaments
865
Centrioles and Basal Bodies Are Built of
Thick and Thin Filaments Move Relative t oMicrotubules
841
Each Other during Contraction
867
Centrioles and Basal Bodies Contain a Unique
ATP Hydrolysis Powers the Contraction ofSmall DNA
842
Muscle
868
Centrioles Can Convert into Basal Bodies and
Release of Calcium from the SarcoplasmicVice Versa
842
Reticulum Triggers Contraction
870
Function of Microtubules in Mitosis
844
Calcium Activation of Actin, Mediated by
Light-Microscope Techniques Reveal the
Tropomyosin and Troponin, Regulate s
Mitotic Spindle in Living Cells
844
Contraction in Striated Muscle
872
Bundles of Microtubules Form the Mitotic
Calcium Activation of Myosin Light Chain s
Spindle
847
Regulates Contraction in Smooth Muscle an dInvertebrate Muscle
873Kinetochore Microtubules Connect the
cAMP, 1,2-Diacylglycerol, and CaldesmonChromosomes to the Poles
848
Also Affect Contractability of Smooth Muscle
873Dynamic Instability Explains the
Smooth and Striated Muscles Contai nMorphogenesis of the Mitotic Spindle
849
Functionally Different Myosin Light ChainsMany Events in Mitosis Do Not Depend on
and Tropomyosins
875the Mitotic Spindle
850
Proteins Anchor Actin Filaments to theBalanced Forces Align Metaphase
Plasma Membrane or the Z Disk
875Chromosomes at the Equator of the Spindle
850Long Proteins Organize the Sarcomere
878Anaphase Consists of Two Distinct Motil eEvents
851
Dystrophin Is a Muscle Protein Identified byStudy of a Genetic Disease
878Poleward Chromosome Movement (Anaphase
Phosphorylated Compounds in Muscle Act a sA) Is Powered by Microtubule Disassembly at
a Reservoir for ATP Needed for Contraction
879the Kinetochore and Requires No Externa lEnergy Source
851
Actin and Myosin in Nonmuscle Cells
879Separation of the Poles (Anaphase B) Involves All Vertebrates Have Multiple Actin Gene sSliding of Adjacent Microtubules Powered by
and Actin Proteins
880ATP Hydrolysis
852
Cytokinesis Is the Final Separation of the
Many Actin-binding Proteins Are Present i n
Daughter Cells
853
Nonmuscle Cells
880
Noncontractile Bundles of Actin Filament sSummary
855
Maintain Microvilli Structure
88 1References
855
Actin and Myosin Are Essential fo rCytokinesis in Nonmuscle Cells
884
Movements of the Endoplasmic Reticulu mCHAPTER 22 Actin, Myosin, and
along Actin Filaments Power CytoplasmicIntermediate Filaments : Cell
Streaming
885Movements and Cell Shape
859
Polymerization of Actin Monomers I sControlled by Specific Actin-binding Proteins
Actin and Myosin Filaments
860
in Nonmuscle Cells
885
Actin Monomers Polymerize into Long
Movement of Amebas and Macrophage sHelical Filaments
860
Involves Reversible Gel-Sol Transitions of an
Actin Filaments Are Intrinsically More Stable
Actin Network
888
Than Microtubules
861
Movements of Fibroblasts and Nerve Growth
Myosin Is a Bipolar, Fibrous Molecule That
Cones Involve Controlled Polymerization an d
Binds Actin
862
Rearrangements of Actin Filaments
890
Driven by ATP Hydrolysis, Myosin Heads
Actin Stress Fibers Permit Cultured Cells t o
Move along Actin Filaments
863
Attach to Surfaces
892
Muscle Structure and Function
865
Intermediate Filaments
894
Different Intermediate Filament Proteins Are
Laminin, Fibronectin, and OtherExpressed in Different Cell Types
894
Multiadhesive Matrix Glycoproteins
920
All Intermediate Filaments and Their Subunit
Laminin Is a Principal Structural Protein o fProteins Have a Similar Structure
895
All Basal Lamina
920
Intermediate Filaments Are Often Associated
Fibronectins Bind Many Cells to Fibrou swith the Cell Nucleus and with Microtubules
896
Collagens and to Other Matrix Components
922
Intermediate Filaments Stabilize Epithelia by
Fibronectin Promotes Cell Adhesion to th eConnecting Spot Desmosomes
897
Substratum
923
Summary
898
Fibronectins Promote Cell Migration
924
References
899
Cell-Cell Adhesion Proteins
924
E-Cadherin Is a Key Adhesive Molecule for
CHAPTER 23 Multicellularity: Cell-Cell
Epithelial Cells
926
and Cell-Matrix Interactions
903
Cadherins Influence Morphogenesis an dDifferentiation
92 6The Extracellular Matrix Serves Many
N-CAMs Are a Set of Cat+ -Independen tFunctions
904
Adhesive Molecules Encoded by a SingleCollagen: A Class of Multifunctional Fibrous
Gene
92 8Proteins
906
The Basic Structural Unit of Collagen Is a
Cell and Matrix Interactions duringDevelopment
92 9Triple Helix
906Mesodermal Cells Determine the Type o f
Most Collagen Exons Encode Six Gly-X-Y
Structure Made by the Epidermis
92 9Sequences
907Neuroectodermal Cells Induce Epithelial Cells
Collagen Fibrils Form by Lateral Interactions
to Differentiate into a Lens
92 9of Triple Helices
907Cell Interactions Are Essential For Formatio n
Denatured Collagen Polypeptides Cannot
of Internal Organs
93 0Renature to Form a Triple Helix
909The Basal Lamina Is Essential fo r
N-Terminal and C-Terminal Propeptides Aid
Differentiation of Many Epithelial Cells
93 1in the Formation of the Triple Helix
909
Newly Made Collagen Is Modified
Cell and Matrix Interactions during Neuron
Sequentially in the Rough ER and the Golgi
Development
932
Complex
909
Individual Neurons Can Be Identified
Procollagen Is Assembled into Fibers after
Reproducibly and Studied
933
Secretion
910
Growth Cones Guide the Migration an d
Mutations in Collagen Reveal Aspects of Its
Elongation of Developing Axons
933
Structure and Biosynthesis
912
Adjacent Motor Neurons Follow Differen t
Collagens Form a Diversity of Fibrillar
Pathways to Different Target Muscles
934
Structures
913
Different Growth Cones Navigate along
Type IV Collagen Forms the Two-dimensional
Different Axons
935
Reticulum of the Basal Lamina
914
The Basal Lamina at the Neuromuscular
Hyaluronic Acid and Proteoglycans
915
Junction Directs Differentiation o fRegenerating Nerve and Muscle
93 7HA Is an Immensely Long, Negativel yCharged Polysaccharide That Forms Hydrated
Structure and Function of the Plant CellGels
915
Wall
93 8
HA Inhibits Cell-Cell Adhesion and Facilitates
Cellulose Molecules Form Long, Rigi dCell Migration
916
Microfibrils
93 9
Proteoglycans Comprise a Diverse Family of
Other Polysaccharides Bind to Cellulose t oCell-surface and Extracellular Matrix
Generate a Complex Wall Matrix of Man yMacromolecules
916
Layers
940
Cartilage Proteoglycans Impart Resilience to
Cell Walls Contain Lignin and an Extended ,the Tissue
919
Hydroxyproline-rich Glycoprotein
942
The Orientation of Newly Made Cellulose
Oncogenic Transducing Retroviruses ContainMicrofibrils Is Affected by the Microtubule
Oncogenes Derived from Cellular Proto-Network
943
oncogenes
974
Remodeling of the Cell Wall Allows
Nononcogenic Transducing Retroviruses Hav eFormation of Specialized Structures
944
Been Constructed Experimentally
976
Cell-wall Oligosaccharides Act as Signaling
Slow-acting Carcinogenic Retroviruses Ca nAgents
944
Activate Nearby Cellular Proto-oncogene s
Summary
946
after Integration into the Host-cell Genome
976
References
947
Human Tumor Viruses
978
Chemical Carcinogens
980
Most Chemical Carcinogens Must Underg ov v
Metabolic Conversion to Become Active
981
The Carcinogenic Effect of Chemical s
T
Depends on Their Interaction with DNA
982
I'AR I IV
The Role of Radiation and DNA Repair in
The New Biology: Facing
Carcinogenesis
98 3
Classic Questions at the Frontier
953
Ineffective or Error-prone Repair of Damage d
24
DNA Perpetuates Mutations
983
CHAPTER 24 Cancer
955
Some Defects in DNA-repair Systems Ar eAssociated with High Cancer Rates i n
Characteristics of Tumor Cells
956
Humans
984
Malignant Tumor Cells Are Invasive and Can
Oncogenes and Their Proteins: Classificatio n
Spread
956
and Characteristics
984
Alterations in Cell-to-Cell Interactions Are
Four Types of Proteins Participate in Cel l
Associated with Malignancy
958
Growth
984
Tumor Cells Lack Normal Controls on Cell
Oncogene Proteins Affect the Cell's Growth -
Growth
959
control Systems in Various Ways
985
Use of Cell Cultures in Cancer Research
960
All Oncogenes Probably Are Derived fro mGrowth-controlling Genes
990Fibroblastic, Epithelial, and NonadherentCells Grow Readily in Culture
960
The Role of Cellular Oncogenes i n
Some Cell Cultures Give Rise to Immortal
Carcinogenesis
990
Cell Lines
961
Some, but Not All, Human Tumors Contai n
Certain Factors in Serum Are Required for
Cellular Oncogenes
990
Long-term Growth of Cultured Cells
962
Products of Cellular Oncogenes Act
Transformation Leads to Many
Cooperatively in Transformation and Tumo rMalignant
Induction
990Changes in Cultured Cells
963
Transcription of Oncogenes Can Trigger
Consistent Chromosomal Anomalie s
Transformation
967
Associated with Tumors Involve Oncogenes
992T f
DNA Viruses as Transforming Agents
967
The Multicausal, Multistep Nature ofCarcinogenesis
994DNA Viruses Can Transform Nonpermissive
EAlterations May Occur inCells by Random Integration of the Viral
TeratocarcinomasEpigeneti
c ti
994Genome into the Host-cell Genome
968
Transformation by DNA Viruses Requires
Some Cancer inducing Chemicals Act
Interaction of a Few Independently Acting
Synergistically
994
Viral Proteins
969
Natural Cancers Result from Interaction o f
RNA-containing Retroviruses as
Multiple Events over Time
995
Transforming Agents
971
Human Cancer
995
Productive Infection Cycle of Retroviruses
Rare Susceptibilities to Cancer Point t oInvolves Integration into Host-cell Genome
971
Antioncogenes
996
Summary
996
The Synthesis of Immunoglobulins Is Like
References
998
That of Other Extracellular Proteins
102 7
The Antigen-independent Phase ofB-lymphocyte Maturation
1028
B-lymphoid Cells Go Through an OrderlyCHAPTER 25 Immunity
1003
Process of Gene Rearrangement
1028
Overview
1004
The Antigen-independent Phase Can Generate10 11 Different Cell Types
102 8Antibodies Bind to Determinants and Have
The Immune System Requires AllelicTwo Functional Domains
1004
Exclusion
103 0Antibody Reaction with Antigen Is Reversible
1007
Antibody Gene Expression andAntibodies Come in Many Classes
1008
Rearrangement Is Controlled by Transcription
103 0
Antibodies Are Made by B Lymphocytes
1009
T Lymphocytes
103 1
The Immune System Has Extraordinary
There Are Two T-Cell Receptor Molecules
1032Plasticity
1009
T-Cell Receptors Recognize Foreign AntigensClonal Selection Theory Underlies All
as Compound Units with a Self-molecule
1032Modern Immunology
1010
The MHC Genes Were First Recognized inThe Immune System Has a Memory
1011
Tissue Transplantation Experiments
103 4
Other Parts of the Immune Response Are
T Cells Are Educated in the Thymus to Reac tCarried Out by T Lymphocytes
1013
with Foreign but Not Self-proteins
103 5
Macrophages Play a Central Role in
The Response of T Cells to Antigen Is EitherStimulating Immune Responses
1014
Cell Killing or Secretion of Protein Factors
103 7
Cells Responsible for the Immune Response
The Antigen-dependent Phase of the ImmuneCirculate throughout the Body
1014
Response
103 8
Tolerance Is a Central Concept of
Secretion by Activated B Cells Entails Man yImmunology
1016
Cellular Changes
104 1
Immunopathology Is Disease Caused by the
Secretion Requires Synthesis of an Altered HImmune System
1016
Chain
104 1
Antibodies and the Generation ofDiversity
1016
Two Cell Types Emerge from the Activation
Heavy-chain Structure Differentiates the
Process : Plasma Cells and Memory Cells
104 2
Classes of Antibodies
1017
Activation Leads to Synthesis of Secondary
Antibodies Have a Domain Structure
1017
Antibody Classes
1042
The N-Terminal Domains of H and L Chains
Somatic Mutation of Variable Regions
Have Highly Variable Structures That
Follows from Activation
1044
Constitute the Antigen-binding Site
1017
Tolerance Is Achieved Partly by Making B
Several Mechanisms Generate Antibody
Cells Unresponsive
1045
Diversity
1020
Summary
1045
DNA Rearrangement Generates Antibody
References
104 6Diversity
1022
A Single Recombination Event Generates
CHAPTER 26 Evolution of Cells
104 9Diversity in L Chains
102 2
Imprecision of Joining Makes an Important
Prebiotic Synthesis
105 1Contribution to Diversity
1023
Amino Acids and Nucleic Bases AreLambda Proteins Derive from Multiple
Prominent Products under Prebioti cConstant Regions
1026
Conditions
105 1
H-chain Variable Regions Derive from Three
RNA Probably Existed before DNA an dLibraries
1026
Protein
105 3
Recognition Sequences for All Joining
Prebiotic Synthesis of DNA RaisesReactions Are Highly Indistinguishable
1026
Unanswered Questions
1053
The Origin of the Genetic Code : Early RNA
Ribosomal RNA Comparisons Show ThreeProbably Interacted with Amino Acids and
Ancient Cell Lineages
106 4Peptides
1054
The Endosymbiont Hypothesis Is Confirme dPerfecting the Translation System Required
by rRNA Analysis
106 7More Complicated Structures in rRNA
1056
Evolution of Gene Structure: Lessons fromRNA Catalysis: A Basis for a Precellular
Present-Day Intron Distributions
106 8Genetic System?
1057
Nuclear Genes Illustrate the Loss of Introns
106 8Nuclease Activity Is the Simplest RNA
The Intron-Exon Structure of Genes Can B eCatalytic Event
1057
Stable for Very Long Times
106 9Self-splicing Can Remove Two Different
Do Exons Encode Protein Domains?
106 9Types of Introns
1058
RNA Polymerization, Site-specific Cleavage,
Are Actin and Tubulin Genes
and Ligation Can Be Carried Out by the
Counterexamples to Early Intron Existence?
107 1
Ribozyme from the Tetrahymena Group I
Already Recruited Domains Undergo ExonIntron
1060
Shuffling
107 1
RNA Editing May Be a Vestige of Precellular
The Origin of Cells : A Summary
1071Reactions
1061
Summary
1073Getting from RNA to DNA: Reverse
References
1074Transcriptase Is Widespread
1062
A Reconstructive Analysis of Cell Lineages
1063
Index
1077
