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Cover of Molecular Cell Biology

Molecular Cell Biology, 4th edition

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New York: W. H. Freeman; .
ISBN-10: 0-7167-3136-3

Excerpt

Modern biology is rooted in an understanding of the molecules within cells and of the interactions between cells that allow construction of multicellular organisms. The more we learn about the structure, function, and development of different organisms, the more we recognize that all life processes exhibit remarkable similarities. Molecular Cell Biology concentrates on the macromolecules and reactions studied by biochemists, the processes described by cell biologists, and the gene control pathways identified by molecular biologists and geneticists. In this millennium, two gathering forces will reshape molecular cell biology: genomics, the complete DNA sequence of many organisms, and proteomics, a knowledge of all the possible shapes and functions that proteins employ.

All the concepts of molecular cell biology continue to be derived from experiments, and powerful experimental tools that allow the study of living cells and organisms at higher and higher levels of resolution are being developed constantly. In this fourth edition, we address the current state of molecular cell biology and look forward to what further exploration will uncover in the twenty-first century.

Contents

  • About the Authors
  • Preface
  • Acknowledgments
  • Supplements
  • 1. The Dynamic Cell
    • 1.1. Evolution: At the Core of Molecular Change
    • 1.2. The Molecules of Life
    • 1.3. The Architecture of Cells
      • Cells Are Surrounded by Water-Impermeable Membranes
      • Membranes Serve Functions Other Than Segregation
      • Prokaryotes Comprise a Single Membrane-Limited Compartment
      • Eukaryotic Cells Contain Many Organelles and a Complex Cytoskeleton
      • Cellular DNA Is Packaged within Chromosomes
    • 1.4. The Life Cycle of Cells
      • The Cell Cycle Follows a Regular Timing Mechanism
      • Mitosis Apportions the Duplicated Chromosomes Equally to Daughter Cells
      • Cell Differentiation Creates New Types of Cells
      • Cells Die by Suicide
    • 1.5. Cells into Tissues
      • Multicellularity Requires Extracellular Glues
      • Tissues Are Organized into Organs
      • Body Plan and Rudimentary Tissues Form Early in Embryonic Development
    • 1.6. Molecular Cell Biology: An Integrated View of Cells at Work
  • 2. Chemical Foundations
    • 2.1. Covalent Bonds
      • Each Atom Can Make a Defined Number of Covalent Bonds
      • The Making or Breaking of Covalent Bonds Involves Large Energy Changes
      • Covalent Bonds Have Characteristic Geometries
      • Electrons Are Shared Unequally in Polar Covalent Bonds
      • Asymmetric Carbon Atoms Are Present in Most Biological Molecules
      • α and β Glycosidic Bonds Link Monosaccharides
      • SUMMARY
    • 2.2. Noncovalent Bonds
      • The Hydrogen Bond Underlies Water’s Chemical and Biological Properties
      • Ionic Interactions Are Attractions between Oppositely Charged Ions
      • Van der Waals Interactions Are Caused by Transient Dipoles
      • Hydrophobic Bonds Cause Nonpolar Molecules to Adhere to One Another
      • Multiple Noncovalent Bonds Can Confer Binding Specificity
      • Phospholipids Are Amphipathic Molecules
      • The Phospholipid Bilayer Forms the Basic Structure of All Biomembranes
      • SUMMARY
    • 2.3. Chemical Equilibrium
      • Equilibrium Constants Reflect the Extent of a Chemical Reaction
      • The Concentration of Complexes Can Be Estimated from Equilibrium Constants for Binding Reactions
      • Biological Fluids Have Characteristic pH Values
      • Hydrogen Ions Are Released by Acids and Taken Up by Bases
      • The Henderson-Hasselbalch Equation Relates pH and Keq of an Acid-Base System
      • Buffers Maintain the pH of Intracellular and Extracellular Fluids
      • SUMMARY
    • 2.4. Biochemical Energetics
      • Living Systems Use Various Forms of Energy, Which Are Interconvertible
      • The Change in Free Energy ΔG Determines the Direction of a Chemical Reaction
      • The ΔG of a Reaction Depends on Changes in Enthalpy (Bond Energy) and Entropy
      • Several Parameters Affect the ΔG of a Reaction
      • The ΔG°′ of a Reaction Can Be Calculated from Its Keq
      • Cells Must Expend Energy to Generate Concentration Gradients
      • Many Cellular Processes Involve Oxidation-Reduction Reactions
      • An Unfavorable Chemical Reaction Can Proceed If It Is Coupled with an Energetically Favorable Reaction
      • Hydrolysis of Phosphoanhydride Bonds in ATP Releases Substantial Free Energy
      • ATP Is Used to Fuel Many Cellular Processes
      • SUMMARY
    • 2.5. Activation Energy and Reaction Rate
      • Chemical Reactions Proceed through High-Energy Transition States
      • Enzymes Accelerate Biochemical Reactions by Reducing Transition-State Free Energy
      • SUMMARY
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Concept
      • Key Concept
      • Key Concept
    • References
      • General References
  • 3. Protein Structure and Function
    • 3.1. Hierarchical Structure of Proteins
      • The Amino Acids Composing Proteins Differ Only in Their Side Chains
      • Peptide Bonds Connect Amino Acids into Linear Chains
      • Four Levels of Structure Determine the Shape of Proteins
      • Graphic Representations of Proteins Highlight Different Features
      • Secondary Structures Are Crucial Elements of Protein Architecture
      • Motifs Are Regular Combinations of Secondary Structures
      • Structural and Functional Domains Are Modules of Tertiary Structure
      • Sequence Homology Suggests Functional and Evolutionary Relationships between Proteins
      • SUMMARY
    • 3.2. Folding, Modification, and Degradation of Proteins
      • The Information for Protein Folding Is Encoded in the Sequence
      • Folding of Proteins in Vivo Is Promoted by Chaperones
      • Chemical Modifications and Processing Alter the Biological Activity of Proteins
      • Cells Degrade Proteins via Several Pathways
      • Aberrantly Folded Proteins Are Implicated in Slowly Developing Diseases
      • SUMMARY
    • 3.3. Functional Design of Proteins
      • Proteins Are Designed to Bind a Wide Range of Molecules
      • Antibodies Exhibit Precise Ligand-Binding Specificity
      • Enzymes Are Highly Efficient and Specific Catalysts
      • An Enzyme’s Active Site Binds Substrates and Carries Out Catalysis
      • Kinetics of an Enzymatic Reaction Are Described by Vmax and Km
      • Many Proteins Contain Tightly Bound Prosthetic Groups
      • A Variety of Regulatory Mechanisms Control Protein Function
      • SUMMARY
    • 3.4. Membrane Proteins
      • Proteins Interact with Membranes in Different Ways
      • Hydrophobic α Helices in Transmembrane Proteins Are Embedded in the Bilayer
      • Many Integral Proteins Contain Multiple Transmembrane α Helices
      • Multiple β Strands in Porins Form Membrane-Spanning “Barrels”
      • Covalently Attached Hydrocarbon Chains Anchor Some Proteins to the Membrane
      • Some Peripheral Proteins Are Soluble Enzymes That Act on Membrane Components
      • SUMMARY
    • 3.5. Purifying, Detecting, and Characterizing Proteins
      • Proteins Can Be Removed from Membranes by Detergents or High-Salt Solutions
      • Centrifugation Can Separate Particles and Molecules That Differ in Mass or Density
      • Electrophoresis Separates Molecules according to Their Charge:Mass Ratio
      • Liquid Chromatography Resolves Proteins by Mass, Charge, or Binding Affinity
      • Highly Specific Enzyme and Antibody Assays Can Detect Individual Proteins
      • Radioisotopes Are Indispensable Tools for Detecting Biological Molecules
      • Protein Primary Structure Can Be Determined by Chemical Methods and from Gene Sequences
      • Time-of-Flight Mass Spectrometry Measures the Mass of Proteins and Peptides
      • Peptides with a Defined Sequence Can Be Synthesized Chemically
      • Protein Conformation Is Determined by Sophisticated Physical Methods
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Concept
      • Key Experiment
      • Key Application
    • References
      • General References
      • Web Sites
      • Hierarchical Structure of Proteins
      • Folding, Modification, and Degradation of Proteins
      • Functional Design of Proteins
      • Purifying, Detecting, and Characterizing Proteins
  • 4. Nucleic Acids, the Genetic Code, and the Synthesis of Macromolecules
    • 4.1. Structure of Nucleic Acids
      • Polymerization of Nucleotides Forms Nucleic Acids
      • Native DNA Is a Double Helix of Complementary Antiparallel Chains
      • DNA Can Undergo Reversible Strand Separation
      • Many DNA Molecules Are Circular
      • Local Unwinding of DNA Induces Supercoiling
      • RNA Molecules Exhibit Varied Conformations and Functions
      • SUMMARY
    • 4.2. Synthesis of Biopolymers: Rules of Macromolecular Carpentry
    • 4.3. Nucleic Acid Synthesis
      • Both DNA and RNA Chains Are Produced by Copying of Template DNA Strands
      • Nucleic Acid Strands Grow in the 5′ → 3′ Direction
      • RNA Polymerases Can Initiate Strand Growth but DNA Polymerases Cannot
      • Replication of Duplex DNA Requires Assembly of Many Proteins at a Growing Fork
      • Organization of Genes in DNA Differs in Prokaryotes and Eukaryotes
      • Eukaryotic Primary RNA Transcripts Are Processed to Form Functional mRNAs
      • SUMMARY
    • 4.4. The Three Roles of RNA in Protein Synthesis
      • Messenger RNA Carries Information from DNA in a Three-Letter Genetic Code
      • Experiments with Synthetic mRNAs and Trinucleotides Broke the Genetic Code
      • The Folded Structure of tRNA Promotes Its Decoding Functions
      • Nonstandard Base Pairing Often Occurs between Codons and Anticodons
      • Aminoacyl-tRNA Synthetases Activate Amino Acids by Linking Them to tRNAs
      • Each tRNA Molecule Is Recognized by a Specific Aminoacyl-tRNA Synthetase
      • Ribosomes Are Protein-Synthesizing Machines
      • SUMMARY
    • 4.5. Stepwise Formation of Proteins on Ribosomes
      • The AUG Start Codon Is Recognized by Methionyl-tRNAiMet
      • Bacterial Initiation of Protein Synthesis Begins Near a Shine-Dalgarno Sequence in mRNA
      • Eukaryotic Initiation of Protein Synthesis Occurs at the 5′ End and Internal Sites in mRNA
      • During Chain Elongation Each Incoming Aminoacyl-tRNA Moves through Three Ribosomal Sites
      • Protein Synthesis Is Terminated by Release Factors When a Stop Codon Is Reached
      • Simultaneous Translation by Multiple Ribosomes and Their Rapid Recycling Increase the Efficiency of Protein Synthesis
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
      • References
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Concept
      • Key Experiment
      • Key Application
    • References
      • General References
      • Nucleic Acids: Structure and General Properties
      • Nucleic Acid Synthesis
      • The Genetic Code
      • Initiation
      • Transfer RNA and Amino Acids
      • Ribosomes
      • The Steps in Protein Synthesis
  • 5. Biomembranes and the Subcellular Organization of Eukaryotic Cells
    • 5.1. Microscopy and Cell Architecture
      • Light Microscopy Can Distinguish Objects Separated by 0.2 μm or More
      • Samples for Light Microscopy Usually Are Fixed, Sectioned, and Stained
      • Fluorescence Microscopy Can Localize and Quantify Specific Molecules in Cells
      • Confocal Scanning and Deconvolution Microscopy Provide Sharper Images of Three-Dimensional Objects
      • Phase-Contrast and Nomarski Interference Microscopy Visualize Unstained Living Cells
      • Transmission Electron Microscopy Has a Limit of Resolution of 0.1 nm
      • Scanning Electron Microscopy Visualizes Details on the Surfaces of Cells and Particles
      • SUMMARY
    • 5.2. Purification of Cells and Their Parts
      • Flow Cytometry Separates Different Cell Types
      • Disruption of Cells Releases Their Organelles and Other Contents
      • Different Organelles Can Be Separated by Centrifugation
      • Organelle-Specific Antibodies Are Useful in Preparing Highly Purified Organelles
      • SUMMARY
    • 5.3. Biomembranes: Structural Organization and Basic Functions
      • Phospholipids Are the Main Lipid Constituents of Most Biomembranes
      • Every Cellular Membrane Forms a Closed Compartment and Has a Cytosolic and an Exoplasmic Face
      • Several Types of Evidence Point to the Universality of the Phospholipid Bilayer
      • All Integral Proteins and Glycolipids Bind Asymmetrically to the Lipid Bilayer
      • The Phospholipid Composition Differs in Two Membrane Leaflets
      • Most Lipids and Integral Proteins Are Laterally Mobile in Biomembranes
      • Fluidity of Membranes Depends on Temperature and Composition
      • Membrane Leaflets Can Be Separated and Each Face Viewed Individually
      • The Plasma Membrane Has Many Common Functions in All Cells
      • SUMMARY
    • 5.4. Organelles of the Eukaryotic Cell
      • Lysosomes Are Acidic Organelles That Contain a Battery of Degradative Enzymes
      • Plant Vacuoles Store Small Molecules and Enable the Cell to Elongate Rapidly
      • Peroxisomes Degrade Fatty Acids and Toxic Compounds
      • Mitochondria Are the Principal Sites of ATP Production in Aerobic Cells
      • Chloroplasts, the Sites of Photosynthesis, Contain Three Membrane-Limited Compartments
      • The Endoplasmic Reticulum Is a Network of Interconnected Internal Membranes
      • Golgi Vesicles Process and Sort Secretory and Membrane Proteins
      • The Double-Membraned Nucleus Contains the Nucleolus and a Fibrous Matrix
      • The Cytosol Contains Many Particles and Cytoskeletal Fibers
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
      • References
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Concept
      • Key Experiment
      • Key Application
    • References
      • Light Microscopy
      • Electron Microscopy
      • Cell Structure: Histology Texts and Atlases
      • Purification of Cells and Their Parts
      • Biomembranes: Structural Organization and Basic Functions
      • Organelles of the Eukaryotic Cell
  • 6. Manipulating Cells and Viruses in Culture
    • 6.1. Growth of Microorganisms in Culture
      • Many Microorganisms Can Be Grown in Minimal Medium
      • Mutant Strains of Bacteria and Yeast Can Be Isolated by Replica Plating
      • SUMMARY
    • 6.2. Growth of Animal Cells in Culture
      • Rich Media Are Required for Culture of Animal Cells
      • Most Cultured Animal Cells Grow Only on Special Solid Surfaces
      • Primary Cell Cultures Are Useful, but Have a Finite Life Span
      • Transformed Cells Can Grow Indefinitely in Culture
      • Fusion of Cultured Animal Cells Can Yield Interspecific Hybrids Useful in Somatic-Cell Genetics
      • Hybrid Cells Often Are Selected on HAT Medium
      • Hybridomas Are Used to Produce Monoclonal Antibodies
      • SUMMARY
    • 6.3. Viruses: Structure, Function, and Uses
      • Viral Capsids Are Regular Arrays of One or a Few Types of Protein
      • Most Viral Host Ranges Are Narrow
      • Viruses Can Be Cloned and Counted in Plaque Assays
      • Viral Growth Cycles Are Classified as Lytic or Lysogenic
      • Four Types of Bacterial Viruses Are Widely Used in Biochemical and Genetic Research
      • Animal Viruses Are Classified by Genome Type and mRNA Synthesis Pathway
      • Viral Vectors Can Be Used to Introduce Specific Genes into Cells
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
      • References
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Concept
      • Key Experiment
      • Key Application
    • References
      • Growth of Microorganisms in Culture
      • Growth of Animal Cells in Culture
      • Viruses: Structure, Function, and Uses
  • 7. Recombinant DNA and Genomics
    • 7.1. DNA Cloning with Plasmid Vectors
      • Plasmids Are Extrachromosomal Self-Replicating DNA Molecules
      • E. Coli Plasmids Can Be Engineered for Use as Cloning Vectors
      • Plasmid Cloning Permits Isolation of DNA Fragments from Complex Mixtures
      • Restriction Enzymes Cut DNA Molecules at Specific Sequences
      • Restriction Fragments with Complementary “Sticky Ends” Are Ligated Easily
      • Polylinkers Facilitate Insertion of Restriction Fragments into Plasmid Vectors
      • Small DNA Molecules Can Be Chemically Synthesized
      • SUMMARY
    • 7.2. Constructing DNA Libraries with λ Phage and Other Cloning Vectors
      • Bacteriophage λ Can Be Modified for Use as a Cloning Vector and Assembled in Vitro
      • Nearly Complete Genomic Libraries of Higher Organisms Can Be Prepared by λ Cloning
      • cDNA Libraries Are Prepared from Isolated mRNAs
      • Larger DNA Fragments Can Be Cloned in Cosmids and Other Vectors
      • SUMMARY
    • 7.3. Identifying, Analyzing, and Sequencing Cloned DNA
      • Libraries Can Be Screened with Membrane-Hybridization Assay
      • Oligonucleotide Probes Are Designed Based on Partial Protein Sequences
      • Specific Clones Can Be Identified Based on Properties of the Encoded Proteins
      • Gel Electrophoresis Resolves DNA Fragments of Different Size
      • Multiple Restriction Sites Can Be Mapped on a Cloned DNA Fragment
      • Pulsed-Field Gel Electrophoresis Separates Large DNA Molecules
      • Purified DNA Molecules Can Be Sequenced Rapidly by Two Methods
      • SUMMARY
    • 7.4. Bioinformatics
      • Stored Sequences Suggest Functions of Newly Identified Genes and Proteins
      • Comparative Analysis of Genomes Reveals Much about an Organism’s Biology
      • Homologous Proteins Involved in Genetic Information Processing Are Widely Distributed
      • Many Yeast Genes Function in Intracellular Protein Targeting and Secretion
      • The C. elegans Genome Encodes Numerous Proteins Specific to Multicellular Organisms
      • SUMMARY
    • 7.5. Analyzing Specific Nucleic Acids in Complex Mixtures
      • Southern Blotting Detects Specific DNA Fragments
      • Northern Blotting Detects Specific RNAs
      • Specific RNAs Can Be Quantitated and Mapped on DNA by Nuclease Protection
      • Transcription Start Sites Can Be Mapped by S1 Protection and Primer Extension
      • SUMMARY
    • 7.6. Producing High Levels of Proteins from Cloned cDNAs
      • E. coli Expression Systems Can Produce Full-Length Proteins
      • Eukaryotic Expression Systems Can Produce Proteins with Post-Translational Modifications
      • Cloned cDNAs Can Be Translated in Vitro to Yield Labeled Proteins
      • SUMMARY
    • 7.7. Polymerase Chain Reaction: An Alternative to Cloning
      • PCR Amplification of Mutant Alleles Permits Their Detection in Small Samples
      • DNA Sequences Can Be Amplified for Use in Cloning and as Probes
      • SUMMARY
    • 7.8. DNA Microarrays: Analyzing Genome-Wide Expression
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
      • References
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Experiment
      • Key Application
      • Key Experiment
    • References
      • DNA Cloning with Plasmid Vectors
      • Constructing DNA Libraries with λ Phage and Other Cloning Vectors
      • Identifying, Analyzing, and Sequencing Cloned DNA
      • Bioinformatics
      • Analyzing Specific Nucleic Acids in Complex Mixtures
      • Producing High Levels of Proteins from Cloned cDNAs
      • Polymerase Chain Reaction: An Alternative to Cloning
      • DNA Microarrays: Analyzing Genome-wide Expression
  • 8. Genetic Analysis in Cell Biology
    • 8.1. Mutations: Types and Causes
      • Mutations Are Recessive or Dominant
      • Inheritance Patterns of Recessive and Dominant Mutations Differ
      • Mutations Involve Large or Small DNA Alterations
      • Mutations Occur Spontaneously and Can Be Induced
      • Some Human Diseases Are Caused by Spontaneous Mutations
      • SUMMARY
    • 8.2. Isolation and Analysis of Mutants
      • Temperature-Sensitive Screens Can Isolate Lethal Mutations in Haploids
      • Recessive Lethal Mutations in Diploids Can Be Screened by Use of Visible Markers
      • Complementation Analysis Determines If Different Mutations Are in the Same Gene
      • Metabolic and Other Pathways Can Be Genetically Dissected
      • Suppressor Mutations Can Identify Genes Encoding Interacting Proteins
      • SUMMARY
    • 8.3. Genetic Mapping of Mutations
      • Segregation Patterns Indicate Whether Mutations Are on the Same or Different Chromosomes
      • Chromosomal Mapping Locates Mutations on Particular Chromosomes
      • Recombinational Analysis Can Map Genes Relative to Each Other on a Chromosome
      • DNA Polymorphisms Are Used to Map Human Mutations
      • Some Chromosomal Abnormalities Can Be Mapped by Banding Analysis
      • SUMMARY
    • 8.4. Molecular Cloning of Genes Defined by Mutations
      • Cloned DNA Segments Near a Gene of Interest Are Identified by Various Methods
      • Chromosome Walking Is Used to Isolate a Limited Region of Contiguous DNA
      • Physical Maps of Entire Chromosomes Can Be Constructed by Screening YAC Clones for Sequence-Tagged Sites
      • Physical and Genetic Maps Can Be Correlated with the Aid of Known Markers
      • Further Analysis Is Needed to Locate a Mutation-Defined Gene in Cloned DNA
      • Protein Structure Is Deduced from cDNA Sequence
      • SUMMARY
    • 8.5. Gene Replacement and Transgenic Animals
      • Specific Sites in Cloned Genes Can Be Altered in Vitro
      • DNA Is Transferred into Eukaryotic Cells in Various Ways
      • Normal Genes Can Be Replaced with Mutant Alleles in Yeast and Mice
      • Foreign Genes Can Be Introduced into Plants and Animals
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
      • References
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Concept
      • Key Experiment
      • Key Application
    • References
      • Mutations: Types and Causes
      • Isolation and Analysis of Mutants
      • Genetic Mapping of Mutations
      • Molecular Cloning of Genes Defined by Mutations
      • Gene Replacement and Transgenic Animals
  • 9. Molecular Structure of Genes and Chromosomes
    • 9.1. Molecular Definition of a Gene
      • Bacterial Operons Produce Polycistronic mRNAs
      • Most Eukaryotic mRNAs Are Monocistronic and Contain Introns
      • Simple and Complex Transcription Units Are Found in Eukaryotic Genomes
      • SUMMARY
    • 9.2. Chromosomal Organization of Genes and Noncoding DNA
      • Genomes of Higher Eukaryotes Contain Much Nonfunctional DNA
      • Cellular DNA Content Does Not Correlate with Phylogeny
      • Protein-Coding Genes May Be Solitary or Belong to a Gene Family
      • Tandemly Repeated Genes Encode rRNAs, tRNAs, and Histones
      • Reassociation Experiments Reveal Three Major Fractions of Eukaryotic DNA
      • Simple-Sequence DNAs Are Concentrated in Specific Chromosomal Locations
      • DNA Fingerprinting Depends on Differences in Length of Simple-Sequence DNAs
      • SUMMARY
    • 9.3. Mobile DNA
      • Movement of Mobile Elements Involves a DNA or RNA Intermediate
      • Mobile Elements That Move as DNA Are Present in Prokaryotes and Eukaryotes
      • Viral Retrotransposons Contain LTRs and Behave Like Retroviruses in the Genome
      • Nonviral Retrotransposons Lack LTRs and Move by an Unusual Mechanism
      • Retrotransposed Copies of Cellular RNAs Occur in Eukaryotic Chromosomes
      • Mobile DNA Elements Probably Had a Significant Influence on Evolution
      • SUMMARY
    • 9.4. Functional Rearrangements in Chromosomal DNA
      • Inversion of a Transcription-Control Region Switches Salmonella Flagellar Antigens
      • Antibody Genes Are Assembled by Rearrangements of Germ-Line DNA
      • Generalized DNA Amplification Produces Polytene Chromosomes
      • SUMMARY
    • 9.5. Organizing Cellular DNA into Chromosomes
      • Most Bacterial Chromosomes Are Circular with One Replication Origin
      • Eukaryotic Nuclear DNA Associates with Histone Proteins to Form Chromatin
      • Chromatin Exists in Extended and Condensed Forms
      • Acetylation of Histone N-Termini Reduces Chromatin Condensation
      • Eukaryotic Chromosomes Contain One Linear DNA Molecule
      • SUMMARY
    • 9.6. Morphology and Functional Elements of Eukaryotic Chromosomes
      • Chromosome Number, Size, and Shape at Metaphase Are Species Specific
      • Nonhistone Proteins Provide a Structural Scaffold for Long Chromatin Loops
      • Chromatin Contains Small Amounts of Other Proteins in Addition to Histones and Scaffold Proteins
      • Stained Chromosomes Have Characteristic Banding Patterns
      • Chromosome Painting Distinguishes Each Homologous Pair by Color
      • Heterochromatin Consists of Chromosome Regions That Do Not Uncoil
      • Three Functional Elements Are Required for Replication and Stable Inheritance of Chromosomes
      • Yeast Artificial Chromosomes Can Be Used to Clone Megabase DNA Fragments
      • SUMMARY
    • 9.7. Organelle DNAs
      • Mitochondria Contain Multiple mtDNA Molecules
      • Genes in mtDNA Exhibit Cytoplasmic Inheritance and Encode rRNAs, tRNAs, and Some Mitochondrial Proteins
      • The Size and Coding Capacity of mtDNA Vary Considerably in Different Organisms
      • Products of Mitochondrial Genes Are Not Exported
      • Mitochondrial Genetic Codes Differ from the Standard Nuclear Code
      • Mutations in Mitochondrial DNA Cause Several Genetic Diseases in Man
      • Chloroplasts Contain Large Circular DNAs Encoding More Than a Hundred Proteins
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
      • References
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Experiment
      • Key Application
      • Key Concept
    • References
      • Chromosomal Organization of Genes and Noncoding DNA
      • Mobile DNA
      • Functional Rearrangements in Chromosomal DNA
      • Organizing Cellular DNA into Chromosomes
      • Morphology and Functional Elements of Eukaryotic Chromosomes
      • Organelle DNAs
  • 10. Regulation of Transcription Initiation
    • 10.1. Bacterial Gene Control: The Jacob-Monod Model
      • Enzymes Encoded at the lac Operon Can Be Induced and Repressed
      • Mutations in lacI Cause Constitutive Expression of lac Operon
      • Isolation of Operator Constitutive and Promoter Mutants Support Jacob-Monod Model
      • Regulation of lac Operon Depends on Cis-Acting DNA Sequences and Trans-Acting Proteins
      • Biochemical Experiments Confirm That Induction of the lac Operon Leads to Increased Synthesis of lac mRNA
      • SUMMARY
    • 10.2. Bacterial Transcription Initiation
      • Footprinting and Gel-Shift Assays Identify Protein-DNA Interactions
      • The lac Control Region Contains Three Critical Cis-Acting Sites
      • RNA Polymerase Binds to Specific Promoter Sequences to Initiate Transcription
      • Differences in E. coli Promoter Sequences Affect Frequency of Transcription Initiation
      • Binding of lac Repressor to the lac Operator Blocks Transcription Initiation
      • Most Bacterial Repressors Are Dimers Containing α Helices That Insert into Adjacent Major Grooves of Operator DNA
      • Ligand-Induced Conformational Changes Alter Affinity of Many Repressors for DNA
      • Positive Control of the lac Operon Is Exerted by cAMP-CAP
      • Cooperative Binding of cAMP-CAP and RNA Polymerase to lac Control Region Activates Transcription
      • Transcription Control at All Bacterial Promoters Involves Similar but Distinct Mechanisms
      • Transcription from Some Promoters Is Initiated by Alternative Sigma (σ) Factors
      • Many Bacterial Responses Are Controlled by Two-Component Regulatory Systems
      • SUMMARY
    • 10.3. Eukaryotic Gene Control: Purposes and General Principles
      • Most Genes in Higher Eukaryotes Are Regulated by Controlling Their Transcription
      • Regulatory Elements in Eukaryotic DNA Often Are Many Kilobases from Start Sites
      • Three Eukaryotic Polymerases Catalyze Formation of Different RNAs
      • The Largest Subunit in RNA Polymerase II Has an Essential Carboxyl-Terminal Repeat
      • RNA Polymerase II Initiates Transcription at DNA Sequences Corresponding to the 5′ Cap of mRNAs
      • SUMMARY
    • 10.4. Regulatory Sequences in Eukaryotic Protein-Coding Genes
      • TATA Box, Initiators, and CpG Islands Function as Promoters in Eukaryotic DNA
      • Promoter-Proximal Elements Help Regulate Eukaryotic Genes
      • Transcription by RNA Polymerase II Often Is Stimulated by Distant Enhancer Sites
      • Most Eukaryotic Genes Are Regulated by Multiple Transcription-Control Elements
      • SUMMARY
    • 10.5. Eukaryotic Transcription Activators and Repressors
      • Biochemical and Genetic Techniques Have Been Used to Identify Transcription Factors
      • Transcription Activators Are Modular Proteins Composed of Distinct Functional Domains
      • DNA-Binding Domains Can Be Classified into Numerous Structural Types
      • Heterodimeric Transcription Factors Increase Gene-Control Options
      • Activation Domains Exhibit Considerable Structural Diversity
      • Multiprotein Complexes Form on Enhancers
      • Many Repressors Are the Functional Converse of Activators
      • SUMMARY
    • 10.6. RNA Polymerase II Transcription-Initiation Complex
      • Initiation by Pol II Requires General Transcription Factors
      • Proteins Comprising the Pol II Transcription-Initiation Complex Assemble in a Specific Order in Vitro
      • A Pol II Holoenzyme Multiprotein Complex Functions in Vivo
      • SUMMARY
    • 10.7. Molecular Mechanisms of Eukaryotic Transcriptional Control
      • N-Termini of Histones in Chromatin Can Be Modified
      • Formation of Heterochromatin Silences Gene Expression at Telomeres and Other Regions
      • Repressors Can Direct Histone Deacetylation at Specific Genes
      • Activators Can Direct Histone Acetylation at Specific Genes
      • Chromatin-Remodeling Factors Participate in Activation at Some Promoters
      • Activators Stimulate the Highly Cooperative Assembly of Initiation Complexes
      • Repressors Interfere Directly with Transcription Initiation in Several Ways
      • Regulation of Transcription-Factor Expression Contributes to Gene Control
      • Lipid-Soluble Hormones Control the Activities of Nuclear Receptors
      • Polypeptide Hormones Signal Phosphorylation of Some Transcription Factors
      • SUMMARY
    • 10.8. Other Transcription Systems
      • Transcription Initiation by Pol I and Pol III Is Analogous to That by Pol II
      • T7 and Related Bacteriophages Express Monomeric, Largely Unregulated RNA Polymerases
      • Mitochondrial DNA Is Transcribed by RNA Polymerases with Similarities to Bacteriophage and Bacterial Enzymes
      • Transcription of Chloroplast DNA Resembles Bacterial Transcription
      • Transcription by Archaeans Is Closer to Eukaryotic Than to Bacterial Transcription
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
      • References
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Concept
      • Key Experiment
      • Key Application
    • References
      • Bacterial Gene Control: The Jacob-Monod Model
      • Bacterial Transcription Initiation
      • Eukaryotic Gene Control: Purposes and General Principles
      • Regulatory Sequences in Eukaryotic Protein-Coding Genes
      • Eukaryotic Transcription Activators and Repressor
      • RNA Polymerase II Transcription-Initiation Complex
      • Molecular Mechanisms of Eukaryotic Transcription Control
      • Other Transcription Systems
  • 11. RNA Processing, Nuclear Transport, and Post-Transcriptional Control
    • 11.1. Transcription Termination
      • Rho-Independent Termination Occurs at Characteristic Sequences in E. coli DNA
      • Premature Termination by Attenuation Helps Regulate Expression of Some Bacterial Operons
      • Rho-Dependent Termination Sites Are Present in Some λ-Phage and E. coli Genes
      • Sequence-Specific RNA-Binding Proteins Can Regulate Termination by E. coli RNA Polymerase
      • Three Eukaryotic RNA Polymerases Employ Different Termination Mechanisms
      • Transcription of HIV Genome Is Regulated by an Antitermination Mechanism
      • Promoter-Proximal Pausing of RNA Polymerase II Occurs in Some Rapidly Induced Genes
      • SUMMARY
    • 11.2. Processing of Eukaryotic mRNA
      • The 5′-Cap Is Added to Nascent RNAs Shortly after Initiation by RNA Polymerase II
      • Pre-mRNAs Are Associated with hnRNP Proteins Containing Conserved RNA-Binding Domains
      • hnRNP Proteins May Assist in Processing and Transport of mRNAs
      • Pre-mRNAs Are Cleaved at Specific 3′ Sites and Rapidly Polyadenylated
      • Splicing Occurs at Short, Conserved Sequences in Pre-mRNAs via Two Transesterification Reactions
      • Spliceosomes, Assembled from snRNPs and a Pre-mRNA, Carry Out Splicing
      • Portions of Two Different RNAs Are Trans-Spliced in Some Organisms
      • Self-Splicing Group II Introns Provide Clues to the Evolution of snRNAs
      • Most Transcription and RNA Processing Occur in a Limited Number of Domains in Mammalian Cell Nuclei
      • SUMMARY
    • 11.3. Regulation of mRNA Processing
      • U1A Protein Inhibits Polyadenylation of Its Pre-mRNA
      • Tissue-Specific RNA Splicing Controls Expression of Alternative Fibronectins
      • A Cascade of Regulated RNA Splicing Controls Drosophila Sexual Differentiation
      • Multiple Protein Isoforms Are Common in the Vertebrate Nervous System
      • SUMMARY
    • 11.4. Signal-Mediated Transport through Nuclear Pore Complexes
      • Nuclear Pore Complexes Actively Transport Macromolecules between the Nucleus and Cytoplasm
      • Receptors for Nuclear-Export Signals Transport Proteins and mRNPs out of the Nucleus
      • Pre-mRNAs in Spliceosomes Are Not Exported from the Nucleus
      • Receptors for Nuclear-Localization Signals Transport Proteins into the Nucleus
      • Various Nuclear-Transport Systems Utilize Similar Proteins
      • HIV Rev Protein Regulates the Transport of Unspliced Viral mRNAs
      • SUMMARY
    • 11.5. Other Mechanisms of Post-Transcriptional Control
      • RNA Editing Alters the Sequences of Pre-mRNAs
      • Some mRNAs Are Associated with Cytoplasmic Structures or Localized to Specific Regions
      • Stability of Cytoplasmic mRNAs Varies Widely
      • Degradation Rate of Some Eukaryotic mRNAs Is Regulated
      • Translation of Some mRNAs Is Regulated by Specific RNA-Binding Proteins
      • Antisense RNA Regulates Translation of Transposase mRNA in Bacteria
      • SUMMARY
    • 11.6. Processing of rRNA and tRNA
      • Pre-rRNA Genes Are Similar in All Eukaryotes and Function as Nucleolar Organizers
      • Small Nucleolar RNAs (snoRNAs) Assist in Processing rRNAs and Assembling Ribosome Subunits
      • Self-Splicing Group I Introns Were the First Examples of Catalytic RNA
      • All Pre-tRNAs Undergo Cleavage and Base Modification
      • Splicing of Pre-tRNAs Differs from Other Splicing Mechanisms
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
      • References
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Application
      • Key Experiment
      • Key Concept
    • References
      • Transcription Termination
      • Processing of Eukaryotic mRNA
      • Regulation of mRNA Processing
      • Signal-Mediated Transport through Nuclear Pore Complexes
      • Other Mechanisms of Post-Transcriptional Control
      • Processing of rRNA and tRNA
  • 12. DNA Replication, Repair, and Recombination
    • 12.1. General Features of Chromosomal Replication
      • DNA Replication Is Semiconservative
      • Most DNA Replication Is Bidirectional
      • DNA Replication Begins at Specific Chromosomal Sites
      • SUMMARY
    • 12.2. The DNA Replication Machinery
      • DnaA Protein Initiates Replication in E. coli
      • DnaB Is an E. coli Helicase That Melts Duplex DNA
      • E. coli Primase Catalyzes Formation of RNA Primers for DNA Synthesis
      • At a Growing Fork One Strand Is Synthesized Discontinuously from Multiple Primers
      • E. coli DNA Polymerase III Catalyzes Nucleotide Addition at the Growing Fork
      • The Leading and Lagging Strands Are Synthesized Concurrently
      • Eukaryotic Replication Machinery Is Generally Similar to That of E. coli
      • Telomerase Prevents Progressive Shortening of Lagging Strands during Eukaryotic DNA Replication
      • SUMMARY
    • 12.3. The Role of Topoisomerases in DNA Replication
      • Type I Topoisomerases Relax DNA by Nicking and Then Closing One Strand of Duplex DNA
      • Type II Topoisomerases Change DNA Topology by Breaking and Rejoining Double-Stranded DNA
      • Replicated Circular DNA Molecules Are Separated by Type II Topoisomerases
      • Linear Daughter Chromatids Also Are Separated by Type II Topoisomerases
      • SUMMARY
    • 12.4. DNA Damage and Repair and Their Role in Carcinogenesis
      • Proofreading by DNA Polymerase Corrects Copying Errors
      • Chemical Carcinogens React with DNA Directly or after Activation
      • The Carcinogenic Effect of Chemicals Correlates with Their Mutagenicity
      • DNA Damage Can Be Repaired by Several Mechanisms
      • Eukaryotes Have DNA-Repair Systems Analogous to Those of E. coli
      • Inducible DNA-Repair Systems Are Error-Prone
      • SUMMARY
    • 12.5. Recombination between Homologous DNA Sites
      • The Crossed-Strand Holliday Structure Is an Intermediate in Recombination
      • Double-Strand Breaks in DNA Initiate Recombination
      • The Activities of E. coli Recombination Proteins Have Been Determined
      • Cre Protein and Other Recombinases Catalyze Site-Specific Recombination
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
      • References
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Application
      • Key Concept
      • Key Experiment
    • References
      • General Features of Chromosomal Replication
      • The DNA Replication Machinery
      • Role of Topoisomerases in DNA Replication
      • DNA Damage and Repair and Their Role in Carcinogenesis
      • Recombination between Homologous DNA Sites
  • 13. Regulation of the Eukaryotic Cell Cycle
    • 13.1. Overview of the Cell Cycle and Its Control
      • The Cell Cycle Is an Ordered Series of Events Leading to Replication of Cells
      • Regulated Protein Phosphorylation and Degradation Control Passage through the Cell Cycle
      • Diverse Experimental Systems Have Been Used to Identify and Isolate Cell-Cycle Control Proteins
      • SUMMARY
    • 13.2. Biochemical Studies with Oocytes, Eggs, and Early Embryos
      • MPF Promotes Maturation of Oocytes and Mitosis in Somatic Cells
      • Mitotic Cyclin Was First Identified in Early Sea Urchin Embryos
      • Cyclin B Levels and MPF Activity Change Together in Cycling Xenopus Egg Extracts
      • Ubiquitin-Mediated Degradation of Mitotic Cyclins Promotes Exit from Mitosis
      • Regulation of APC Activity Controls Degradation of Cyclin B
      • SUMMARY
    • 13.3. Genetic Studies with S. pombe
      • Two Classes of Mutations in S. pombe Produce Either Elongated or Very Small Cells
      • S. pombe Cdc2 - Cdc13 Heterodimer Is Equivalent to Xenopus MPF
      • Phosphorylation of the Catalytic Subunit Regulates MPF Kinase Activity
      • Conformational Changes Induced by Cyclin Binding and Phosphorylation Increase MPF Activity
      • Other Mechanisms Also Control Entry into Mitosis by Regulating MPF Activity
      • SUMMARY
    • 13.4. Molecular Mechanisms for Regulating Mitotic Events
      • Phosphorylation of Nuclear Lamins by MPF Leads to Nuclear-Envelope Breakdown
      • Other Early Mitotic Events May Be Controlled Directly or Indirectly by MPF
      • APC-Dependent Unlinking of Sister Chromatids Initiates Anaphase
      • Phosphatase Activity Is Required for Reassembly of the Nuclear Envelope and Cytokinesis
      • SUMMARY
    • 13.5. Genetic Studies with S. cerevisiae
      • S. cerevisiae Cdc28 Is Functionally Equivalent to S. pombe Cdc2
      • Three G1 Cyclins Associate with Cdc28 to form S Phase – Promoting Factors
      • Kinase Activity of Cdc28 – G1 Cyclin Complexes Prepares Cells for the S Phase
      • Degradation of the S-Phase Inhibitor Sic1 Triggers DNA Replication
      • Multiple Cyclins Direct Kinase Activity of Cdc28 during Different Cell-Cycle Phases
      • Replication at Each Origin Is Initiated Only Once during the Cell Cycle
      • SUMMARY
    • 13.6. Cell-Cycle Control in Mammalian Cells
      • Mammalian Restriction Point is Analogous to start in Yeast Cells
      • Multiple Cdks and Cyclins Regulate Passage of Mammalian Cells through the Cell Cycle
      • Regulated Expression of Two Classes of Genes Returns G0 Mammalian Cells to the Cell Cycle
      • Passage through the Restriction Point Depends on Activation of E2F Transcription Factors
      • Cyclin A Is Required for DNA Synthesis and Cdk1 for Entry into Mitosis
      • Mammalian Cyclin-Kinase Inhibitors Contribute to Cell-Cycle Control
      • SUMMARY
    • 13.7. Checkpoints in Cell-Cycle Regulation
      • The Presence of Unreplicated DNA Prevents Entry into Mitosis
      • Improper Assembly of the Mitotic Spindle Leads to Arrest in Anaphase
      • G1 and G2 Arrest in Cells with Damaged DNA Depends on a Tumor Suppressor and Cyclin-Kinase Inhibitor
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
      • References
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Concept
      • Key Experiment
      • Key Application
    • References
      • Overview of the Cell Cycle and Its Control
      • Biochemical Studies with Oocytes, Eggs, and Early Embryos
      • Genetic Studies with S. pombe
      • Molecular Mechanisms for Regulating Mitotic Events
      • Genetic Studies with S. cerevisiae
      • Cell-Cycle Control in Mammalian Cells
      • Checkpoints in Cell-Cycle Regulation
  • 14. Gene Control in Development
    • 14.1. Cell-Type Specification and Mating-Type Conversion in Yeast
      • Combinations of DNA-Binding Proteins Regulate Cell-Type Specification in Yeast
      • Mating of α and a Cells Is Induced by Pheromone-Stimulated Gene Expression
      • Multiple Regulation of HO Transcription Controls Mating-Type Conversion
      • Silencer Elements Repress Expression at HML and HMR
      • SUMMARY
    • 14.2. Cell-Type Specification in Animals
      • Embryonic Somites Give Rise to Myoblasts, the Precursors of Skeletal Muscle Cells
      • Myogenic Genes Were First Identified in Studies with Cultured Fibroblasts
      • Myogenic Proteins Are Transcription Factors Containing a Common bHLH Domain
      • MEFs Function in Concert with MRFs to Confer Myogenic Specificity
      • Myogenic Stages at Which MRFs and MEFs Function in Vivo Have Been Identified
      • Multiple MRFs Exhibit Functional Diversity and Permit Flexibility in Regulating Development
      • Terminal Differentiation of Myoblasts Is under Positive and Negative Control
      • A Network of Cross-Regulatory Interactions Maintains the Myogenic Program
      • Neurogenesis Requires Regulatory Proteins Analogous to bHLH Myogenic Proteins
      • Progressive Restriction of Neural Potential Requires Inhibitory HLH Proteins and Local Cell-Cell Interactions
      • bHLH Regulatory Circuitry May Operate to Specify Other Cell Types
      • SUMMARY
    • 14.3. Anteroposterior Specification during Embryogenesis
      • Drosophila Has Two Life Forms
      • Patterning Information Is Generated during Oogenesis and Early Embryogenesis
      • Four Maternal Gene Systems Control Early Patterning in Fly Embryos
      • Morphogens Regulate Development as a Function of Their Concentration
      • Maternal bicoid Gene Specifies Anterior Region in Drosophila
      • Maternally Derived Inhibitors of Translation Contribute to Early Drosophila Patterning
      • Graded Expression of Several Gap Genes Further Subdivides the Fly Embryo into Unique Spatial Domains
      • Expression of Three Groups of Zygotic Genes Completes Early Patterning in Drosophila
      • Selector (Hox) Genes Occur in Clusters in the Genome
      • Combinations of Different Hox Proteins Contribute to Specifying Parasegment Identity in Drosophila
      • Specificity of Drosophila Hox-Protein Function Is Mediated by Exd Protein
      • Hox-Gene Expression Is Maintained by Autoregulation and Changes in Chromatin Structure
      • Mammalian Homologs of Drosophila ANT-C and BX-C Genes Occur in Four Hox Complexes
      • Mutations in Hox Genes Result in Homeotic Transformations in the Developing Mouse
      • SUMMARY
    • 14.4. Specification of Floral-Organ Identity in Arabidopsis
      • Flowers Contain Four Different Organs
      • Three Classes of Genes Control Floral-Organ Identity
      • Many Floral Organ–Identity Genes Encode MADS Family Transcription Factors
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
      • References
    • Testing Yourself on the concepts
    • MCAT/GRE-Style Questions
      • Key Concept
      • Key Experiment
      • Key Application
    • References
      • Cell-Type Specification and Mating-Type Conversion in Yeast
      • Cell-Type Specification in Animals
      • Anteroposterior Specification during Embryogenesis
      • Specification of Floral-Organ Identity in Arabidopsis
  • 15. Transport across Cell Membranes
    • 15.1. Diffusion of Small Molecules across Phospholipid Bilayers
    • 15.2. Overview of Membrane Transport Proteins
      • SUMMARY
    • 15.3. Uniporter-Catalyzed Transport
      • Three Main Features Distinguish Uniport Transport from Passive Diffusion
      • GLUT1 Transports Glucose into Most Mammalian Cells
      • SUMMARY
    • 15.4. Intracellular Ion Environment and Membrane Electric Potential
      • Ionic Gradients and an Electric Potential Are Maintained across the Plasma Membrane
      • The Membrane Potential in Animal Cells Depends Largely on Resting K+ Channels
      • Na+ Entry into Mammalian Cells Has a Negative ΔG
      • SUMMARY
    • 15.5. Active Transport by ATP-Powered Pumps
      • Plasma-Membrane Ca2+ ATPase Exports Ca2+ Ions from Cells
      • Muscle Ca2+ ATPase Pumps Ca2+ Ions from the Cytosol into the Sarcoplasmic Reticulum
      • Na+/K+ ATPase Maintains the Intracellular Na+ and K+ Concentrations in Animal Cells
      • V-Class H+ ATPases Pump Protons across Lysosomal and Vacuolar Membranes
      • The ABC Superfamily Transports a Wide Variety of Substrates
      • SUMMARY
    • 15.6. Cotransport by Symporters and Antiporters
      • Na+-Linked Symporters Import Amino Acids and Glucose into Many Animal Cells
      • Na+-Linked Antiporter Exports Ca2+ from Cardiac Muscle Cells
      • AE1 Protein, a Cl/HCO3 Antiporter, Is Crucial to CO2 Transport by Erythrocytes
      • Several Cotransporters Regulate Cytosolic pH
      • Numerous Transport Proteins Enable Plant Vacuoles to Accumulate Metabolites and Ions
      • SUMMARY
    • 15.7. Transport across Epithelia
      • The Intestinal Epithelium Is Highly Polarized
      • Transepithelial Movement of Glucose and Amino Acids Requires Multiple Transport Proteins
      • Parietal Cells Acidify the Stomach Contents While Maintaining a Neutral Cytosolic pH
      • Tight Junctions Seal Off Body Cavities and Restrict Diffusion of Membrane Components
      • Other Junctions Interconnect Epithelial Cells and Control Passage of Molecules between Them
      • SUMMARY
    • 15.8. Osmosis, Water Channels, and the Regulation of Cell Volume
      • Osmotic Pressure Causes Water to Move across Membranes
      • Different Cells Have Various Mechanisms for Controlling Cell Volume
      • Water Channels Are Necessary for Bulk Flow of Water across Cell Membranes
      • Simple Rehydration Therapy Depends on Osmotic Gradient Created by Absorption of Glucose and Na+
      • Changes in Intracellular Osmotic Pressure Cause Leaf Stomata to Open
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
      • References
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Concept
      • Key Experiment
      • Key Application
    • References
      • Uniporter-Catalyzed Transport of Specific Molecules
      • Ion Channels, Intracellular Ion Environment, and Membrane Electric Potential
      • Active Transport and ATP Hydrolysis
      • Cotransport Catalyzed by Symporters and Antiporters
      • Transport across Epithelia
      • Osmosis, Water Channels, and the Regulation of Cell Volume
  • 16. Cellular Energetics: Glycolysis, Aerobic Oxidation, and Photosynthesis
    • 16.1. Oxidation of Glucose and Fatty Acids to CO2
      • Cytosolic Enzymes Convert Glucose to Pyruvate
      • Substrate-Level Phosphorylation Generates ATP during Glycolysis
      • Anaerobic Metabolism of Each Glucose Molecule Yields Only Two ATP Molecules
      • Mitochondria Possess Two Structurally and Functionally Distinct Membranes
      • Mitochondrial Oxidation of Pyruvate Begins with the Formation of Acetyl CoA
      • Oxidation of the Acetyl Group of Acetyl CoA in the Citric Acid Cycle Yields CO2 and Reduced Coenzymes
      • Inner-Membrane Proteins Allow the Uptake of Electrons from Cytosolic NADH
      • Mitochondrial Oxidation of Fatty Acids Is Coupled to ATP Formation
      • Oxidation of Fatty Acids in Peroxisomes Generates No ATP
      • The Rate of Glucose Oxidation Is Adjusted to Meet the Cell’s Need for ATP
      • SUMMARY
    • 16.2. Electron Transport and Oxidative Phosphorylation
      • The Proton-Motive Force in Mitochondria Is Due Largely to a Voltage Gradient across the Inner Membrane
      • Electron Transport in Mitochondria Is Coupled to Proton Translocation
      • Electrons Flow from FADH2 and NADH to O2 via a Series of Multiprotein Complexes
      • CoQ and Cytochrome c Shuttle Electrons from One Electron Transport Complex to Another
      • Reduction Potentials of Electron Carriers Favor Electron Flow from NADH to O2
      • CoQ and Three Electron Transport Complexes Pump Protons out of the Mitochondrial Matrix
      • Experiments with Membrane Vesicles Support the Chemiosmotic Mechanism of ATP Formation
      • Bacterial Plasma-Membrane Proteins Catalyze Electron Transport and Coupled ATP Synthesis
      • ATP Synthase Comprises a Proton Channel (F0) and ATPase (F1)
      • The F0F1 Complex Harnesses the Proton-Motive Force to Power ATP Synthesis
      • Transporters in the Inner Mitochondrial Membrane Are Powered by the Proton-Motive Force
      • Rate of Mitochondrial Oxidation Normally Depends on ADP Levels
      • Brown-Fat Mitochondria Contain an Uncoupler of Oxidative Phosphorylation
      • SUMMARY
    • 16.3. Photosynthetic Stages and Light-Absorbing Pigments
      • Photosynthesis Occurs on Thylakoid Membranes
      • Three of the Four Stages in Photosynthesis Occur Only during Illumination
      • Each Photon of Light Has a Defined Amount of Energy
      • Chlorophyll a Is Present in Both Components of a Photosystem
      • Light Absorption by Reaction-Center Chlorophylls Causes a Charge Separation across the Thylakoid Membrane
      • Light-Harvesting Complexes Increase the Efficiency of Photosynthesis
      • SUMMARY
    • 16.4. Molecular Analysis of Photosystems
      • Photoelectron Transport in Purple Bacteria Produces a Charge Separation
      • Both Cyclic and Noncyclic Electron Transport Occur in Bacterial Photosynthesis
      • Chloroplasts Contain Two Functionally and Spatially Distinct Photosystems
      • An Oxygen-Evolving Complex in PSII Regenerates P680
      • Cyclic Electron Flow in PSI Generates ATP but No NADPH
      • PSI and PSII Are Functionally Coupled
      • Both Plant Photosystems Are Essential for Formation of NADPH and O2
      • SUMMARY
    • 16.5. CO2 Metabolism during Photosynthesis
      • CO2 Fixation Occurs in the Chloroplast Stroma
      • Synthesis of Sucrose Incorporating Fixed CO2 Is Completed in the Cytosol
      • Light Stimulates CO2 Fixation by Several Mechanisms
      • Photorespiration, Which Consumes O2 and Liberates CO2, Competes with Photosynthesis
      • The C4 Pathway for CO2 Fixation Is Used by Many Tropical Plants
      • Sucrose Is Transported from Leaves through the Phloem to All Plant Tissues
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
      • References
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Concept
      • Key Experiment
      • Key Concept
    • References
      • Oxidation of Glucose and Fatty Acids to CO2
      • Electron Transport and Oxidative Phosphorylation
      • Photosynthetic Stages and Light Absorbing Pigments
      • Molecular Analysis of Photosystems
      • CO2 Metabolism During Photosynthesis
  • 17. Protein Sorting: Organelle Biogenesis and Protein Secretion
    • 17.1. Synthesis and Targeting of Mitochondrial and Chloroplast Proteins
      • Most Mitochondrial Proteins Are Synthesized as Cytosolic Precursors Containing Uptake-Targeting Sequences
      • Cytosolic Chaperones Deliver Proteins to Channel-Linked Receptors in the Mitochondrial Membrane
      • Matrix Chaperones and Chaperonins Are Essential for the Import and Folding of Mitochondrial Proteins
      • Studies with Chimeric Proteins Confirm Major Features of Mitochondrial Import
      • The Uptake of Mitochondrial Proteins Requires Energy
      • Proteins Are Targeted to Submitochondrial Compartments by Multiple Signals and Several Pathways
      • The Synthesis of Mitochondrial Proteins Is Coordinated
      • Several Uptake-Targeting Sequences Direct Proteins Synthesized in the Cytosol to the Appropriate Chloroplast Compartment
      • SUMMARY
    • 17.2. Synthesis and Targeting of Peroxisomal Proteins
      • C- and N-Terminal Targeting Sequences Direct Entry of Folded Proteins into the Peroxisomal Matrix
      • Peroxisomal Protein Import Is Defective in Some Genetic Diseases
      • SUMMARY
    • 17.3. Overview of the Secretory Pathway
      • Secretory Proteins Move from the Rough ER Lumen through the Golgi Complex and Then to the Cell Surface
      • Analysis of Yeast Mutants Defined Major Steps in the Secretory Pathway
      • Anterograde Transport through the Golgi Occurs by Cisternal Progression
      • Plasma-Membrane Glycoproteins Mature via the Same Pathway as Continuously Secreted Proteins
      • SUMMARY
    • 17.4. Translocation of Secretory Proteins across the ER Membrane
      • A Signal Sequence on Nascent Secretory Proteins Targets Them to the ER and Is Then Cleaved Off
      • Two Proteins Initiate the Interaction of Signal Sequences with the ER Membrane
      • Polypeptides Move through the Translocon into the ER Lumen
      • GTP Hydrolysis Powers Protein Transport into the ER in Mammalian Cells
      • SUMMARY
    • 17.5. Insertion of Membrane Proteins into the ER Membrane
      • Most Nominal Cytosolic Transmembrane Proteins Have an N-Terminal Signal Sequence and an Internal Topogenic Sequence
      • A Single Internal Topogenic Sequence Directs Insertion of Some Single-Pass Transmembrane Proteins
      • Multipass Transmembrane Proteins Have Multiple Topogenic Sequences
      • After Insertion in the ER Membrane, Some Proteins Are Transferred to a GPI Anchor
      • SUMMARY
    • 17.6. Post-Translational Modifications and Quality Control in the Rough ER
      • Disulfide Bonds Are Formed and Rearranged in the ER Lumen
      • Correct Folding of Newly Made Proteins Is Facilitated by Several ER Proteins
      • Assembly of Subunits into Multimeric Proteins Occurs in the ER
      • Only Properly Folded Proteins Are Transported from the Rough ER to the Golgi Complex
      • Many Unassembled or Misfolded Proteins in the ER Are Transported to the Cytosol and Degraded
      • ER-Resident Proteins Often Are Retrieved from the Cis-Golgi
      • SUMMARY
    • 17.7. Protein Glycosylation in the ER and Golgi Complex
      • Different Structures Characterize N- and O-Linked Oligosaccharides
      • O-Linked Oligosaccharides Are Formed by the Sequential Transfer of Sugars from Nucleotide Precursors
      • ABO Blood Type Is Determined by Two Glycosyltransferases
      • A Common Preformed N-Linked Oligosaccharide Is Added to Many Proteins in the Rough ER
      • Modifications to N-Linked Oligosaccharides Are Completed in the Golgi Complex
      • Oligosaccharides May Promote Folding and Stability of Glycoproteins
      • Mannose 6-Phosphate Residues Target Proteins to Lysosomes
      • Lysosomal Storage Diseases Provided Clues to Sorting of Lysosomal Enzymes
      • SUMMARY
    • 17.8. Golgi and Post-Golgi Protein Sorting and Proteolytic Processing
      • Sequences in the Membrane-Spanning Domain Cause the Retention of Proteins in the Golgi
      • Different Vesicles Are Used for Continuous and Regulated Protein Secretion
      • Proproteins Undergo Proteolytic Processing Late in Maturation
      • Some Proteins Are Sorted from the Golgi Complex to the Apical or Basolateral Plasma Membrane
      • SUMMARY
    • 17.9. Receptor-Mediated Endocytosis and the Sorting of Internalized Proteins
      • The LDL Receptor Binds and Internalizes Cholesterol-Containing Particles
      • Cytosolic Sequences in Some Cell-Surface Receptors Target Them for Endocytosis
      • The Acidic pH of Late Endosomes Causes Most Receptors and Ligands to Dissociate
      • The Endocytic Pathway Delivers Transferrin-Bound Iron to Cells
      • Some Endocytosed Proteins Remain within the Cell
      • Transcytosis Moves Some Ligands across Cells
      • SUMMARY
    • 17.10. Molecular Mechanisms of Vesicular Traffic
      • At Least Three Types of Coated Vesicles Transport Proteins from Organelle to Organelle
      • Clathrin Vesicles Mediate Several Types of Intracellular Transport
      • COP I Vesicles Mediate Retrograde Transport within the Golgi and from the Golgi Back to the ER
      • COP II Vesicles Mediate Transport from the ER to the Golgi
      • Specific Fusion of Intracellular Vesicles Involves a Conserved Set of Fusion Proteins
      • Conformational Changes in Influenza HA Protein Trigger Membrane Fusion
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
      • References
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Concept
      • Key Experiment
      • Key Application
    • References
      • Synthesis and Targeting of Mitochondrial and Chloroplast Proteins
      • Synthesis and Targeting of Peroxisomal Proteins
      • Translocation of Secretory Proteins across the ER Membrane
      • Insertion of Membrane Proteins into the ER Membrane
      • Post-Translational Modifications and Quality Control in the Rough ER
      • Protein Glycosylation in the ER and Golgi Complex
      • Golgi and Post-Golgi Protein Sorting and Proteolytic Processing
      • Receptor-Mediated Endocytosis and the Sorting of Internalized Proteins
      • Molecular Mechanisms of Vesicular Traffic
  • 18. Cell Motility and Shape I: Microfilaments
    • 18.1. The Actin Cytoskeleton
      • Eukaryotic Cells Contain Abundant Amounts of Highly Conserved Actin
      • ATP Holds Together the Two Lobes of the Actin Monomer
      • G-Actin Assembles into Long, Helical F-Actin Polymers
      • F-Actin Has Structural and Functional Polarity
      • The Actin Cytoskeleton Is Organized into Bundles and Networks of Filaments
      • Cortical Actin Networks Are Connected to the Membrane
      • Actin Bundles Support Projecting Fingers of Membrane
      • SUMMARY
    • 18.2. The Dynamics of Actin Assembly
      • Actin Polymerization in Vitro Proceeds in Three Steps
      • Actin Filaments Grow Faster at One End Than at the Other
      • Toxins Disrupt the Actin Monomer-Polymer Equilibrium
      • Actin Polymerization Is Regulated by Proteins That Bind G-Actin
      • Some Proteins Control the Lengths of Actin Filaments by Severing Them
      • Actin Filaments Are Stabilized by Actin-Capping Proteins
      • Many Movements Are Driven by Actin Polymerization
      • SUMMARY
    • 18.3. Myosin: The Actin Motor Protein
      • All Myosins Have Head, Neck, and Tail Domains with Distinct Functions
      • Myosin Heads Walk along Actin Filaments
      • Myosin Heads Move in Discrete Steps, Each Coupled to Hydrolysis of One ATP
      • Myosin and Kinesin Share the Ras Fold with Certain Signaling Proteins
      • Conformational Changes in the Myosin Head Couple ATP Hydrolysis to Movement
      • SUMMARY
    • 18.4. Muscle: A Specialized Contractile Machine
      • Some Muscles Contract, Others Generate Tension
      • Skeletal Muscles Contain a Regular Array of Actin and Myosin
      • Smooth Muscles Contain Loosely Organized Thick and Thin Filaments
      • Thick and Thin Filaments Slide Past One Another during Contraction
      • Titin and Nebulin Filaments Organize the Sarcomere
      • A Rise in Cytosolic Ca2+ Triggers Muscle Contraction
      • Actin-Binding Proteins Regulate Contraction in Both Skeletal and Smooth Muscle
      • Myosin-Dependent Mechanisms Also Control Contraction in Some Muscles
      • SUMMARY
    • 18.5. Actin and Myosin in Nonmuscle Cells
      • Actin and Myosin II Are Arranged in Contractile Bundles That Function in Cell Adhesion
      • Myosin II Stiffens Cortical Membranes
      • Actin and Myosin II Have Essential Roles in Cytokinesis
      • Membrane-Bound Myosins Power Movement of Some Vesicles
      • SUMMARY
    • 18.6. Cell Locomotion
      • Controlled Polymerization and Rearrangements of Actin Filaments Occur during Keratinocyte Movement
      • Ameboid Movement Involves Reversible Gel-Sol Transitions of Actin Networks
      • Myosin I and Myosin II Have Important Roles in Cell Migration
      • Migration of Cells Is Coordinated by Various Second Messengers and Signal-Transduction Pathways
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
      • References
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Concept
      • Key Experiment
      • Key Concept
    • References
      • General References
      • Web Sites
      • Actin Cytoskeleton
      • Dynamics of Actin Assembly
      • Myosin: The Actin Motor Protein
      • Muscle: A Specialized Contractile Machine
      • Actin and Myosin in Nonmuscle Cells
      • Cell Locomotion
  • 19. Cell Motility and Shape II: Microtubules and Intermediate Filaments
    • 19.1. Microtubule Structures
      • Heterodimeric Tubulin Subunits Compose the Wall of a Microtubule
      • Microtubules Form a Diverse Array of Both Permanent and Transient Structures
      • Microtubules Assemble from Organizing Centers
      • Most Microtubules Have a Constant Orientation Relative to MTOCs
      • The γ-Tubulin Ring Complex Nucleates Polymerization of Tubulin Subunits
      • SUMMARY
    • 19.2. Microtubule Dynamics and Associated Proteins
      • Microtubule Assembly and Disassembly Occur Preferentially at the (+) End
      • Dynamic Instability Is an Intrinsic Property of Microtubules
      • Colchicine and Other Drugs Disrupt Microtubule Dynamics
      • Assembly MAPs Cross-Link Microtubules to One Another and Other Structures
      • Bound MAPs Alter Microtubule Dynamics
      • SUMMARY
    • 19.3. Kinesin, Dynein, and Intracellular Transport
      • Fast Axonal Transport Occurs along Microtubules
      • Microtubules Provide Tracks for the Movement of Pigment Granules
      • Intracellular Membrane Vesicles Travel along Microtubules
      • Kinesin Is a (+) End–Directed Microtubule Motor Protein
      • Each Member of the Kinesin Family Transports a Specific Cargo
      • Dynein Is a (−) End – Directed Motor Protein
      • Dynein-Associated MBPs Tether Cargo to Microtubules
      • Multiple Motor Proteins Are Associated with Membrane Vesicles
      • SUMMARY
    • 19.4. Cilia and Flagella: Structure and Movement
      • All Eukaryotic Cilia and Flagella Contain Bundles of Doublet Microtubules
      • Ciliary and Flagellar Beating Are Produced by Controlled Sliding of Outer Doublet Microtubules
      • Dynein Arms Generate the Sliding Forces in Axonemes
      • Axonemal Dyneins Are Multiheaded Motor Proteins
      • Conversion of Microtubule Sliding into Axonemal Bending Depends on Inner-Arm Dyneins
      • Proteins Associated with Radial Spokes May Control Flagellar Beat
      • Axonemal Microtubules Are Dynamic and Stable
      • SUMMARY
    • 19.5. Microtubule Dynamics and Motor Proteins during Mitosis
      • The Mitotic Apparatus Is a Microtubule Machine for Separating Chromosomes
      • The Kinetochore Is a Specialized Attachment Site at the Chromosome Centromere
      • Centrosome Duplication Precedes and Is Required for Mitosis
      • Dynamic Instability of Microtubules Increases during Mitosis
      • Organization of the Spindle Poles Orients the Assembly of the Mitotic Apparatus
      • Formation of Poles and Capture of Chromosomes Are Key Events in Spindle Assembly
      • Kinetochores Generate the Force for Poleward Chromosome Movement
      • During Anaphase Chromosomes Separate and the Spindle Elongates
      • Astral Microtubules Determine Where Cytokinesis Takes Place
      • Plant Cells Reorganize Their Microtubules and Build a New Cell Wall during Mitosis
      • SUMMARY
    • 19.6. Intermediate Filaments
      • Functions and Structure of Intermediate Filaments Distinguish Them from Other Cytoskeletal Fibers
      • IF Proteins Are Classified into Six Types
      • Intermediate Filaments Can Identify the Cellular Origin of Certain Tumors
      • All IF Proteins Have a Conserved Core Domain and Are Organized Similarly into Filaments
      • Intermediate Filaments Are Dynamic Polymers in the Cell
      • Various Proteins Cross-Link Intermediate Filaments and Connect Them to Other Cell Structures
      • IF Networks Support Cellular Membranes
      • Intermediate Filaments Are Anchored in Cell Junctions
      • Desmin and Associated Proteins Stabilize Sarcomeres in Muscle
      • Disruption of Keratin Networks Causes Blistering
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
      • References
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Concept
      • Key Experiment
      • Key Application
    • References
      • Microtubule Structures
      • Microtubule Dynamics and Associated Proteins
      • Kinesin, Dynein, and Intracellular Transport
      • Cilia and Flagella: Structure and Movement
      • Microtubule Dynamics and Motor Proteins during Mitosis
      • Intermediate Filaments
  • 20. Cell-to-Cell Signaling: Hormones and Receptors
    • 20.1. Overview of Extracellular Signaling
      • Signaling Molecules Operate over Various Distances in Animals
      • Receptor Proteins Exhibit Ligand-Binding and Effector Specificity
      • Hormones Can Be Classified Based on Their Solubility and Receptor Location
      • Cell-Surface Receptors Belong to Four Major Classes
      • Effects of Many Hormones Are Mediated by Second Messengers
      • Other Conserved Proteins Function in Signal Transduction
      • Common Signaling Pathways Are Initiated by Different Receptors in a Class
      • The Synthesis, Release, and Degradation of Hormones Are Regulated
      • SUMMARY
    • 20.2. Identification and Purification of Cell-Surface Receptors
      • Hormone Receptors Are Detected by Binding Assays
      • KD Values for Cell-Surface Hormone Receptors Approximate the Concentrations of Circulating Hormones
      • Affinity Techniques Permit Purification of Receptor Proteins
      • Many Receptors Can Be Cloned without Prior Purification
      • SUMMARY
    • 20.3. G Protein –Coupled Receptors and Their Effectors
      • Binding of Epinephrine to Adrenergic Receptors Induces Tissue-Specific Responses
      • Stimulation of β-Adrenergic Receptors Leads to a Rise in cAMP
      • Critical Features of Catecholamines and Their Receptors Have Been Identified
      • Trimeric Gs Protein Links β-Adrenergic Receptors and Adenylyl Cyclase
      • Some Bacterial Toxins Irreversibly Modify G Proteins
      • Adenylyl Cyclase Is Stimulated and Inhibited by Different Receptor-Ligand Complexes
      • GTP-Induced Changes in G Favor Its Dissociation from Gβγ and Association with Adenylyl Cyclase
      • G and G Interact with Different Regions of Adenylyl Cyclase
      • Degradation of cAMP Also Is Regulated
      • SUMMARY
    • 20.4. Receptor Tyrosine Kinases and Ras
      • Ligand Binding Leads to Autophosphorylation of RTKs
      • Ras and Gα Subunits Belong to the GTPase Superfamily of Intracellular Switch Proteins
      • An Adapter Protein and GEF Link Most Activated RTKs to Ras
      • SH2 Domain in GRB2 Adapter Protein Binds to a Specific Phosphotyrosine in an Activated RTK
      • Sos, a Guanine Nucleotide – Exchange Factor, Binds to the SH3 Domains in GRB2
      • SUMMARY
    • 20.5. MAP Kinase Pathways
      • Signals Pass from Activated Ras to a Cascade of Protein Kinases
      • Ksr May Function as a Scaffold for the MAP Kinase Cascade Linked to Ras
      • Phosphorylation of a Tyrosine and a Threonine Activates MAP Kinase
      • Various Types of Receptors Transmit Signals to MAP Kinase
      • Multiple MAP Kinase Pathways Are Found in Eukaryotic Cells
      • Specificity of MAP Kinase Pathways Depends on Several Mechanisms
      • SUMMARY
    • 20.6. Second Messengers
      • cAMP and Other Second Messengers Activate Specific Protein Kinases
      • cAPKs Activated by Epinephrine Stimulation Regulate Glycogen Metabolism
      • Kinase Cascades Permit Multienzyme Regulation and Amplify Hormone Signals
      • Cellular Responses to cAMP Vary among Different Cell Types
      • Anchoring Proteins Localize Effects of cAMP to Specific Subcellular Regions
      • Modification of a Common Phospholipid Precursor Generates Several Second Messengers
      • Hormone-Induced Release of Ca2+ from the ER Is Mediated by IP3
      • Opening of Ryanodine Receptors Releases Ca2+ Stores in Muscle and Nerve Cells
      • Ca2+-Calmodulin Complex Mediates Many Cellular Responses
      • DAG Activates Protein Kinase C, Which Regulates Many Other Proteins
      • Synthesis of cGMP Is Induced by Both Peptide Hormones and Nitric Oxide
      • SUMMARY
    • 20.7. Interaction and Regulation of Signaling Pathways
      • The Same RTK Can Be Linked to Different Signaling Pathways
      • Multiple G Proteins Transduce Signals to Different Effector Proteins
      • Gβγ Acts Directly on Some Effectors in Mammalian Cells
      • Glycogenolysis Is Promoted by Multiple Second Messengers
      • Insulin Stimulation Activates MAP Kinase and Protein Kinase B
      • Insulin and Glucagon Work Together to Maintain a Stable Blood Glucose Level
      • Receptors for Many Peptide Hormones Are Down-Regulated by Endocytosis
      • Phosphorylation of Cell-Surface Receptors Modulates Their Activity
      • Arrestins Have Two Roles in Regulating G Protein – Coupled Receptors
      • SUMMARY
    • 20.8. From Plasma Membrane to Nucleus
      • CREB Links cAMP Signals to Transcription
      • MAP Kinase Regulates the Activity of Many Transcription Factors
      • Phosphorylation-Dependent Protein Degradation Regulates NF-κB
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
      • References
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Application
      • Key Concept
      • Key Experiment
    • References
      • Overview of Extracellular Signaling
      • Identification and Purification of Cell-Surface Receptors
      • G Protein–Coupled Receptors and Their Effectors
      • Receptor Tyrosine Kinases and Ras
      • MAP Kinase Pathways
      • Second Messengers
      • Interaction and Regulation of Signaling Pathway
      • From Plasma Membrane to Nucleus
  • 21. Nerve Cells
    • 21.1. Overview of Neuron Structure and Function
      • Specialized Regions of Neurons Carry Out Different Functions
      • Synapses Are Specialized Sites Where Neurons Communicate with Other Cells
      • Neurons Are Organized into Circuits
      • SUMMARY
    • 21.2. The Action Potential and Conduction of Electric Impulses
      • The Resting Potential, Generated Mainly by Open “Resting” K+ Channels, Is Near EK
      • Opening and Closing of Ion Channels Cause Predictable Changes in the Membrane Potential
      • Membrane Depolarizations Spread Passively Only Short Distances
      • Voltage-Gated Cation Channels Generate Action Potentials
      • Action Potentials Are Propagated Unidirectionally without Diminution
      • Movements of Only a Few Na+ and K+ Ions Generate the Action Potential
      • Myelination Increases the Velocity of Impulse Conduction
      • SUMMARY
    • 21.3. Molecular Properties of Voltage-Gated Ion Channels
      • Patch Clamps Permit Measurement of Ion Movements through Single Channels
      • Voltage-Gated K+ Channels Have Four Subunits Each Containing Six Transmembrane α Helices
      • P Segments Form the Ion-Selectivity Filter
      • The S4 Transmembrane α Helix Acts as a Voltage Sensor
      • Movement of One N-Terminal Segment Inactivates Shaker K+ Channels
      • All Pore-Forming Ion Channels Are Similar in Structure to the Shaker K+ Channel
      • Voltage-Gated Channel Proteins Probably Evolved from a Common Ancestral Gene
      • SUMMARY
    • 21.4. Neurotransmitters, Synapses, and Impulse Transmission
      • Many Small Molecules Transmit Impulses at Chemical Synapses
      • Influx of Ca2+ Triggers Release of Neurotransmitters
      • Synaptic Vesicles Can Be Filled, Exocytosed, and Recycled within a Minute
      • Multiple Proteins Participate in Docking and Fusion of Synaptic Vesicles
      • Chemical Synapses Can Be Excitatory or Inhibitory
      • Two Classes of Neurotransmitter Receptors Operate at Vastly Different Speeds
      • Acetylcholine and Other Transmitters Can Activate Multiple Receptors
      • Transmitter-Mediated Signaling Is Terminated by Several Mechanisms
      • Impulses Transmitted across Chemical Synapses Can be Amplified and Computed
      • Impulse Transmission across Electric Synapses Is Nearly Instantaneous
      • SUMMARY
    • 21.5. Neurotransmitter Receptors
      • Opening of Acetylcholine-Gated Cation Channels Leads to Muscle Contraction
      • All Five Subunits in the Nicotinic Acetylcholine Receptor Contribute to the Ion Channel
      • Two Types of Glutamate-Gated Cation Channels May Function in a Type of “Cellular Memory”
      • GABA- and Glycine-Gated Cl Channels Are Found at Many Inhibitory Synapses
      • Cardiac Muscarinic Acetylcholine Receptors Activate a G Protein That Opens K+ Channels
      • Catecholamine Receptors Induce Changes in Second-Messenger Levels That Affect Ion-Channel Activity
      • A Serotonin Receptor Indirectly Modulates K+ Channel Function by Activating Adenylate Cyclase
      • Some Neuropeptides Function as Both Transmitters and Hormones
      • SUMMARY
    • 21.6. Sensory Transduction
      • Mechanoreceptors and Some Other Sensory Receptors Are Gated Cation Channels
      • Visual Signals Are Processed at Multiple Levels
      • The Light-Triggered Closing of Na+ Channels Hyperpolarizes Rod Cells
      • Absorption of a Photon Triggers Isomerization of Retinal and Activation of Opsin
      • Cyclic GMP Is a Key Transducing Molecule in Rod Cells
      • Rod Cells Adapt to Varying Levels of Ambient Light
      • Color Vision Utilizes Three Opsin Pigments
      • A Thousand Different G Protein – Coupled Receptors Detect Odors
      • SUMMARY
    • 21.7. Learning and Memory
      • Repeated Conditioned Stimuli Cause Decrease in Aplysia Withdrawal Response
      • Facilitator Neurons Mediate Sensitization of Aplysia Withdrawal Reflex
      • Coincidence Detectors Participate in Classical Conditioning and Sensitization
      • Long-Term Memory Requires Protein Synthesis
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
      • References
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Concept
      • Key Experiment
      • Key Application
    • References
      • Overview of Neuron Structure and Function
      • The Action Potential and Conduction of Electric Impulses
      • Molecular Properties of Voltage-Gated Ion Channels
      • Neurotransmitters, Synapses, and Impulse Transmission
      • Neurotransmitter Receptors
      • Sensory Transduction
      • Learning and Memory
  • 22. Integrating Cells into Tissues
    • 22.1. Cell-Cell Adhesion and Communication
      • Cadherins Mediate Ca2+-Dependent Homophilic Cell-Cell Adhesion
      • N-CAMs Mediate Ca2+-Independent Homophilic Cell-Cell Adhesion
      • Selectins and Other CAMs Participate in Leukocyte Extravasation
      • Cadherin-Containing Junctions Connect Cells to One Another
      • Gap Junctions Allow Small Molecules to Pass between Adjacent Cells
      • Connexin, a Transmembrane Protein, Forms Cylindrical Channels in Gap Junctions
      • SUMMARY
    • 22.2. Cell-Matrix Adhesion
      • Integrins Mediate Weak Cell-Matrix and Cell-Cell Interactions
      • Cell-Matrix Adhesion Is Modulated by Changes in the Activity and Number of Integrins
      • De-adhesion Factors Promote Cell Migration and Can Remodel the Cell Surface
      • Integrin-Containing Junctions Connect Cells to the Substratum
      • SUMMARY
    • 22.3. Collagen: The Fibrous Proteins of the Matrix
      • The Basic Structural Unit of Collagen Is a Triple Helix
      • Collagen Fibrils Form by Lateral Interactions of Triple Helices
      • Assembly of Collagen Fibers Begins in the ER and Is Completed outside the Cell
      • Mutations in Collagen Reveal Aspects of Its Structure and Biosynthesis
      • Collagens Form Diverse Structures
      • SUMMARY
    • 22.4. Noncollagen Components of the Extracellular Matrix
      • Laminin and Type IV Collagen Form the Two-Dimensional Reticulum of the Basal Lamina
      • Fibronectins Bind Many Cells to Fibrous Collagens and Other Matrix Components
      • Proteoglycans Consist of Multiple Glycosaminoglycans Linked to a Core Protein
      • Many Growth Factors Are Sequestered and Presented to Cells by Proteoglycans
      • Hyaluronan Resists Compression and Facilitates Cell Migration
      • SUMMARY
    • 22.5. The Dynamic Plant Cell Wall
      • The Cell Wall Is a Laminate of Cellulose Fibrils in a Pectin and Hemicellulose Matrix
      • Cell Walls Contain Lignin and an Extended Hydroxyproline-Rich Glycoprotein
      • A Plant Hormone, Auxin, Signals Cell Expansion
      • Cellulose Fibrils Are Synthesized and Oriented at the Plant Cortex
      • Plasmodesmata Directly Connect the Cytosol of Adjacent Cells in Higher Plants
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Concept
      • Key Application
      • Key Experiment
    • References
      • General References
      • Cell-Cell Adhesion and Communication
      • Cell-Matrix Adhesion
      • Collagen
      • Noncollagen Components of the Extracellular Matrix
      • The Dynamic Plant Cell Wall
  • 23. Cell Interactions in Development
    • 23.1. Dorsoventral Patterning by TGFβ-Superfamily Proteins
      • TGFβ Proteins Bind to Receptors That Have Serine/Threonine Kinase Activity
      • Activated TGFβ Receptors Phosphorylate Smad Transcription Factors
      • Dpp Protein, a TGFβ Homolog, Controls Dorsoventral Patterning in Drosophila Embryos
      • Sequential Inductive Events Regulate Early Xenopus Development
      • Inductive Effect of TGFβ Homologs Is Regulated Post-Translationally
      • A Highly Conserved Pathway Determines Dorsoventral Patterning in Invertebrates and Vertebrates
      • SUMMARY
    • 23.2. Tissue Patterning by Hedgehog and Wingless
      • Modification of Secreted Hedgehog Precursor Yields a Cell-Tethered Inductive Signal
      • Binding of Hedgehog to the Patch Receptor Relieves Inhibition of Smo
      • Hedgehog Organizes Pattern in the Chick Limb and Drosophila Wing
      • Hedgehog Induces Wingless, Which Triggers a Highly Conserved Signaling Pathway
      • SUMMARY
    • 23.3. Molecular Mechanisms of Responses to Morphogens
      • Hedgehog Gradient Elicits Different Cell Fates in the Vertebrate Neural Tube
      • Cells Can Detect the Number of Ligand-Occupied Receptors
      • Target Genes That Respond Differentially to Morphogens Have Different Control Regions
      • SUMMARY
    • 23.4. Reciprocal and Lateral Inductive Interactions
      • Reciprocal Epithelial-Mesenchymal Interactions Regulate Kidney Development
      • Activation of the Ret Receptor Promotes Growth and Branching of the Ureteric Bud
      • The Basal Lamina Is Essential for Differentiation of Many Epithelial Cells
      • Cell-Surface Ephrin Ligands and Receptors Mediate Reciprocal Induction during Angiogenesis
      • The Conserved Notch Pathway Mediates Lateral Interactions
      • Interactions between Two Equivalent Cells Give Rise to AC and VU cells in C. elegans
      • Neuronal Development in Drosophila and Vertebrates Depends on Lateral Interactions
      • SUMMARY
    • 23.5. Overview of Neuronal Outgrowth
      • Individual Neurons Can Be Identified Reproducibly and Studied
      • Growth Cones Guide the Migration and Elongation of Developing Axons
      • Different Neurons Navigate along Different Outgrowth Pathways
      • Various Extracellular-Matrix Components Support Neuronal Outgrowth
      • Growth Cones Navigate along Specific Axon Tracts
      • Soluble Graded Signals Can Attract and Repel Growth Cones
      • SUMMARY
    • 23.6. Directional Control of Neuronal Outgrowth
      • Three Genes Control Dorsoventral Outgrowth of Neurons in C. elegans
      • Vertebrate Homologs of C. elegans UNC-6 Both Attract and Repel Growth Cones
      • UNC-40 Mediates Chemoattraction in Response to Netrin in Vertebrates
      • UNC-5 and UNC-40 Together Mediate Chemorepulsion in Response to Netrin
      • Prior Experience Modulates Growth-Cone Response to Netrin
      • Other Signaling Systems Can Both Attract and Repel Growth Cones
      • SUMMARY
    • 23.7. Formation of Topographic Maps and Synapses
      • Visual Stimuli Are Mapped onto the Tectum
      • Temporal Retinal Axons Are Repelled by Posterior Tectal Membranes
      • Ephrin A Ligands Are Expressed as a Gradient along the Anteroposterior Tectal Axis
      • The EphA3 Receptor Is Expressed in a Nasal-Temporal Gradient in the Retina
      • Motor Neurons Induce Assembly of the Neuromuscular Junction
      • SUMMARY
    • 23.8. Cell Death and Its Regulation
      • Programmed Cell Death Occurs through Apoptosis
      • Neutrophins Promote Survival of Neurons
      • Three Classes of Proteins Function in the Apoptotic Pathway
      • Pro-Apoptotic Regulators Promote Caspase Activation
      • Some Trophic Factors Prevent Apoptosis by Inducing Inactivation of a Pro-Apoptotic Regulator
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
      • References
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Concept
      • Key Application
      • Key Experiment
    • References
      • Dorsoventral Patterning by TGFβ-Superfamily Proteins
      • Tissue Patterning by Hedgehog and Wingless
      • Molecular Mechanisms of Responses to Morphogens
      • Reciprocal and Lateral Inductive Interactions
      • Overview of Neuronal Outgrowth
      • Directional Control of Neuronal Outgrowth
      • Formation of Topographic Maps and Synapses
      • Cell Death and Its Regulation
  • 24. Cancer
    • 24.1. Tumor Cells and the Onset of Cancer
      • Metastatic Tumor Cells Are Invasive and Can Spread
      • Alterations in Cell-to-Cell Interactions Are Associated with Malignancy
      • Tumor Growth Requires Formation of New Blood Vessels
      • DNA from Tumor Cells Can Transform Normal Cultured Cells
      • Development of a Cancer Requires Several Mutations
      • Cancers Originate in Proliferating Cells
      • SUMMARY
    • 24.2. Proto-Oncogenes and Tumor-Suppressor Genes
      • Gain-of-Function Mutations Convert Proto-Oncogenes into Oncogenes
      • Oncogenes Were First Identified in Cancer-Causing Retroviruses
      • Slow-Acting Carcinogenic Retroviruses Can Activate Cellular Proto-Oncogenes
      • Many DNA Viruses Also Contain Oncogenes
      • Loss-of-Function Mutations in Tumor-Suppressor Genes Are Oncogenic
      • The First Tumor-Suppressor Gene Was Identified in Patients with Inherited Retinoblastoma
      • Loss of Heterozygosity of Tumor-Suppressor Genes Occurs by Mitotic Recombination or Chromosome Mis-segregation
      • SUMMARY
    • 24.3. Oncogenic Mutations Affecting Cell Proliferation
      • Misexpressed Growth-Factor Genes Can Autostimulate Cell Proliferation
      • Virus-Encoded Activators of Growth-Factor Receptors Act as Oncoproteins
      • Activating Mutations or Overexpression of Growth-Factor Receptors Can Transform Cells
      • Constitutively Active Signal-Transduction Proteins Are Encoded by Many Oncogenes
      • Deletion of the PTEN Phosphatase Is a Frequent Occurrence in Human Tumors
      • Inappropriate Expression of Nuclear Transcription Factors Can Induce Transformation
      • SUMMARY
    • 24.4. Mutations Causing Loss of Cell-Cycle Control
      • Passage from G1 to S Phase Is Controlled by Proto-Oncogenes and Tumor-Suppressor Genes
      • Loss of TGFβ Signaling Contributes to Abnormal Cell Proliferation and Malignancy
      • SUMMARY
    • 24.5. Mutations Affecting Genome Stability
      • Mutations in p53 Abolish G1 Checkpoint Control
      • Proteins Encoded by DNA Tumor Viruses Can Inhibit p53 Activity
      • Some Human Carcinogens Cause Inactivating Mutations in the p53 Gene
      • Defects in DNA-Repair Systems Perpetuate Mutations and Are Associated with Certain Cancers
      • Chromosomal Abnormalities Are Common in Human Tumors
      • Telomerase Expression May Contribute to Immortalization of Cancer Cells
      • SUMMARY
    • PERSPECTIVES for the Future
    • PERSPECTIVES in the Literature
      • References
    • Testing Yourself on the Concepts
    • MCAT/GRE-Style Questions
      • Key Concept
      • Key Experiment
      • Key Concept
    • References
      • Tumor Cells and the Onset of Cancer
      • Oncogenic Mutations Affecting Cell Proliferation
      • Mutations Causing Loss of Cell-Cycle Control
      • Mutations Affecting Genome Stability
  • Glossary

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Copyright © 2000, W. H. Freeman and Company.
Bookshelf ID: NBK21475

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