Book , Print in English

Molecular cell biology

Harvey Lodish [and others].
  • New York : W.H. Freeman and Company, 2003.
  • 5th ed.
  • xxxiii, 973, [79] pages : illustrations (chiefly color) ; 28 cm
Subjects
Medical Subjects
Local Subjects
Summary
  • Emphasizing the experimental basis of current understandings in molecular biology, the text introduces experimental methodologies and concepts. Thirteen chapters cover such topics as biomembranes and cell architecture, cell integration in tissues, cell transport mechanisms, cellular energetics, molecular genetic techniques, transcriptional control of gene expression, and signaling at the cell surface.
Contents
  • note: 1 Life Begins with Cells
  • 1.1 The Diversity and Commonality of Cells
  • All Cells Are Prokaryotic or Eukaryotic
  • Unicellular Organisms Help and Hurt Us
  • Even Single Cells Can Have Sex
  • Viruses Are the Ultimate Parasites
  • We Develop from a Single Cell
  • Stem Cells, Cloning, and Related Techniques Offer Exciting Possibilities but Raise Some Concerns
  • 1.2 The Molecules of a Cell
  • Small Molecules Carry Energy, Transmit Signals, and Are Linked into Macromolecules
  • Proteins Give Cells Structure and Perform Most Cellular Tasks
  • Nucleic Acids Carry Coded Information for Making Proteins at the Right Time and Place
  • Genome Is Packaged into Chromosomes and Replicated During Cell Division
  • Mutations May Be Good, Bad, or Indifferent
  • 1.3 The Work of Cells
  • Cells Build and Degrade Numerous Molecules and Structures
  • Animal Cells Produce Their Own External Environment and Glues
  • Cells Change Shape and Move
  • Cells Sense and Send Information
  • Cells Regulate Their Gene Expression to Meet Changing Needs
  • Cells Grow and Divide
  • Cells Die from Aggravated Assault or an Internal Program
  • 1.4 Investigating Cells and Their Parts
  • Cell Biology Reveals the Size, Shape, and Location and Cell Components
  • Biochemistry Reveals the Molecular Structure and Chemistry of Purified Cell Constituents
  • Genetics Reveals the Consequences of Damaged Genes
  • Genomics Reveals Differences in the Structure and Expression of Entire Genomes
  • Developmental Biology Reveals Changes in the Properties of Cells as They Specialize
  • Choosing the Right Experimental Organism for the Job
  • 1.5 A Genome Perspective on Evolution
  • Metabolic Proteins, the Genetic Code, and Organelle Structures Are Nearly Universal
  • Many Genes Controlling Development Are Remarkably Similar in Humans and Other Animals
  • Darwin's Ideas About the Evolution of Whole Animals Are Relevant to Genes
  • Human Medicine Is Informed by Research on Other Organisms
  • 2 Chemical Foundations
  • 2.1 Atomic Bonds and Molecular Interactions
  • Each Atom Has a Defined Number and Geometry of Covalent Bonds
  • Electrons Are Shared Unequally in Polar Covalent Bonds
  • Covalent Bonds Are Much Stronger and More Stable Than Noncovalent Interactions
  • Ionic Interactions Are Attractions Between Oppositely Charged Ions
  • Hydrogen Bonds Determine Water Solubility of Uncharged Molecules
  • Van der Waals Interactions Are Caused by Transient Dipoles
  • Hydrophobic Effect Causes Nonpolar Molecules to Adhere to One Another
  • Molecular Complementarity Permits Tight, Highly Specific Binding of Biomolecules
  • 2.2 Chemical Building Blocks of Cells
  • Amino Acids Differing Only in Their Side
  • Chains Compose Proteins
  • Five Different Nucleotides Are Used to Build Nucleic Acids
  • Monosaccharides Joined by Glycosidic Bonds Form Linear and Branched Polysaccharides
  • Fatty Acids Are Precursors for Many Cellular Lipids
  • Phospholipids Associate Noncovalently to Form the Basic Bilayer Structure of Biomembranes
  • 2.3 Chemical Equilibrium
  • Equilibrium Constant Reflect the Extent of a Chemical Reaction
  • Chemical Reactions in Cells Are at Steady State
  • Dissociation Constants for Binding Reactions Reflect the Affinity of Interacting Molecules
  • Biological Fluids Have Characteristic pH Values
  • Hydrogen Ions Are Released by Acids and Taken Up by Bases
  • Buffers Maintain the pH of Intracellular and Extracellular Fluids
  • 2.4 Biochemical Energetics
  • Several Forms of Energy Are Important in Biological Systems
  • Cells Can Transform One Type of Energy into Another
  • Change in Free Energy Determines the Direction of a Chemical Reaction
  • ΔG°' of a Reaction Can Be Calculated from Its Keq
  • Unfavorable Chemical Reaction Can Proceed If It Is Coupled with an Energetically Favorable Reaction
  • Hydrolysis of ATP Releases Substantial Free Energy and Drives Many Cellular Processes
  • ATP Is Generated During Photosynthesis and Respiration
  • NAD+ and FAD Couple Many Biological Oxidation and Reduction Reactions
  • 3 Protein Structure and Function
  • 3.1 Hierarchical Structure of Proteins
  • Primary Structure of a Protein Is Its Linear Arrangement of Amino Acids
  • Secondary Structures Are the Core Elements of Protein Architecture
  • Overall Folding of a Polypeptide Chain Yields Its Tertiary Structure
  • Motifs Are Combinations of Secondary Structures
  • Structural and Functional Domains Are Modules of Tertiary Structure
  • Proteins Associate into Multimeric Structures and Macromolecular Assemblies
  • Members of Protein Families Have a Common Evolutionary Ancestor
  • 3.2 Folding, Modification, and Degradation of Proteins
  • Information for Protein Folding Is Encoded in the Sequence
  • Folding of Proteins in Vivo Is Promoted by Chaperones
  • Many Proteins Undergo Chemical Modification of Amino Acid Residues
  • Peptide Segments of Some Proteins Are Removed After Synthesis
  • Ubiquitin Marks Cytosolic Proteins for Degradation in Proteasomes
  • Digestive Proteases Degrade Dietary Proteins
  • Alternatively Folded Proteins Are Implicated in Slowly Developing Diseases
  • 3.3 Enzymes and the Chemical Work of Cells
  • Specificity and Affinity of Protein-Ligand Binding Depend on Molecular Complementarity
  • Enzymes Are Highly Efficient and Specific Catalysts
  • Enzyme's Active Site Binds Substrates and Carries Out Catalysis
  • Vmax and Km Characterize an Enzymatic Reaction
  • Enzymes in a Common Pathway Are Often Physically Associated with One Another
  • 3.4 Molecular Motors and the Mechanical Work of Cells
  • Molecular Motors Convert Energy into Motion
  • All Myosins Have Head, Neck, and Tail Domains with Distinct Functions
  • Conformational Changes in the Myosin Head Couple ATP Hydrolysis to Movement
  • 3.5 Common Mechanisms for Regulating Protein Function
  • Cooperative Binding Increases a Protein's Response to Small Changes in Ligand Concentration
  • Ligand Binding Can Induce Allosteric Release of Catalytic Subunits or Transition to a State with Different Activity
  • Calcium and GTP Are Widely Used to Modulate Protein Activity
  • Cyclic Protein Phosphorylation and Dephosphorylation Regulate Many Cellular Functions
  • Proteolytic Cleavage Irreversibly Activates or Inactivates Some Proteins
  • Higher-Order Regulation Includes Control of Protein Location and Concentration
  • 3.6 Purifying, Detecting, and Characterizing Proteins
  • Centrifugation Can Separate Particles and Molecules That Differ in Mass or Density
  • Electrophoresis Separates Molecules on the Basis of 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
  • Mass Spectrometry Measures the Mass of Proteins and Peptides
  • Protein Primary Structure Can Be Determined by Chemical Methods and from Gene Sequences
  • Peptides with a Defined Sequence Can Be Synthesized Chemically
  • Protein Conformation Is Determined by Sophisticated Physical Methods
  • 4 Basic Molecular Genetic Mechanisms
  • 4.1 Structure of Nucleic Acids
  • Nucleic Acid Strand Is a Linear Polymer with End-to-End Directionality
  • Native DNA Is a Double Helix of Complementary Antiparallel Strands
  • DNA Can Undergo Reversible Strand Separation
  • Many DNA Molecules Are Circular
  • Different Types of RNA Exhibit Various Confirmations Related to Their Functions
  • 4.2 Transcription of Protein-Coding Genes and Formation of Functional mRNA
  • Template DNA Strand Is Transcribed into a Complementary RNA Chain by RNA Polymerase
  • Organization of Genes Differs in Prokaryotic and Eukaryotic DNA
  • Eukaryotic Precursor mRNAs Are Processed to Form Functional mRNAs
  • Alternative RNA Splicing Increases the Number of Proteins Expressed from a Single Eukaryotic Gene
  • 4.3 Control of Gene Expression in Prokaryotes
  • Initiation of lac Operon Transcription Can Be Repressed and Activated
  • Small Molecules Regulate Expression of Many Bacterial Genes via DNA-Binding Repressors
  • Transcription by o54-RNA Polymerase Is Controlled by Activators That Bind Far from the Promoter
  • Many Bacterial Responses Are Controlled by Two-Component Regulatory Systems
  • 4.4 The Three Roles of RNA in Translation
  • Messenger RNA Carries Information from DNA in a Three-Letter Genetic Code
  • Folded Structure of tRNA Promotes Its Decoding Functions
  • Nonstandard Base Pairing Often Occurs Between Codons and Anticodons
  • Aminoacyl-tRNA Synthetases Activate Amino Acids by Covalently Linking Them to tRNAs
  • Ribosomes Are Protein-Synthesizing Machines
  • 4.5 Stepwise Synthesis of Proteins on Ribosomes
  • Methionyl-tRNAiMet Recognizes the AUG Start Codon
  • Translation Initiation Usually Occurs Near the First AUG Closest to the 5' End of an mRNA
  • During Chain Elongation Each Incoming Aminoacyl-tRNA Moves Through Three Ribosomal Sites
  • Translation Is Terminated by Release Factors When a Stop Codon Is Reached
  • Polysomes and Rapid Ribosome Recycling Increase the Efficiency of Translation
  • 4.6 DNA Replication
  • DNA Polymerases Require a Primer to Initiate Replication
  • Duplex DNA Is Unwound, and Daughter Strands Are Formed at DNA Replication Fork
  • Helicase, Primase, DNA Polymerases, and Other Proteins Participate in DNA Replication
  • DNA Replication Generally Occurs Bidirectionally from Each Origin
  • 4.7 Viruses: Parasites of the Cellular Genetic System
  • Most Viral Host Ranges Are Narrow
  • Viral Capsids Are Regular Arrays of One or a Few Types of Protein
  • Viruses Can Be Cloned and Counted in Plaque Assays --
  • Contents note continued: Lytic Viral Growth Cycles Lead to Death of Host Cells
  • Viral DNA Is Integrated into Host-Cell Genome in Some Nonlytic Viral Growth Cycles
  • 5 Biomembranes and Cell Architecture
  • 5.1 Biomembranes: Lipid Composition and Structural Organization
  • Three Classes of Lipids Are Found in Biomembranes
  • Most Lipids and Many Proteins Are Laterally Mobile in Biomembranes
  • Lipid Composition Influences the Physical Properties of Membranes
  • Membrane Lipids Are Usually Distributed Unequally in the Exoplasmic and Cytosolic Leaflets
  • Cholesterol and Sphingolipids Cluster with Specific Proteins in Membrane Microdomains
  • 5.2 Biomembranes: Protein Components and Basic Functions
  • Proteins Interact with Membranes in Three Different Ways
  • Membrane-Embedded a Helices Are the Primary Secondary Structures in Most Transmembrane Proteins
  • Multiple ß Strands in Porins Form Membrane-Spanning "Barrels"
  • Covalently Attached Hydrocarbon Chains Anchor Some Proteins to Membranes
  • All Transmembrane Proteins and Glycolipids Are Asymmetrically Oriented in the Bilayer
  • Interactions with the Cytoskeleton Impede the Mobility of Integral Membrane Proteins
  • Lipid-Binding Motifs Help Target Peripheral Proteins to the Membrane
  • Plasma Membrane Has Many Common Functions in All Cells
  • 5.3 Organelles of Eukaryotic Cell
  • Endosomes Take Up Soluble Macromolecules from the Cell Exterior
  • Lysosomes Are Acidic Organelles That Contain a Battery of Degradative Enzymes
  • Peroxisomes Degrade Fatty Acids and Toxic Compounds
  • Endoplasmic Reticulum Is a Network of Interconnected Internal Membranes
  • Golgi Complex Processes and Sorts Secreted and Membrane Proteins
  • Plant Vacuoles Store Small Molecules and Enable a Cell to Elongate Rapidly
  • Nucleus Contains the DNA Genome, RNA Synthetic Apparatus, and a Fibrous Matrix
  • Mitochondria Are the Principal Sites of ATP Production in Aerobic Cells
  • Chloroplasts Contain Internal Compartments in Which Photosynthesis Takes Place
  • 5.4 The Cytoskeleton Components a Structural Functions
  • Three Types of Filaments Compose the Cytoskeleton
  • Cytoskeletal Filaments Are Organized into Bundles and Networks
  • Microfilaments and Membrane-Binding Proteins Form a Skeleton Underlying the Plasma Membrane
  • Intermediate Filaments Support the Nuclear Membrane and Help Connect Cells into Tissues
  • Microtubules Radiate from Centrosomes and Organize Certain Subcellular Structures
  • 5.5 Purification of Cells and Their Parts
  • Flow Cytometry Separates Different Cell Types
  • Disruption of Cells Releases Their Organelles and Other Contents
  • Centrifugation Can Separate Many Types of Organelles
  • Organelle-Specific Antibodies Are Useful in Preparing Highly Purified Organelles
  • Proteins Can Be Removed from Membranes by Detergents or High-Salt Solutions
  • 5.6 Visualizing Cell Architecture
  • Microscope Detects, Magnifies, and Resolves Small Objects
  • Samples for Microscopy Must Be Fixed, Sectioned, and Stained to Image Subcellular Details
  • Phase-Contrast and Differential Interference Contrast Microscopy Visualize Unstained Living Cells
  • Fluorescence Microscopy Can Localize and Quantify Specific Molecules in Fixed and Live Cells
  • Confocal Scanning and Deconvolution Microscopy Provide Sharp Images of Three-Dimensional Objects
  • Resolution of Transmission Electron Microscopy Is Vastly Greater Than That of Light Microscopy
  • Electron Microscopy of Metal-Coated Specimens Can Reveal Surface Features of Cells and Their Components
  • Three-Dimensional Models Can Be Constructed from Microscopy Images
  • 6 Integrating Cells into Tissues
  • 6.1 Cell-Cell and Cell-Matrix Adhesion: An Overview
  • Cell-Adhesion Molecules Bind to One Another and to Intracellular Proteins
  • extracellular Matrix Participates in Adhesion and Other Functions
  • Diversity of Animal Tissues Depends on Evolution of Adhesion Molecules with Various Properties
  • 6.2 Sheetlike Epithelial Tissues: Junctions and Adhesion Molecules
  • Specialized Junctions Help Define the Structure and Function of Epithelial Cells
  • Ca2+-Dependent Homophilic Cell-Cell Adhesion in Adherens Junctions and Desmosomen Is Mediated by Cadherins
  • Tight Junctions Seal Off Body Cavities and Restrict Diffusion of Membrane Components
  • Differences in Permeability of Tight Junctions Can Control Passage of Small Molecules Across Epithelia
  • Many Cell-Matrix and Some Cell-Cell Interactions Are Mediated by Integrins
  • 6.3 The Extracellular Matrix of Epithelial Sheets
  • Basal Lamina Provides a Foundation for Epithelial Sheets
  • Sheet-Forming Type IV Collagen Is a Major Structural Component in Basal Lamina
  • Laminin, a Multiadhesive Matrix Protein, Helps Cross-link Components of the Basal Lamina
  • Secreted and Cell-Surface Proteoglycans Are Expressed by Many Cell Types
  • Modifications in Glycosaminoglycan (GAG) Chains Can Determine Proteoglycan Functions
  • 6.4 The Extracellular Matrix of Nonepithelial Tissues
  • Fibrillar Collagens Are the Major Fibrous Proteins in the Extracellular Matrix of Connective Tissues
  • Formation of Collagen Fibrils Begins in the Endoplasmic Reticulum and Is Completed Outside the Cell
  • Type I and II Collagens Form Diverse Structures and Associate with Different Nonfibrillar Collagens
  • Hyaluronan Resists Compression and Facilitates Cell Migration
  • Association of Hyaluronan and Proteoglycans Forms Large, Complex Aggregates
  • Fibronectins Connect Many Cells to Fibrous Collagens and Other Matrix Components
  • 6.5 Adhesive Interactions and Nonepithelial Cells
  • Integrin-Containing Adhesive Structures Physically and Functionally Connect the ECM and Cytoskeleton in Nonepithelial Cells
  • Diversity of Ligand-Integrin Interactions Contributes to Numerous Biological Processes
  • Cell-Matrix Adhesion Is Modulated by Changes in the Binding Activity and Numbers of Integrins
  • Molecular Connections between the ECM and the Cytoskeleton Are Defective in Muscular Dystrophy
  • Cat+-Independent Cell-Cell Adhesion in Neuronal and Other Tissues Is Mediated by CAMs in the Immunoglobulin Superfamily
  • Movement of Leukocytes into Tissues Depends on a Precise Sequence of Combinatorially Diverse Sets of Adhesive Interactions
  • Gap Junctions Composed of Connexins Allow Small Molecules to Pass Between Adjacent Cells
  • 6.6 Plant Tissues
  • Plant Cell Wall Is a Laminate of Cellulose Fibrils in a Matrix of Glycoproteins
  • Loosening of the Cell Wall Permits Elongation of Plant Cells
  • Plasmodesmata Directly Connect the Cytosols of Adjacent Cells in Higher Plants
  • Only a Few Adhesive Molecules Have Been Identified in Plants
  • 6.7 Growth and Use of Cultured Cells
  • Culture of Animal Cells Requires Nutrient-Rich Media and Special Solid Surfaces
  • Primary Cell Cultures and Cell Strains Have a Finite Life Span
  • Transformed Cells Can Grow Indefinitely in Culture
  • Hybrid Cells Called Hybridomas Produce Abundant Monoclonal Antibodies
  • HAT Medium Is Commonly Used to Isolate Hybrid Cells
  • 7 Transport of Ions and Small Molecules Across Cell Membranes
  • 7.1 Overview of Membrane Transport
  • Few Molecules Cross Membranes by Passive Diffusion
  • Membrane Proteins Mediate Transport of Most Molecules and All Ions Across Biomembranes
  • Several Features Distinguish Uniport Transport from Passive Diffusion
  • GLUT1 Uniporter Transports Glucose into Most Mammalian Cells
  • Human Genome Encodes a Family of Sugar Transporting GLUT Proteins
  • Transport Proteins Can Be Enriched Within Artificial Membranes and Cells
  • 7.2 ATP-Powered Rumps and the Intracellular Ionic Environnent
  • Different Classes of Pumps Exhibit Characteristic Structural and Functional Properties
  • ATP-Driven Ion Pumps Generate and Maintain Ionic Gradients Across Cellular Membranes
  • Muscle Cat+ ATPase Pumps Cat+ Ions from the Cytosol into the Sarcoplasmic Reticulum
  • Calmodulin-Mediated Activation of Plasma-Membrane Cat+ ATPase Leads to Rapid Cat+ Export
  • Na+/K+ ATPase Maintains the Intracellular Na+ and K+ Concentrations in Animal Cells
  • V -Class H+ ATPases Pump Protons Across Lysosomal and Vacuolar Membranes
  • Bacterial Permeases Are ABC Proteins That Import a Variety of Nutrients from the Environment
  • About 50 ABC Small-Molecule Pumps Are Known in Mammals
  • ABC Proteins That Transport Lipid-Soluble Substrates May Operate by a Flippase Mechanism
  • 7.3 Nongated Ion Channels and the Resting Membrane Potential
  • Selective Movement of Ions Creates a Transmembrane Electric Potential Difference
  • Membrane Potential in Animal Cells Depends Largely on Resting K+ Channels
  • Ion Channels Contain a Selectivity Filter Formed from Conserved Transmembrane a Helices and P Segments
  • Patch Clamps Permit Measurement of Ion Movements Through Single Channels
  • Novel Ion Channels Can Be Characterized by a Combination of Oocyte Expression and Patch Clamping
  • Na+ Entry into Mammalian Cells Has a Negative Change in Free Energy (LIG)
  • 7.4 Cotransport by Symporters and Antiporters
  • Na+-Linked Symporters Import Amino Acids and Glucose into Animal Cells Against High Concentration Gradients
  • Na+-Linked Antiporter Exports Cat2+ from Cardiac Muscle Cells
  • Several Cotransporters Regulate Cytosolic pH
  • Numerous Transport Proteins Enable Plant Vacuoles to Accumulate Metabolites and Ions
  • 7.5 Movement of Water
  • Osmotic Pressure Causes Water to Move Across Membranes
  • Different Cells Have Various Mechanisms for Controlling Cell Volume
  • Aquaporins Increase the Water Permeability of Cell Membranes
  • 7.6 Transepithelial Transport
  • Multiple Transport Proteins Are Needed to Move Glucose and Amino Acids Across Epithelia --
  • Contents note continued: Simple Rehydration Therapy Depends on the Osmotic Gradient Created by Absorption of Glucose and Na+
  • Parietal Cells Acidify the Stomach Contents While Maintaining a Neutral Cytosolic pH
  • 7.7 Voltage Gated Ion Channels and the Propagation of Action Potentials in Nerve Cells
  • Specialized Regions of Neurons Carry Out Different Functions
  • Magnitude of the Action Potential Is Close to ENa
  • Sequential Opening and Closing of Voltage-Gated Na+ and K+ Channels Generate Action Potentials
  • Action Potentials Are Propagated Unidirectionally Without Diminution
  • Nerve Cells Can Conduct Many Action Potentials in the Absence of ATP
  • All Voltage-Gated Ion Channels Have Similar Structures
  • Voltage-Sensing S4 α Helices Move in Response to Membrane Depolarization
  • Movement of the Channel-Inactivating Segment into the Open Pore Blocks Ion Flow
  • Myelination Increases the Velocity of Impulse Conduction
  • Action Potentials "Jump" from Node to Node in Myelinated Axons
  • 7.8 Neurotransmitters and Receptor and Transport Proteins in Signal Transmission at Synapses
  • Neurotransmitters Are Transported into Synaptic Vesicles by H+-Linked Antiport Proteins
  • Influx of Ca2+ Through Voltage-Gated Cat+ Channels Triggers Release of Neurotransmitters
  • Signaling at Synapses Usually Is Terminated by Degradation or Reuptake of Neurotransmitters
  • Opening of Acetylcholine-Gated Cation Channels Leads to Muscle Contraction
  • All Five Subunits in the Nicotinic Acetylcholine Receptor Contribute to the Ion Channel
  • Nerve Cells Make an All-or-None Decision to Generate and Action Potential
  • Nervous System Uses Signaling Circuits Composed of Multiple Neurons
  • 8 Cellular Energetics
  • 8.1 Oxidation of Glucose and Fatty Acids to CO2
  • Cytolysis Enzymes Convert Glucose into Pyruvate in Glycolysis
  • Anaerobic Metabolism of Each Glucose Molecule Yields Only Two ATP Molecules
  • Mitochondria Possess Two Structurally and Functionally Distinct Membranes
  • Acetyl CoA Derived from Pyruvate Is Oxidized to Yield CO2 and Reduced Coenzymes in Mitochondria
  • Transporters in the Inner Mitochondrial Membrane Allow the Uptake of Electrons from Cytosolic NADH
  • Mitochondrial Oxidation of Fatty Acids Is Coupled to ATP Formation
  • Peroxisomal Oxidation of Fatty Acids Generates No ATP
  • Rate of Glucose Oxidation Is Adjusted to Meet the Cell's Need for ATP
  • 8.2 Electron Transport and Generation of the Proton-Motive Force
  • 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 through a Series of Four Multiprotein Complexes
  • 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
  • Q Cycle Increases the Number of Protons Translocated as Electrons Flow Through the CoQH2-Cytochrome c Reductase Complex
  • 8.3 Harnessing the Proton-Motive Force for Energy-Requiring Processes
  • Bacterial Plasma-Membrane Proteins Catalyze Electron Transport and Coupled ATP Synthesis
  • ATP Synthase Comprises Two Multiprotein Complexes Termed F0 and F1
  • Rotation of the F1 γ Subunit, Driven by Proton Movement Through F0, Powers ATP Synthesis
  • ATP-ADP Exchange Across the Inner Mitochondrial Membrane Is Powered by the Proton-Motive Force
  • Rate of Mitochondrial Oxidation Normally Depends on ADP Levels
  • Brown-Fat Mitochondria Contain an Uncoupler of Oxidative Phosphorylation
  • 8.4 Photosynthetic Stages and Light-Absorbing Pigments
  • Thylakoid Membranes Are the Sites of Photosynthesis in Plants
  • Three of the Four Stages in Photosynthesis Occur Only During Illumination
  • Each Photon of Light Has a Defined Amount of Energy
  • Photosystems Comprise a Reaction Center and Associated Light-Harvesting Complexes
  • Photoelectron Transport from Energized Reaction Center Chlorophyll a Produces a Charge Separation
  • Light-Harvesting Complexes Increase the Efficiency of Photosynthesis
  • 8.5 Molecular Analysis of Photosystems
  • Single Photosystem of Purple Bacteria Generates a Proton-Motive Force but No 02
  • Chloroplasts Contain Two Functionally and Spatially Distinct Photosystems
  • Linear Electron Flow Through Both Plant Photosystems, PSII and PSI, Generates a Proton-Motive Force, O2, and NADPH
  • Oxygen-Evolving Complex Is Located on the Luminal Surface of the PSII Reaction Center
  • Cyclic Electron Flow Through PSI Generates a Proton-Motive Force but No NADPH or O2
  • Relative Activity of Photosystems I and II Is Regulated
  • 8.6 CO2 Metabolism During Photosynthesis
  • CO2 Fixation Occurs in the Chloroplast Stroma
  • Synthesis of Sucrose Incorporating Fixed CO2 Is Completed in the Cytosol
  • Light and Rubisco Activase Stimulate CO2 Fixation
  • Photorespiration, Which Competes with Photosynthesis, Is Reduced in Plants That Fix CO2 by the C4 Pathway
  • Sucrose Is Transported from Leaves Through the Phloem to All Plant Tissues
  • 9 Molecular Genetic Techniques and Genomics
  • 9.1 Genetic Analysis of Mutations to Identify and Study Genes
  • Recessive and Dominant Mutant Alleles Generally Have Opposite Effects on Gene Function
  • Segregation of Mutations in Breeding Experiments Reveals Their Dominance or Recessivity
  • Conditional Mutations Can Be Used to Study Essential Genes in Yeast
  • Recessive Lethal Mutations in Diploids Can Be Identified by Inbreeding and Maintained in Heterozygotes
  • Complementation Tests Determine Whether Different Recessive Mutations Are in the Same Gene
  • Double Mutants Are Useful in Assessing the Order in Which Proteins Function
  • Genetic Suppression and Synthetic Lethality Can Reveal Interacting or Redundant Proteins
  • 9.2 DNA Cloning by Recombinant DNA Methods
  • Restriction Enzymes and DNA Ligases Allow Insertion of DNA Fragments into Cloning Vectors
  • E. coli Plasmid Vectors Are Suitable for Cloning Isolated DNA Fragments
  • Bacteriophage λ Vectors Permit Efficient Construction of Large DNA Libraries
  • cDNAs Prepared by Reverse Transcription of Cellular mRNAs Can Be Cloned to Generate cDNA Libraries
  • DNA Libraries Can Be Screened by Hybridization to an Oligonucleotide Probe
  • Oligonucleotide Probes Are Designed Based on Partial Protein Sequences
  • Yeast Genomic Libraries Can Be Constructed with Shuttle Vectors and Screened by Functional Complementation
  • 9.3 Characterizing and Using Cloned DNA Fragments
  • Gel Electrophoresis Allows Separation of Vector DNA from Cloned Fragments
  • Cloned DNA Molecules Are Sequenced Rapidly by the Dideoxy Chain-Termination Method
  • Polymerase Chain Reaction Amplifies a Specific DNA Sequence from a Complex Mixture
  • Blotting Techniques Permit Detection of Specific DNA Fragments and mRNAs with DNA Probes
  • E. coli Expression Systems Can Produce Large Quantities of Proteins from Cloned Genes
  • Plasmid Expression Vectors Can Be Designed for Use in Animal Cells
  • 9.4 Genomics: Genome-wide Analysis of Gene Structure and Expression
  • Stored Sequences Suggest Functions of Newly Identified Genes and Proteins
  • Comparison of Related Sequences from Different Species Can Give Clues to Evolutionary Relationships Among Proteins
  • Genes Can Be Identified Within Genomic DNA Sequences
  • Size of an Organism's Genome Is Not Directly Related to Its Biological Complexity
  • DNA Microarrays Can Be Used to Evaluate the Expression of Many Genes at One Time
  • Cluster Analysis of Multiple Expression Experiments Identifies Co-regulated Genes
  • 9.5 Inactivating the Function of Specific Genes in Eukaryotes
  • Normal Yeast Genes Can Be Replaced with Mutant Alleles by Homologous Recombination
  • Transcription of Genes Ligated to a Regulated Promoter Can Be Controlled Experimentally
  • Specific Genes Can Be Permanently Inactivated in the Germ Line of Mice
  • Somatic Cell Recombination Can Inactivate Genes in Specific Tissues
  • Dominant-Negative Alleles Can Functionally Inhibit Some Genes
  • Double-Stranded RNA Molecules Can Interfere with Gene Function by Targeting mRNA for Destruction
  • 9.6 Identifying and Locating Human Disease Genes
  • Many Inherited Diseases Show One of Three Major Patterns of Inheritance
  • Recombinational Analysis Can Position Genes on a Chromosome
  • DNA Polymorphisms Are Used in Linkage-Mapping Human Mutations
  • Linkage Studies Can Map Disease Genes with a Resolution of About 1 Centimorgan
  • Further Analysis Is Needed to Locate a Diseases Result Cloned DNA
  • Many Inherited Diseases Result from Multiple Genetic Defects
  • 10 Molecular Structure of Genes and Chromosomes
  • 10.1 Molecular Definition of a Gene
  • Most Eukaryotic Genes Produce Monocistronic mRNAs and Contain Lengthy Introns
  • Simple and Complex Transcription Units Are Found in Eukaryotic Genomes
  • 10.2 Chromosomal Organization of Genes and Noncoding DNA
  • Genomes of Many Organisms Contain Much Nonfunctional DNA
  • Protein-Coding Genes May Be Solitary or Belong to a Gene Family
  • Tandemly Repeated Genes Encode rRNAs, tRNAs, and Histones
  • Most Simple-Sequence DNAs Are Concentrated in Specific Chromosomal Locations
  • DNA Fingerprinting Depends on Differences in length of Simple-Sequence DNAs
  • 10.3 Mobile DNA
  • Movement of Mobile Elements Involves a DNA or an RNA Intermediate
  • Mobile Elements That Move As DNA Are Present in Prokaryotes and Eukaryotes
  • Some Retrotransposons Contain LTRs and Behave like Intracellular Retroviruses
  • Retrotransposons That Lack LTRs Move by a Distinct Mechanism
  • Mobile DNA Elements Probably Had a Significant Influence on Evolution
  • 10.4 Structural Organization of Eukaryotic Chromosomes --
  • Contents note continued: Eukaryotic Nuclear DNA Associates with Histone Proteins to Form Chromatin
  • Chromatin Exists in Extended and Condensed Forms
  • Modification of Histone Tails Controls Chromatin Condensation
  • Nonhistone Proteins Provide a Structural Scaffold for Long Chromatin Loops
  • Chromatin Contains Small Amounts of Other Proteins in Addition to Histones and Scaffold Proteins
  • Eukaryotic Chromosomes Contain One Linear DNA Molecule
  • 10.5 Morphology and Functional Elements of Eukaryotic Chromosomes
  • Chromosome Number, Size, and Shape at Metaphase Are Species-Specific
  • During Metaphase, Chromosomes Can Be Distinguished by Banding Patterns and Chromosome Painting
  • Interphase Polytene Chromosomes Arise by DNA Amplification
  • Heterochromatin Consists of Chromosome Regions That Do Not Uncoil
  • Three Functional Elements Are Required for Replication and Stable Inheritance of Chromosomes
  • Centromere Sequences Vary Greatly in Length
  • Addition of Telomeric Sequences by Telomerase Prevents Shortening of Chromosomes
  • Yeast Artificial Chromosomes Can Be Used to Clone Megabase DNA Fragments
  • 10.6 Organelle DNAs
  • Mitochondria Contain Multiple mtDNA Molecules
  • mtDNA Is Inherited Cytoplasmically and Encodes rRNAs, tRNAs, and Some Mitochondrial Proteins
  • 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 Humans
  • Chloroplasts Contain Large Circular DNAs Encoding More Than a Hundred Proteins
  • 11 Transcriptional Control of Gene Expression
  • 11.1 Overview of Eukaryotic Gene Control and RNA Polymerases
  • 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
  • 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
  • 11.2 Regulatory Sequences in Protein-Coding Genes
  • TATA Box, Initiators, and CpG Islands Function as Promoters in Eukaryotic DNA
  • Promoter-Proximal Elements Help Regulate Eukaryotic Genes
  • Distant Enhancers Often Stimulate Transcription by RNA Polymerase II
  • Most Eukaryotic Genes Are Regulated by Multiple Transcription-Control Elements
  • 11.3 Activators and Repressors of Transcription
  • Footprinting and Gel-Shift Assays Detect Protein-DNA Interactions
  • Activators Are Modular Proteins Composed of Distinct Functional Domains
  • Repressors Are the Functional Converse of Activators
  • DNA-Binding Domains Can Be Classified into Numerous Structural Types
  • Transcription-Factor Interactions Increase Gene-Control Options
  • Structurally Diverse Activation and Repression Domains Regulate Transcription
  • Multiprotein Complexes Form on Enhancers
  • 11.4 Transcription Initiation by RNA Polymerase II
  • General Transcription Factors Position RNA Polymerases II at Start Sites and Assist in Initiation
  • Sequential Assembly of Proteins Forms the Pol II Transcription Preinitiation Complex in Vitro
  • In Vivo Transcription Initiation by Pol II Requires Additional Proteins
  • 11.5 Molecular Mechanisms of Transcription Activation and Repression
  • Formation of Heterochromatin Silences Gene Expression at Telomeres, near Centromeres, and in Other Regions
  • Repressors Can Direct Histone Deacetylation at Specific Genes
  • Activators Can Direct Histone Acetylation at Specific Genes
  • Modifications of Specific Residues in Histone Tails Control Chromatin Condensation
  • Chromatin-Remodeling Factors Help Activate or Repress Some Genes
  • Mediator Complex Forms a Molecular Bridge Between Activation Domains and Pol II
  • Transcription of Many Genes Requires Ordered Binding of Activators and Action of Co-Activators
  • Yeast Two-Hybrid System Exploits Activator Flexibility to Detect cDNAs That Encode Interacting Proteins
  • 11.6 Regulation of Transcription-Factor Activity
  • All Nuclear Receptors Share a Common Domain Activity Structure
  • Nuclear-Receptor Response Elements Contain Inverted or Direct Repeats
  • Hormone Binding to a Nuclear Receptor Regulates Its Activity as a Transcription Factor
  • 11.7 Regulation Elongation and Termination of Transcription
  • Transcription of the HIV Genome Is Regulated by an Antitermination Mechanism
  • Promoter-Proximal Pausing of RNA Polymerase II Occurs in Some Rapidly Induced Genes
  • 11.8 Other Eukaryotic Transcription Systems
  • Transcription Initiation by Pol I and Pol III Is Analogous to That by Pol II
  • Mitochondrial and Chloroplast DNAs Are Transcribed by Organelle-Specific RNA Polymerases
  • 12 Post-transcriptional Gene Control and Nuclear Transport
  • 12.1 Processing of Eukaryotic Pre-mRNA
  • 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
  • 3' Cleavage and Polyadenylation of Pre-mRNAs Are Tightly Coupled
  • Splicing Occurs at Short, Conserved Sequences in Pre-mRNAs via Two Transesterification Reactions
  • snRNAs Base-Pair with Pre-mRNA and with One Another During Splicing
  • Spliceosomes, Assembled from snRNPs and a Pre-RNA, Carry Out Splicing
  • Chain Elongation by RNA Polymerase II Is Coupled to the Presence of RNA-Processing Factors
  • SR Proteins Contribute to Exon Definition in Long Pre-mRNAs
  • 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
  • Nuclear Exonucleases Degrade RNA That Is Processed out of Pre-mRNAs
  • 12.2 Regulation of Pre-mRNA Processing
  • Alternative Splicing Is the Primary Mechanism for Regulating mRNA Processing
  • Cascade of Regulated RNA Splicing Controls Drosophila Sexual Differentiation
  • Splicing Repressors and Activators Control Splicing at Alternative Sites
  • RNA Editing Alters the Sequences of Pre-mRNAs
  • 12.3 Macromolecular Transport Across the Nuclear Envelope
  • Large and Small Molecules Enter and Leave the Nucleus via Nuclear Pore Complexes
  • Importins Transport Proteins Containing Nuclear-Localization Signals into the Nucleus
  • Exportins Transport Proteins Containing Nuclear-Export Signals out of the Nucleus
  • Control of Some Genes Is Achieved by Regulating Transport of Transcription Factors
  • Most mRNAs Are Exported from the Nucleus with the Aid of an mRNA-Exporter
  • Pre-mRNAs in Spliceosomes Are Not Exported from the Nucleus
  • HIV Rev Protein Regulates the Transport of Unspliced Viral mRNAs
  • 12.4 Cytoplasmic Mechanisms of Post-transcriptional Control
  • Micro RNAs Repress Translation of Specific mRNAs
  • RNA Interference Induces Degradation of mRNAs with Sequences Complementary to Double-Stranded RNAs
  • Cytoplasmic Polyadenylation Promotes Translation of Some mRNAs
  • mRNAs Are Degraded by Several Mechanisms in the Cytoplasm
  • Iron-Sensitive RNA-Binding Protein Regulates mRNA Translation and Degradation
  • Nonsense-Mediated Decay and Other mRNA Surveillance Mechanisms Prevent Translation of Improperly Processed mRNAs
  • Localization of mRNAs Permits Production of Proteins at Specific Regions Within the Cytoplasm
  • 12.5 Processing of rRNA and tRNA
  • Pre-rRNA Genes Are Similar in All Eukaryotes and Function as Nucleolar Organizers
  • Small Nucleolar RNAs Assist in Processing Pre-rRNAs and Assembling Ribosome Subunits
  • Self-Splicing Group I Introns Were the First Examples of Catalytic RNA
  • Pre-tRNAs Undergo Cleavage, Base Modification, and Sometimes Protein-Catalyzed Splicing
  • 13 Signaling at the Cell Surface
  • 13.1 Signaling Molecules and Cell-Surface Receptors
  • Signaling Molecules in Animals Operate over Various Distances
  • Receptors Activate a Limited Number of Signaling Pathways
  • Receptor Proteins Exhibit Ligand-Binding and Effector Specificity
  • Maximal Cellular Response to a Signaling Molecule May Not Require Activation of All Receptors
  • Sensitivity of a Cell to External Signals Is Determined by the Number of Surface Receptors
  • Binding Assays Are Used to Detect Receptors and Determine Their Kd Values
  • Receptors Can Be Purified by Affinity Techniques or Expressed from Cloned Genes
  • 13.2 Intracellular Signal Transduction
  • Second Messengers Carry Signals from Many Receptors
  • Many Conserved Intracellular Proteins Function in Signal Transduction
  • Some Receptors and Signal-Transduction Proteins Are Localized
  • Appropriate Cellular Responses Depend on Interaction and Regulation of Signaling Pathways
  • 13.3 G Protein-Coupled Receptors That Activate or Inhibit Adenylyl Cyclase
  • Ga Subunit of G Proteins Cycles Between Active and Inactive Forms
  • Epinephrine Binds to Several Different G Protein-Coupled Receptors
  • Critical Functional Domains in Receptors and Coupled G Proteins Have Been Identified
  • Adenylyl Cyclase Is Stimulated and Inhibited by Different Receptor-Ligand Complexes
  • cAMP-Activated Protein Kinase A Mediates Various Responses in Different Cells
  • Glycogen Metabolism Is Regulated by Hormone Induced Activation of Protein Kinase A
  • Signal Amplification Commonly Occurs Downstream from Cell-Surface Receptors
  • Several Mechanisms Regulate Signaling from G Protein-Coupled Receptors
  • Anchoring Proteins Localize Effects of cAMP to Specific Subcellular Regions
  • 13.4 G Protein-Coupled Receptors That Regulate Ion Channels
  • Cardiac Muscarinic Acetylcholine Receptors Activate a G Protein That Opens K+ Channels --
  • Contents note continued: Gt-Coupled Receptors Are Activated by Light
  • Activation of Rhodopsin Induces Closing of cGMP-Gated Cation Channels
  • Rod Cells Adapt to Varying Levels of Ambient Light
  • 13.5 G protein-Coupled Receptors That Activate Phospholipase C
  • Inositol 1,4,5-Trisphosphate (IP3) Triggers Release of Cat+ from the Endoplasmic Reticulum
  • Diacylglycerol (DAG) Activates Protein Kinase C, Which Regulates Many Other Proteins
  • Ca2t+/Calmodulin Complex Mediates Many Cellular Responses
  • Signal-Induced Relaxation of Vascular Smooth Muscle Is Mediated by cGMP-Activated Protein Kinase G
  • 13.6 Activation of Gene Transcription by G Protein-Coupled Receptors
  • Membrane-Localized Tubby Transcription Factor Is Released by Activation of Phospholipase C
  • CREB Links cAMP Signals to Transcription
  • GPCR-Bound Arrestin Activates Several Kinase Cascades That Control Gene Expression
  • 14 Signaling Pathways That Control Gene Activity
  • 14.1 TGFB Receptors and the Direct Activation of Smads
  • TGFß Is Formed by Cleavage of a Secreted Inactive Precursor
  • TGFß Signaling Receptors Have Serine/Threonine Kinase Activity
  • Activated Type I TGFß Receptors Phosphorylase Smad Transcription Factors
  • Oncoproteins and I-Smads Regulate Smad Signaling via Negative Feedback Loops
  • Loss of TGFß Signaling Contributes to Abnormal Cell Proliferation and Malignancy
  • 14.2 Cytokine Receptors and the JAK-STAT Pathway
  • Cytokine Receptors and Receptor Tyrosine Kinases Share Many Signaling Features
  • Cytokines Influence Development of Many Cell Types
  • All Cytokines and Their Receptors Have Similar Structures and Activate Similar Signaling Pathways
  • Somatic Cell Genetics Revealed JAKs and STATS as Essential Signal-Transduction Proteins
  • Receptor-Associated JAK Kinases Activate STAT Transcription Factors Bound to a Cytokine Receptor
  • SH2 and PTB Domains Bind to Specific Sequences Surrounding Phosphotyrosine Residues
  • Signaling from Cytokine Receptors Is Modulated by Negative Signals
  • Mutant Erythropoietin Receptor That Cannot Be Down-Regulated Leads to Increased Hematocrit
  • 14.3 Receptor Tyrosine Kinases and Activation of Ras
  • Ligand Binding Leads to Transphosphorylation of Receptor Tyrosine Kinases
  • Ras, a GTPase Switch Protein, Cycles Between Active and Inactive States
  • Adapter Protein and Guanine Nucleotide Exchange Factor Link Most Activated Receptor Tyrosine Kinases to Ras
  • Genetic Studies in Drosophile Identify Key Signal-Transducing Proteins Downstream from Receptor Tyrosine Kinases
  • Binding of Sos Protein to Inactive Ras Causes a Conformational Change That Activates Ras
  • 14.4 MAP Kinase Pathways
  • Signals Pass from Activated Ras to a Cascade of Protein Kinases
  • MAP Kinase Regulates the Activity of Many Transcription Factors Controlling Early-Response Genes
  • G Protein-Coupled Receptors Transmit Signals to MAP Kinase in Yeast Mating Pathways
  • Scaffold Proteins Isolate Multiple MAP Kinase Pathways in Eukaryotic Cells
  • 14.5 Phosphoinositides as Signal Transducers
  • Phospholipase C Is Activated by Some RTKs and Cytokine Receptors
  • Recruitment of PI-3 Kinase to Hormone-Stimulated Receptors Leads to Activation of Protein Kinase B
  • Insulin Receptor Acts Through the PI-3 Kinase Pathway to Lower Blood Glucose
  • Activated Protein Kinase B Promotes Cell Survival by Several Pathways
  • PTEN Phosphatase Terminates Signaling via the PI-3 Kinase Pathway
  • Receptor for a Particular Growth Factor Often Is linked to Multiple Signaling Pathways
  • 14.6 Pathways That Involve Signal-Induced Protein Cleavage
  • Signal-Induced Degradation of a Cytosolic Inhibitor Protein Activates the NF-KB Transcription Factor
  • Regulated Intramembrane Proteolysis Catalyzed by Presenilin 1 Activates Notch Receptor
  • 14.7 Down-Modulation of Receptor Signaling
  • Endocytosis of Cell-Surface Receptors Desensitizes Cells to Many Hormones
  • Secreted Decoy Receptors Bind Hormone and Prevent Receptor Activation
  • 15 Integration of Signals and Gene Controls
  • 15.1 Experimental Approaches for Building a Comprehensive View of Signal-Induced Responses
  • Genomic Analyses Show Evolutionary Conservation and Proliferation of Genes Encoding Signals and Regulators
  • In Situ Hybridization Can Detect Transcription Changes in Intact Tissues and Permeabilized Embryos
  • DNA Microarray Analysis Can Assess Expression of Multiple Genes Simultaneously
  • Protein Microarrays Are Promising Tools for Monitoring Cell Responses That Include Changes in Protein-Binding Patterns
  • Systematic Gene Inactivation by RNA Interference
  • 15.2 Responses of Cells to Environmental Influences
  • Integration of Multiple Second Messengers Regulates Glycogenolysis
  • Insulin and Glucagon Work Together to Maintain a Stable Blood Glucose Level
  • Oxygen Deprivation Induces a Program of Cellular Responses
  • 15.3 Control of Cell Fates by Graded Amounts of Regulators
  • Inductive Signaling Operates by Gradient and Relay Mechanisms
  • Morphogens Control Cell Fates in Early Drosophila Development
  • Reciprocal Signaling Between the Oocyte and Follicle Cells Establishes Initial Dorsovental Patterning in Drosophila
  • Nuclear Dorsal and Decapentaplegic, a Secreted Signal, Specify Ventral and Dorsal Cell Fates
  • Transcriptional Control by Maternally Derived Bicoid Protein Specifies the Embryo's Anterior
  • Maternally Derived Translation Inhibitors Reinforce Bicoid-Mediated Anterioposterior Patterning
  • Toll-like Signaling Activates an Ancient Defense System in Plants and Animals
  • 15.4 Boundary Creation by Different Combinations of Transcription Factors
  • Drosophila Gap Genes Are Transcribed in Broad Bands of Cells and Regulate One Another
  • Combinations of Gap Proteins Direct Transcription of Pair-Rule Genes in Stripes
  • Maternal and Zygotic Segmentation Proteins Regulate Expression of Homeotic (Hox) Genes
  • Flower Development Also Requires Spatially Regulated Production of Transcription Factors
  • 15.5 Boundary Creation by Extracellular Signals
  • Two Secreted Signals, Wingless and Hedgehog, Create Additional Boundaries Within Segments of Cellular Fly Embryos
  • Signaling, Which Requires Two Transmembrane Proteins, Relieves Repression of Target Genes
  • Wnt Signals Trigger Disassembly of an Intracellular Complex, Releasing a Transcription Factor
  • Gradients of Hedgehog and Transforming Growth Factor ß Specify Cell Types in the Neural Tube
  • Cell-Surface Proteoglycans Influence Signaling by Some Pathways
  • 15.6 Reciprocal Induction and Lateral Inhibition
  • Cell-Surface Ephrin Ligands and Receptors Mediate Reciprocal Induction During Angiogenesis
  • Conserved Notch Signaling Pathway Mediates Lateral Inhibition
  • 15.7 Integrating and Controlling Signals
  • Competence Depends on Properties of Cells That Enable Them to Respond to Inductive Signals
  • Some Signals Can Induce Diverse Cellular Responses
  • Limb Development Depends on Integration of Multiple Extracellular Signal Gradients
  • Signals Are Buffered by Intracellular and Extracellular Antagonists
  • 16 Moving Proteins into Membranes and Organelles
  • 16.1 Translocation of Secretory Proteins Across the ER Membrane
  • Hydrophobic N-Terminal Signal Sequence Targets Nascent Secretory Proteins to the ER
  • Cotranslational Translocation Is Initiated by Two GTP-Hydrolyzing Proteins
  • Passage of Growing Polypeptides Through the Translocon Is Driven by Energy Released During Translation
  • ATP Hydrolysis Powers Post-translational Translocation of Some Secretory Proteins in Yeast
  • 16.2 Insertion of Proteins into the ER Membrane
  • Several topological Classes of Integral Membrane Proteins Are Synthesized on the ER
  • Internal Stop-Transfer and Signal-Anchor Sequences Determine Topology of Single-Pass Proteins
  • Multipass Proteins Have Multiple Internal Topogenic Sequences
  • Phospholipid Anchor Tethers Some Cell-Surface Proteins to the Membrane
  • Topology of a Membrane Protein Often Can Be Deduced from Its Sequence
  • 16.3 Protein Modifications, Folding, and Quality Control in the ER
  • Preformed N-Linked Oligosaccharide Is Added to Many Proteins in the Rough ER
  • Oligosaccharide Side Chains May Promote Folding and Stability of Glycoproteins
  • Disulfide Bonds Are Formed and Rearranged by Proteins in the ER Lumen
  • Chaperones and Other ER Proteins Facilitate Folding and Assembly of Proteins
  • Improperly Folded Proteins in the ER Induce Expression of Protein-Folding Catalysts
  • Unassembled or Misfolded Proteins in the ER Are Often Transported to the Cytosol for Degradation
  • 16.4 Export of Bacterial Proteins
  • Cytosolic SecA ATPase Pushes Bacterial Polypeptides Through Translocons into the Periplasmic Space
  • Several Mechanisms Translocate Bacterial Proteins into the Extracellular Space
  • Pathogenic Bacteria Can Inject Proteins into Animal Cells via Type III Secretion Apparatus
  • 16.5 Sorting of Proteins to Mitochrondria and Chloroplasts
  • Amphipathic N-Terminal Signal Sequences Direct Proteins to the Mitochondrial Matrix
  • Mitochondrial Protein Import Requires Outer Membrane Receptors and Translocons in Both Membranes
  • Studies with Chimeric Proteins Demonstrate Important Features of Mitochondrial Import
  • Three Energy Inputs Are Needed to Import Proteins into Mitochondria
  • Multiple Signals and Pathways Target Proteins to Submitochondrial Compartments
  • Targeting of Chloroplast Stromal Proteins Is Similar to Import of Mitochondrial Matrix Proteins
  • Proteins Are Targeted to Thylakoids by Mechanisms Related to Translocation Across the Bacterial Inner Membrane
  • 16.6 Sorting of Peroxisomal Proteins
  • Cytosolic Receptor Targets Proteins with an SKL Sequence at the C-Terminus into the Peroxisomal Matrix --
  • Contents note continued: Peroxisomal Membrane and Matrix Proteins Are Incorporated by Different Pathways
  • 17 Vesicular Traffic, Secretion, and Endocytosis
  • 17.1 Techniques for Studying the Secretory Pathway
  • Transport of a Protein Through the Secretory Pathway Can Be Assayed in Living Cells
  • Yeast Mutants Define Major Stages and Many Components in Vesicular Transport
  • Cell-free Transport Assays Allow Dissection of Individual Steps in Vesicular Transport
  • 17.2 Molecular Mechanisms of Vesicular Traffic
  • Assembly of a Protein Coat Drives Vesicle Formation and Selection of Cargo Molecules
  • Conserved Set of GTPase Switch Proteins Controls Assembly of Different Vesicle Coats
  • Targeting Sequences on Cargo Proteins Make Specific Molecular Contacts with Coat Proteins
  • Rab GTPases Control Docking of Vesicles on Target Membranes
  • Paired Sets of SNARE Proteins Mediate Fusion of Vesicles with Target Membranes
  • Dissociation of SNARE Complexes After Membrane Fusion Is Driven by ATP Hydrolysis
  • Conformational Changes in Viral Envelope Proteins Trigger Membrane Fusion
  • 17.3 Early Stages of the Secretory Pathway
  • COPII Vesicles Mediate Transport from the ER to the Golgi
  • COPI Vesicles Mediate Retrograde Transport within the Golgi and from the Golgi to the ER
  • Anterograde Transport Through the Golgi Occurs by Cisternal Progression
  • 17.4 Later Stages of the Secretory Pathway
  • Vesicles Coated with Clathrin and/or Adapter Proteins Mediate Several Transport Steps
  • Dynamin Is Required for Pinching Off of Clathrin Vesicles
  • Mannose 6-Phosphate Residues Target Soluble Proteins to Lysosomes
  • Study of Lysosomal Storage Diseases Revealed Key Components of the Lysosomal Sorting Pathway
  • Protein Aggregation in the Trans-Golgi May Function in Sorting Proteins to Regulated Secretory Vesicles
  • Some Proteins Undergo Proteolytic Processing After Leaving the Trans-Golgi
  • Several Pathways Sort Membrane Proteins to the Apical or Basolateral Region of Polarized Cells
  • 17.5 Receptor-Mediated Endocytosis and the Sorting of Internalized Proteins
  • Receptors for Low-Density Lipoprotein and Other Ligands Contain Sorting Signals That Target Them for Endocytosis
  • Acidic pH of Late Endosomes Causes Most Receptor-Ligand Complexes to Dissociate
  • Endocytic Pathway Delivers Iron to Cells Without Dissociation of Receptor-Transferrin Complex Endosomes
  • Specialized Vesicles Deliver Cell Components to the Lysosome for Degradation
  • Retroviruses Bud from the Plasma Membrane by a Process Similar to Formation of Multivesicular Endosomes
  • Transcytosis Moves Some Endocytosed Ligands Across an Epithelial Cell Layer
  • 17.6 Synaptic Vesicle Function and Formation
  • Synaptic Vesicles Loaded with Neurotransmitter Are Localized Near the Plasma Membrane
  • Calcium-Binding Protein Regulates Fusion of Synaptic Vesicles with the Plasma Membrane
  • Fly Mutants Lacking Dynamin Cannot Recycle Synaptic Vesicles
  • 18 Metabolism and Movement of Lipids
  • 18.1 Phospholipids and Sphingolìpids: Synthesis and Intracellular Movement
  • Fatty Acids Are Precursors for Phospholipids and Other Membrane Components
  • Unesterified Fatty Acids Move Within Cells Bound to Small Cytosolic Proteins
  • Incorporaton of Fatty Acids into Membrane Lipids Takes Place on Organelle Membranes
  • Flippases Move Phospholipids from One Membrane Leaflet to the Opposite Leaflet
  • 18.2 Cholesterol: A Multifunctional Membrane Lipid
  • Cholesterol Is Synthesized by Enzymes in the Cytosol and ER Membrane
  • Many Bioactive Molecules Are Made from Cholesterol and Its Biosynthetic Precursors
  • Cholesterol and Phospholipids Are Transported Between Organelles by Golgi-Independent Mechanisms
  • 18.3 Lipid Movement into and out of Cells
  • Cell-Surface Transporters Aid in Moving Fatty Acids Across the Plasma Membrane
  • ABC Proteins Mediate Cellular Export of Phospholipids and Cholesterol
  • Lipids Can Be Exported or Imported in Large Well-Defined Lipoprotein Complexes
  • Lipoproteins Are Made in the ER, Exported by the Secretory Pathway, and Remodeled in the Circulation
  • Cells Use Several Protein-Mediated Mechanisms to Import Lipoprotein Lipids
  • Analysis of Familial Hypercholesterolemie Revealed the Pathway for Receptor-Mediated Endocytosis of LDL Particles
  • Cholesteryl Esters in Lipoproteins Can Be Selectively Taken Up by the Receptor SR-BI
  • 18.4 Feedback Regulation of Cellular Lipid Metabolism
  • ER-to-Golgi Transport and Proteolytic Activation Control the Activity of SREBP Transcription Factors
  • Multiple SREBPs Regulate Expression of Numerous Lipid-Metabolizing Proteins
  • Members of the Nuclear Receptor Superfamily Contribute to Cellular and Whole-Body Lipid Regulation
  • 18.5 The Cell Biology of Atherosclerosis, Heart Attacks, and Strokes
  • Arterial Inflammation and Cellular Import of Cholesterol Mark the Early Stages of Atherosclerosis
  • Atherosclerotic Plaques Can Impede Blood Flow, Leading to Heart Attacks and Strokes
  • LDLR-Independent Uptake of LDL (Bad Cholesterol) Leads to Formation of Foam Cells
  • Reverse Cholesterol Transport by HDL (Good Cholesterol) Protects Against Atherosclerosis
  • Two Treatments for Atherosclerosis Are Based on SREBP-Regulated Cellular Cholesterol Metabolism
  • 19 Microfilaments and Intermediate Filaments
  • 19.1 Actin Structures
  • Actin Is Ancient, Abundant, and Highly Conserved
  • G-Actin Monomers Assemble into Long, Helical F-Actin Polymers
  • F-Actin Has Structural and Functional Polarity
  • CH-Domain and Other Proteins Organize Microfilaments into Bundles and Networks
  • 19.2 The Dynamics of Actin Assembly
  • Actin Polymerization in Vitro Proceeds in Three Steps
  • Actin Filaments Grow Faster at ( + ) End Than at (-) End
  • Toxins Perturb the Pool of Actin Monomers
  • Actin Polymerization Is Regulated by Proteins That Bind G-Actin
  • Filament-Binding Severing Proteins Create New Actin Ends
  • Actin-Capping Proteins Stabilize F-Actin
  • Arp2/3 Assembles Branched Filaments
  • Intracellular Movements and Changes in Cell Shape Are Driven by Actin Polymerization
  • 19.3 Myosins Powered Cell Movements
  • Myosins Are a Large Superfamily of Mechanochemical Motor Proteins
  • Myosin Heads Walk Along Actin Filaments in Discrete Steps
  • Myosin-Bound Vesicles Are Carried Along Actin Filaments
  • Actin and Myosin II Form Contractile Bundles in Nonmuscle Cells
  • Organized Thick and Thin Filaments in Skeletal Muscle Slide Past One Another During Contraction
  • Contraction of Skeletal Muscle Is Regulated by Ca2+ and Actin-Binding Proteins
  • Myosin-Dependent Mechanisms Regulate Contraction in Smooth Muscle and Nonmuscle Cells
  • 19.4 Cell Locomotion
  • Cell Movement Coordinates Force Generation with Cell Adhesion
  • Ameboid Movement Entails Reversible Gel-Sol Transitions of Actin Networks
  • External Signals and Various Signaling Pathways Coordinate Events That Lead to Cell Migration
  • 19.5 Intermediate Filaments
  • Intermediate Filaments Differ in Stability, Size, and Structure from Other Cytoskeletal Fibers
  • IF Proteins Are Classified According to Their Distributions in Specific Tissues
  • All IF Proteins Have a Conserved Core Domain and Are Organized Similarly into Filaments
  • Intermediate Filaments Are Dynamic
  • Various Proteins Cross-Link Intermediate Filaments to One Anther and to Other Cell Structures
  • IF Networks Form Various Supportive Structures and Are Connected to Cellular Membranes
  • Disruption of Keratin Networks Causes Blistering
  • 20 Microtubules
  • 20.1 Microtubule Organization and Dynamics
  • Heterodimeric Tubulin Subunits Compose the Wall of a Microtubule
  • Microtubule Assembly and Disassembly Take Place Preferentially at the (+) End
  • Dynamic Instability Is an Intrinsic Property of Microtubules
  • Numerous Proteins Regulate Microtubule Dynamics and Cross-Linkage to Other Structures
  • Colchicine and Other Drugs Disrupt Microtubule Dynamics
  • MITOCs Orient Most Microtubules and Determine Cell Polarity
  • λ-Tubulin Ring Complex Nucleates Polymerization of Tubulin Subunits
  • Cytoplasmic Organelles and Vesicles Are Organized by Microtubules
  • 20.2 Kinesin- and Dynein-Powered Movements
  • Axonal Transport Along Microtubules Is in Both Directions
  • Kinesin I Powers Anterograde Transport of Vesicles in Axons
  • Most Kinesins Are Processive (+) End Directed Motor Proteins
  • Cytosolic Dyneins Are (-) End-Directed Motor Proteins That Bind Cargo Through Dynactin
  • Multiple Motor Proteins Sometimes Move the Same Cargo
  • Eukaryotic Cilia and Flagella Contain a Core of Doublet Microtubules Studded with Axonemal Dyneins
  • Ciliary and Flagellar Beating Are Produced by Controlled Sliding of Outer Doublet Microtubules
  • 20.3 Microtubule Dynamics and Motor Proteins in Mitosis
  • Mitotic Apparatus Is a Microtubule Machine for Separating Chromosomes
  • Kinetochore Is a Centromere-Based Protein Complex That Captures and Helps Transport Chromosomes
  • Duplicated Centrosomes Align and Begin Separating in Prophase
  • Formation of the Metaphase Mitotic Spindle Requires Motor Proteins and Dynamic Microtubules
  • Anaphase Chromosomes Separate and the Spindle Elongates
  • Microtubules and Microfilaments Work Cooperatively During Cytokinesis
  • Plant Cells Reorganize Their Microtubules and Build a New Cell Wall in Mitosis
  • 21 Regulating the Eukaryotic Cell Cycle
  • 21.1 Overview of the Cell Cycle and Its Control
  • Cell Cycle Is an Ordered Series of Events Leading to Cell Replication
  • 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 --
  • Contents note continued: 21.2 Biochemical Studies with Oocytes, Eggs, and Early Embryos
  • Maturation-Promoting Factor (MPF) Stimulates Meiotic Maturation of Oocytes and Mitosis in Somatic Cells
  • Mitotic Cyclin Was First Identified in Early Sea Urchin Embryos
  • Cyclin B Levels and Kinase Activity of Mitosis Promoting Factor (MPF) Change Together in Cycling Xenopus Egg Extracts
  • Anaphase-Promoting Complex (APC) Controls Degradation of Mitotic Cyclins and Exit from Mitosis
  • 21.3 Genetic Studies with S. pombe
  • Highly Conserved MPF-like Complex Controls Entry into Mitosis in S. pombe
  • Phosphorylation of the CDK Subunit Regulates the Kinase Activity of MPF
  • Conformational Changes Induced by Cyclin Binding and Phosphorylation Increase MPF Activity
  • Other Mechanisms Also Control Entry into Mitosis by Regulating MPF Activity
  • 21.4 Molecular Mechanisms for Regulating Mitotic Events
  • Phosphorylation of Nuclear Lamins and Other Proteins Promotes Early Mitotic Events
  • Unlinking of Sister Chromatids Initiates Anaphase
  • Reassembly of the Nuclear Envelope and Cytokinesis Depend on Unopposed Constitutive Phosphatase Activity
  • 21.5 Genetic Studies with S. cerevisiae
  • Cyclin-Dependent Kinase (CDK) Is Critical for Phase Entry in S. cerevisiae
  • Three G1 Cyclins Associate with S. Cerevisiae to Form S Phase-Promoting Factors
  • Degradation of the S-Phase Inhibitor Triggers DNA Replication
  • Multiple Cyclins Direct the Kinase Activity of S. cerevisiae During Different Cell-Cycle Phases
  • Cdcl4 Phosphatase Promotes Exit from Mitosis
  • Replication at Each Origin Is Initiated Only Once During the Cell Cycle
  • 21.6 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 Phosphorylation of the Tumor-Suppressor Rb Protein
  • Cyclin A Is Required for DNA Synthesis and CDK1 for Entry into Mitosis
  • Two Types of Cyclin-CDK Inhibitors Contribute to Cell-Cycle Control in Mammals
  • 21.7 Checkpoints in Cell-Cycle Regulation
  • Presence of Unreplicated DNA Prevents Entry into Mitosis
  • Improper Assembly of the Mitotic Spindle Prevents the Initiation of Anaphase
  • Proper Segregation of Daughter Chromosomes Is Monitored by the Mitotic Exit Network
  • Cell-Cycle Arrest of Cells with Damaged DNA Depends on Tumor Suppressors
  • 21.8 Meiosis: A Special Type of Cell Division
  • Repression of G1 Cyclins and Meiosis-Specific Ime2 Prevents DNA Replication in Meiosis II
  • Crossing Over and Meiosis-Specific Rec8 Are Necessary for Specialized Chromosome Segregation in Meiosis I
  • 22 Cell Birth, Lineage, and Death
  • 22.1 The Birth of Cells
  • Stem Cells Give Rise to Stem Cells and to Differentiating Cells
  • Cultured Embryonic Stem Cells Can Differentiate into Various Cell Types
  • Tissues Are Maintained by Associated Populations of Stem Cells
  • Cell Fates Are Progressively Restricted During Development
  • Complete Cell Lineage of C. elegans Is Known
  • Heterochronic Mutants Provide Clues About Control of Cell Lineage
  • 22.2 Cell-Type Specification in Yeast
  • Transcription Factors Encoded at the MAT Locus Act in Concert with MCM1 to Specify Cell
  • MCM1 and a1-MCM1 Complexes Activate Gene Transcription
  • a2-MCM1 and a2-a1 Complexes Repress Transcription
  • Pheromones Induce Mating of a and a Cells to Generate a Third Cell Type
  • 22.3 Specification and Differentiation of Muscle
  • Embryonic Somites Give Rise to Myoblasts, the Precursors of Skeletal Muscle Cells
  • Myogenic Genes Were First Identified in Studies with Cultured Fibroblasts
  • Muscle-Regulatory Factors (MRFs) and Myocyte-Enhancing Factors (MEFs) Act in Concert to Confer Myogenic Specificity
  • Terminal Differentiation of Myoblasts Is Under Positive and Negative Control
  • Cell-Cell Signals Are Crucial for Muscle Cell-Fate Determination and Myoblast Migration
  • bHLH Regulatory Proteins Function in Creation of Other Tissues
  • 22.4 Regulation of Asymmetric Cell Division
  • Yeast Mating-Type Switching Depends upon Asymmetric Cell Division
  • Critical Asymmetry-Regulating Proteins Are Localized at Opposite Ends of Dividing Neuroblasts in Drosophila
  • Orientation of the Mitotic Spindle Is Linked to Cytoplasmic Cell-Asymmetry Factors
  • 22.5 Cell Death and Its Regulation
  • Programmed Cell Death Occurs Through Apoptosis
  • Neurotrophins Promote Survival of Neurons
  • Cascade of Caspase Proteins Functions in One Apoptotic Pathway
  • Pro-Apoptotic Regulators Permit Caspase Activation in the Absence of Trophic Factors
  • Some Trophic Factors Induce Inactivation of a Pro Apoptotic Regulator
  • Tumor Necrosis Factor and Related Death Signals Promote Cell Murder by Activating Caspases
  • 23 Cancer
  • 23.1 Tumor Cells and the Onset of Cancer
  • Metastic Tumor Cells Are Invasive and Can Spread
  • Cancers Usually Originate in Proliferating Cells
  • Tumor Growth Requires Formation of New Blood Vessels
  • Cultured Cells Can Be Transformed into Tumor Cells
  • Multi-hit Model of Cancer Induction Is Supported by Several Lines of Evidence
  • Successive Oncogenic Mutations Can Be Traced in Colon Cancers
  • 23.2 The Genetic Basis of Cancer
  • Gain of-Function Mutations Convert Proto-oncogenes into Oncogenes
  • Cancer-Causing Viruses Contain Oncogenes or Activate Cellular Proto-oncogenes
  • Loss-of-Function Mutations in Tumor-Suppressor Genes Are Oncogenic
  • Inherited Mutations in Tumor-Suppressor Genes Increase Cancer Risk
  • Aberrations in Signaling Pathways That Control Development Are Associated with Many Cancers
  • DNA Microarray Analysis of Expression Patterns Can Reveal Subtle Differences Between Tumor Cells
  • 23.3 Oncogenic Mutations in Growth-Promoting Proteins
  • Ocogenic Receptors Can Promote Proliferation in the Absence of External Growth Factors
  • Viral Activators of Growth-Factor Receptors Act as Oncoproteins
  • Many Oncogenes Encode Constitutively Active Signal Transduction Proteins
  • Inappropriate Production of Nuclear Transcription Factors Can Induce Transformation
  • 23.4 Mutations Causing Loss of Growth-Inhibiting and Cell-Cycle Controls
  • Mutations That Promote Unregulated Passage from G1 to S Phase Are Oncogenic
  • Loss-of-Function Mutations Affecting Chromatin-Remodeling Proteins Contribute to Tumors
  • Loss of p53 Abolishes the DNA-Damage Checkpoint
  • Apoptotic Genes Can Function as Proto-Oncogenes or Tumor-Suppressor Genes
  • Failure of Cell-Cycle Checkpoints Can Also Lead to Aneuploidy in Tumor Cells
  • 23.5 The Role of Carcinogens and DNA Repair in Cancer
  • DNA Polymerases Introduce Copying Errors and Also Correct Them
  • Chemical Damage to DNA Can Lead to Mutations
  • Some Carcinogens Have Been Linked to Specific Cancers
  • Loss of High-Fidelity DNA Excision-Repair Systems Can Lead to Cancer
  • Base Excision Is Used to Repair Damaged Bases and Single-Base Mispairs
  • Loss of Mismatch Excision Repair Leads to Colon and Other Cancers
  • Nucleotide Excision Repair Was Elucidated Through Study of Xeroderma Pigmentosum, a Hereditary Predisposition to Skin Cancers
  • Two Systems Repair Double-Stranded Breaks in DNA
  • Telomerase Expression Contributes to Immortalization of Cancer Cells.
Other information
  • Includes bibliographical references and index.
  • OCLC
ISBN
  • 0716743663
  • 9780716743668
Identifying numbers
  • LCCN: 2003049089
  • OCLC: 52092052
  • OCLC: 52092052

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