Book , Print in English

Molecular cell biology

Harvey Lodish [and others].
  • New York : W.H. Freeman and Co., 2013.
  • 7th ed.
  • xxxiii, 1154, [58] pages : color illustrations, portraits ; 28 cm
Subjects
Medical Subjects
Summary
  • Overview: Molecular Cell Biology presents the key concepts in cell biology and their experimental underpinnings. The authors, all world-class researchers and teachers, incorporate medically relevant examples where appropriate to help illustrate the connections between cell biology and health and human disease. As always, a hallmark of MCB is the use of experiments to engage students in the history of cell biology and the research that has contributed to the field. The book contains predominantly color illustrations, with some black-and-white illustrations.
Contents
  • note: pt. I Chemical and Molecular Foundations
  • 1. Molecules, Cells, and Evolution
  • 1.1. Molecules of Life
  • Proteins Give Cells Structure and Perform Most Cellular Tasks
  • Nucleic Acids Carry Coded Information for Making Proteins at the Right Time and Place
  • Phospholipids Are the Conserved Building Blocks of All Cellular Membranes
  • 1.2. Genomes, Cell Architecture, and Cell Function
  • Prokaryotes Comprise True Bacteria and Archaea
  • Escherichia coli Is Widely Used in Biological Research
  • All Eukaryotic Cells Have Many of the Same Organelles and Other Subcellular Structures
  • Cellular DNA Is Packaged Within Chromosomes
  • All Eukaryotic Cells Utilize a Similar Cycle to Regulate Their Division
  • 1.3. Cells into Tissues: Unicellular and Metazoan Organisms Used for Molecular Cell Biology Investigations
  • Single-Celled Eukaryotes Are Used to Study Fundamental Aspects of Eukaryotic Cell Structure and Function
  • Mutations in Yeast Led to the Identification of Key Cell
  • Cycle Proteins
  • Multicellularity Requires Cell-Cell and Cell Matrix Adhesions
  • Tissues Are Organized into Organs
  • Body Plan and Rudimentary Tissues Form Early in Embryonic Development
  • Invertebrates, Fish, and Other Organisms Serve as Experimental Systems for Study of Human Development
  • Mice Are Frequently Used to Generate Models of Human Disease
  • Viruses Are Cellular Parasites That Are Widely Employed in Molecular Cell Biology Research
  • Genetic Diseases Elucidate Important Aspects of Cell Function
  • Following Chapters Present Much Experimental Data That Explains How We Know What We Know About Cell Structure and Function
  • 2. Chemical Foundations
  • 2.1. Covalent Bonds and Noncovalent Interactions
  • Electronic Structure of an Atom Determines the Number and Geometry of Covalent Bonds It Can Make
  • Electrons May Be Shared Equally or Unequally in Covalent Bonds
  • Covalent Bonds Are Much Stronger and More Stable Than Noncovalent Interactions
  • Ionic Interactions Are Attractions Between Oppositely Charged Ions
  • Hydrogen Bonds Are Noncovalent Interactions That Determine the Water Solubility of Uncharged Molecules
  • Van der Waals Interactions Are Weak Attractive interactions Caused by Transient Dipoles
  • Hydrophobic Effect Causes Nonpolar Molecules to Adhere to One Another
  • Molecular Complementarity Due to Noncovalent Interactions Leads to a Lock-and-Key Fit Between 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 Covalently Assemble into Linear and Branched Polysaccharides
  • Phospholipids Associate Noncovalently to Form the Basic Bilayer Structure of Biomembranes
  • 2.3. Chemical Reactions and Chemical Equilibrium
  • Chemical Reaction Is in Equilibrium When the Rates of the Forward and Reverse Reactions Are Equal
  • Equilibrium Constant Reflects the Extent of a Chemical Reaction
  • Chemical Reactions in Cells Are at Steady State
  • Dissociation Constants of 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 If a Chemical Reaction Will Occur Spontaneously
  • ΔG°f of a Reaction Can Be Calculated from Its Keq
  • Rate of a Reaction Depends on the Activation Energy Necessary to Energize the Reactants into a Transition State
  • Life Depends on the Coupling of Unfavorable Chemical Reactions with Energetically Favorable Ones
  • 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
  • Tertiary Structure Is the Overall Folding of a Polypeptide Chain
  • Different Ways of Depicting the Conformation of Proteins Convey Different Types of Information
  • Structural Motifs Are Regular Combinations of Secondary Structures
  • Domains Are Modules of Tertiary Structure
  • Multiple Polypeptides Assemble into Quaternary Structures and Supramolecular Complexes
  • Members of Protein Families Have a Common Evolutionary Ancestor
  • 3.2. Protein Folding
  • Planar Peptide Bonds Limit the Shapes into Which Proteins Can Fold
  • Amino Acid Sequence of a Protein Determines How It Will Fold
  • Folding of Proteins in Vivo Is Promoted by Chaperones
  • Alternatively Folded Proteins Are Implicated in Diseases
  • 3.3. Protein Binding and Enzyme Catalysis
  • Specific Binding of Ligands Underlies the Functions of Most Proteins
  • Enzymes Are Highly Efficient and Specific Catalysts
  • Enzyme's Active Site Binds Substrates and Carries Out Catalysis
  • Serine Proteases Demonstrate How an Enzyme's Active Site Works
  • Enzymes in a Common Pathway Are Often Physically Associated with One Another
  • 3.4. Regulating Protein Function
  • Regulated Synthesis and Degradation of Proteins is a Fundamental Property of Cells
  • Proteasome Is a Molecular Machine Used to Degrade Proteins
  • Ubiquitin Marks Cytosolic Proteins for Degradation in Proteasomes
  • Noncovalent Binding Permits Allosteric, or Cooperative, Regulation of Proteins
  • Noncovalent Binding of Calcium and GTP Are Widely Used as Allosteric Switches to Control Protein Activity
  • Phosphorylation and Dephosphorylation Covalently Regulate Protein Activity
  • Ubiquitination and Deubiquitination Covalently Regulate Protein Activity
  • Proteolytic Cleavage Irreversibly Activates or Inactivates Some Proteins
  • Higher-Order Regulation Includes Control of Protein Location and Concentration
  • 3.5. 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-to-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 Can Determine the Mass and Sequence of Proteins
  • Protein Primary Structure Can Be Determined by Chemical Methods and from Gene Sequences
  • Protein Conformation Is Determined by Sophisticated Physical Methods
  • 3.6. Proteomics
  • Proteomics Is the Study of All or a Large Subset of Proteins in a Biological System
  • Advanced Techniques in Mass Spectrometry Are Critical to Proteomic Analysis
  • pt. II Genetics and Molecular Biology
  • 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
  • Torsional Stress in DNA Is Relieved by Enzymes
  • Different Types of RNA Exhibit Various Conformations 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. Decoding of mRNA by tRNAs
  • 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
  • Amino Acids Become Activated When Covalently Linked to tRNAs
  • 4.4. Stepwise Synthesis of Proteins on Ribosomes
  • Ribosomes are Protein-Synthesizing Machines
  • Methionyl-tRNAMet Recognizes the AUG Start Codon
  • Eukaryotic Translation Initiation Usually Occurs at 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
  • GTPase-Superfamily Proteins Function in Several Quality Control Steps of Translation
  • Nonsense Mutations Cause Premature Termination of Protein Synthesis
  • 4.5. DNA Replication
  • DNA Polymerases Require a Primer to Initiate Replication
  • Duplex DNA Is Unwound, and Daughter Strands Are Formed at the DNA Replication Fork
  • Several Proteins Participate in DNA Replication
  • DNA Replication Occurs Bidirectionally from Each Origin
  • 4.6. DNA Repair and Recombination
  • DNA Polymerases Introduce Copying Errors and Also Correct Them
  • Chemical and Radiation Damage to DNA Can Lead to Mutations
  • High-Fidelity DNA Excision Repair Systems Recognize and Repair Damage
  • Base Excision Repairs T-G Mismatches and Damaged Bases
  • Mismatch Excision Repairs Other Mismatches and Small Insertions and Deletions
  • Nucleotide Excision Repairs Chemical Adducts that Distort Normal DNA Shape
  • Two Systems Utilize Recombination to Repair Double-Strand Breaks in DNA --
  • Contents note continued: Homologous Recombination Can Repair DNA Damage and Generate Genetic Diversity
  • 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
  • Lytic Viral Growth Cycles Lead to Death of Host Cells
  • Viral DNA Is Integrated into the Host-Cell Genome in Some Nonlytic Viral Growth Cycles
  • 5. Molecular Genetic Techniques
  • 5.1. 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
  • Genes Can Be Identified by Their Map Position on the Chromosome
  • 5.2. DNA Cloning and Characterization
  • Restriction Enzymes and DNA Ligases Allow Insertion of DNA Fragments into Cloning Vectors
  • E. coli Plasmid Vectors Are Suitable for Cloning isolated DNA Fragments
  • cDNA Libraries Represent the Sequences of Protein-Coding Genes
  • 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
  • Yeast Genomic Libraries Can Be Constructed with Shuttle Vectors and Screened by Functional Complementation
  • Gel Electrophoresis Allows Separation of Vector DNA from Cloned Fragments
  • Polymerase Chain Reaction Amplifies a Specific DNA Sequence from a Complex Mixture
  • Cloned DNA Molecules Are Sequenced Rapidly by Methods Based on PCR
  • 5.3. Using Cloned DNA Fragments to Study Gene Expression
  • Hybridization Techniques Permit Detection of Specific DNA Fragments and mRNAs
  • 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
  • E. coli Expression Systems Can Produce Large Quantities of Proteins from Cloned Genes
  • Plasmid Expression Vectors Can Be Designed for Use in Animal Cells
  • 5.4. Locating and Identifying Human Disease Genes
  • Monogenic Diseases Show One of Three Patterns of Inheritance
  • DNA Polymorphisms Are Used as Markers for Linkage-Mapping of Human Mutations
  • Linkage Studies Can Map Disease Genes with a Resolution of About 1 Centimorgan
  • Further Analysis is Needed to Locate a Disease Gene in Cloned DNA
  • Many Inherited Diseases Result from Multiple Genetic Defects
  • 5.5. 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
  • RNA Interference Causes Gene Inactivation by Destroying the Corresponding mRNA
  • 6. Genes, Genomics, and Chromosomes
  • 6.1. Eukaryotic Gene Structure
  • Most Eukaryotic Genes Contain Introns and Produce mRNAs Encoding Single Proteins
  • Simple and Complex Transcription Units Are Found in Eukaryotic Genomes
  • Protein-Coding Genes May Be Solitary or Belong to a Gene Family
  • Heavily Used Gene Products Are Encoded by Multiple Copies of Genes
  • Nonprotein-Coding Genes Encode Functional RNAs
  • 6.2. Chromosomal Organization of Genes and Noncoding DNA
  • Genomes of Many Organisms Contain Nonfunctional DNA
  • Most Simple-Sequence DNAs Are Concentrated in Specific Chromosomal Locations
  • DNA Fingerprinting Depends on Differences in Length of Simple-Sequence DNAs
  • Unclassified Spacer DNA Occupies a Significant Portion of the Genome
  • 6.3. Transposable (Mobile) DNA Elements
  • Movement of Mobile Elements Involves a DNA or an RNA Intermediate
  • DNA Transposons Are Present in Prokaryotes and Eukaryotes
  • LTR Retrotransposons Behave Like Intracellular Retroviruses
  • Non-LTR Retrotransposons Transpose by a Distinct Mechanism
  • Other Retroposed RNAs Are Found in Genomic DNA
  • Mobile DNA Elements Have Significantly Influenced Evolution
  • 6.4. Organelle DNAs
  • Mitochondria Contain Multiple mtDNA Molecules
  • mtDNA Is Inherited Cytoplasmically
  • Size, Structure, and Coding Capacity of mtDNA Vary Considerably Between Organisms
  • Products of Mitochondria! Genes Are Not Exported
  • Mitochondria Evolved from a Single Endosymbiotic Event Involving a Rickettsia-like Bacterium
  • Mitochondrial Genetic Codes Differ from the Standard Nuclear Code
  • Mutations in Mitochondrial DNA Cause Several Genetic Diseases in Humans
  • Chloroplasts Contain Large DNAs Often Encoding More Than a Hundred Proteins
  • 6.5. 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
  • Number of Protein-Coding Genes in an Organism's Genome Is Not Directly Related to Its Biological Complexity
  • 6.6. Structural Organization of Eukaryotic Chromosomes
  • Chromatin Exists in Extended and Condensed Forms
  • Modifications of Histone Tails Control Chromatin Condensation and Function
  • Nonhistone Proteins Organize Long Chromatin Loops
  • Additional Nonhistone Proteins Regulate Transcription and Replication
  • 6.7. 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
  • Chromosome Painting and DNA Sequencing Reveal the Evolution of Chromosomes
  • Interphase Polytene Chromosomes Arise by DNA Amplification
  • Three Functional Elements Are Required for Replication and Stable Inheritance of Chromosomes
  • Centromere Sequences Vary Greatly in Length and Complexity
  • Addition of Telomeric Sequences by Telomerase Prevents Shortening of Chromosomes
  • 7. Transcriptional Control of Gene Expression
  • 7.1. Control of Gene Expression in Bacteria
  • Transcription Initiation by Bacterial RNA Polymerase Requires Association with a Sigma Factor
  • Initiation of lac Operon Transcription Can Be Repressed and Activated
  • Small Molecules Regulate Expression of Many Bacterial Genes via DNA-Binding Repressors and Activators
  • Transcription Initiation from' Some Promoters Requires Alternative Sigma Factors
  • Transcription by σ54-RNA Polymerase Is Controlled by Activators That Bind Far from the Promoter
  • Many Bacterial Responses Are Controlled by Two-Component Regulatory Systems
  • Control of Transcription Elongation
  • 7.2. Overview of Eukaryotic Gene Control
  • Regulatory Elements in Eukaryotic DNA Are Found Both Close to and Many Kilobases Away from Transcription Start Sites
  • Three Eukaryotic RNA Polymerases Catalyze Formation of Different RNAs
  • Largest Subunit in RNA Polymerase II Has an Essential Carboxyl-Terminal Repeat
  • 7.3. RNA Polymerase II Promoters and General Transcription Factors
  • RNA Polymerase II Initiates Transcription at DNA Sequences Corresponding to the 5' Cap of mRNAs
  • TATA Box, Initiators, and CpG Islands Function as Promoters in Eukaryotic DNA
  • General Transcription Factors Position RNA Polymerase II at Start Sites and Assist in Initiation
  • In Vivo Transcription Initiation by RNA Polymerase II Requires Additional Proteins
  • Elongation Factors Regulate the Initial Stages of Transcription in the Promoter-Proximal Region
  • 7.4. Regulatory Sequences in Protein-Coding Genes and the Proteins Through Which They Function
  • 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
  • Footprinting and Gel-Shift Assays Detect Protein-DNA Interactions
  • Activators Promote Transcription and Are Composed of Distinct Functional Domains
  • Repressors Inhibit Transcription and Are the Functional Converse of Activators
  • DNA-Binding Domains Can Be Classified into Numerous Structural Types
  • Structurally Diverse Activation and Repression Domains Regulate Transcription
  • Transcription Factor Interactions Increase Gene-Control Options
  • Multiprotein Complexes Form on Enhancers
  • 7.5. Molecular Mechanisms of Transcription Repression and Activation
  • 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
  • Chromatin-Remodeling Factors Help Activate or Repress Transcription
  • Mediator Complex Forms a Molecular Bridge Between Activation Domains and Pol II
  • Yeast Two-Hybrid System
  • 7.6. Regulation of Transcription-Factor Activity
  • All Nuclear Receptors Share a Common Domain Structure
  • Nuclear-Receptor Response Elements Contain inverted or Direct Repeats
  • Hormone Binding to a Nuclear Receptor Regulates Its Activity as a Transcription Factor --
  • Contents note continued: Metazoans Regulate the Pol II Transition from Initiation to Elongation
  • Pol II Termination Is Also Regulated
  • 7.7. Epigenetic Regulation of Transcription
  • Epigenetic Repression by DNA Methylation
  • Histone Methylation at Other Specific Lysines Are Linked to Epigenetic Mechanisms of Gene Repression
  • Epigenetic Control by Polycomb and Trithorax Complexes
  • Noncoding RNAs Direct Epigenetic Repression in Metazoans
  • Plants and Fission Yeast Use Short RNA-Directed Methylation of Histones and DNA
  • 7.8. 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
  • 8. Post-transcriptional Gene Control
  • 8.1. Processing of Eukaryotic Pre-mRNA
  • 5' Cap Is Added to Nascent RNAs Shortly After Transcription Initiation
  • Diverse Set of Proteins with Conserved RNA-Binding Domains Associate with Pre-mRNAs
  • Splicing Occurs at Short, Conserved Sequences in Pre-mRNAs via Two Transesterification Reactions
  • During Splicing, snRNAs Base-Pair with Pre-mRNA
  • Spliceosomes, Assembled from snRNPs and a Pre-mRNA, 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
  • 3' Cleavage and Polyadenylation of Pre-mRNAs Are Tightly Coupled
  • Nuclear Exonucleases Degrade RNA That Is Processed Out of Pre-mRNAs
  • 8.2. Regulation of Pre-mRNA Processing
  • Alternative Splicing Generates Transcripts with Different Combinations of Exons
  • Cascade of Regulated RNA Splicing Controls Drosophila Sexual Differentiation
  • Splicing Repressors and Activators Control Splicing at Alternative Sites
  • RNA Editing Alters the Sequences of Some Pre-mRNAs
  • 8.3. Transport of mRNA Across the Nuclear Envelope
  • Macromolecules Exit and Enter the Nucleus Through Nuclear Pore Complexes
  • Pre-mRNAs in Spliceosomes Are Not Exported from the Nucleus
  • HIV Rev Protein Regulates the Transport of Unspliced Viral mRNAs
  • 8.4. Cytoplasmic Mechanisms of Post-transcriptional Control
  • Micro RNAs Repress Translation of Specific mRNAs
  • RNA Interference Induces Degradation of Precisely Complementary mRNAs
  • Cytoplasmic Polyadenylation Promotes Translation of Some mRNAs
  • Degradation of mRNAs in the Cytoplasm Occurs by Several Mechanisms
  • Protein Synthesis Can Be Globally Regulated
  • Sequence-Specific RNA-Binding Proteins Control Specific mRNA Translation
  • Surveillance Mechanisms Prevent Translation of Improperly Processed mRNAs
  • Localization of mRNAs Permits Production of Proteins at Specific Regions Within the Cytoplasm
  • 8.5. Processing of rRNA and tRNA
  • Pre-rRNA Genes Function as Nucleolar Organizers and Are Similar in All Eukaryotes
  • Small Nucleolar RNAs Assist in Processing Pre-rRNAs
  • Self-Splicing Group I Introns Were the First Examples of Catalytic RNA
  • Pre-tRNAs Undergo Extensive Modification in the Nucleus
  • Nuclear Bodies Are Functionally Specialized Nuclear Domains
  • pt. III Cell Structure and Function
  • 9. Culturing, Visualizing, and Perturbing Cells
  • 9.1. Growing Cells in Culture
  • 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
  • Flow Cytometry Separates Different Cell Types
  • Growth of Cells in Two-Dimensional and Three-Dimensional Culture Mimics the In Vivo Environment
  • Hybrid Cells Called Hybridomas Produce Abundant Monoclonal Antibodies
  • 9.2. Light Microscopy: Exploring Cell Structure and Visualizing Proteins Within Cells
  • Resolution of the Light Microscope Is About 0.2 μm
  • Phase-Contrast and Differential-Interference-Contrast Microscopy Visualize Unstained Living Cells
  • Imaging Subcellular Details Often Requires That the Samples Be Fixed, Sectioned, and Stained
  • Fluorescence Microscopy Can Localize and Quantify Specific Molecules in Live Cells
  • Determination of Intracellular Ca2+ and H+ Levels with Ion-Sensitive Fluorescent Dyes
  • Immunofluorescence Microscopy Can Detect Specific Proteins in Fixed Cells
  • Tagging with Fluorescent Proteins Allows the Visualization of Specific Proteins in Living Cells
  • Deconvolution and Confocal Microscopy Enhance Visualization of Three-Dimensional Fluorescent Objects
  • TIRF Microscopy Provides Exceptional Imaging in One Focal Plane
  • FRAP Reveals the Dynamics of Cellular Components
  • FRET Measures Distance Between Chromophores
  • Super-Resolution Microscopy Can Localize Proteins to Nanometer Accuracy
  • 9.3. Electron Microscopy: High-Resolution Imaging
  • Single Molecules or Structures Can Be Imaged After a Negative Stain or Metal Shadowing
  • Cells and Tissues Are Cut into Thin Sections for Viewing by Electron Microscopy
  • Immunoelectron Microscopy Localizes Proteins at the Ultrastructural Level
  • Cryoelectron Microscopy Allows Visualization of Specimens Without Fixation or Staining
  • Scanning Electron Microscopy of Metal-Coated Specimens Reveals Surface Features
  • 9.4. Isolation and Characterization of Cell Organelles
  • Organelles of the Eukaryotic Cell
  • 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
  • Proteomics Reveals the Protein Composition of Organelles
  • 9.5. Perturbing Specific Cell Functions
  • Drugs Are Commonly Used in Cell Biology
  • Chemical Screens Can Identify New Specific Drugs
  • Small Interfering RNAs (siRNAs} Can Knock Down Expression of Specific Proteins
  • Genomic Screens Using siRNA in the Nematode C. elegans
  • Classic Experiment 9.1 Separating Organelles
  • 10. Biomembrane Structure
  • 10.1. Lipid Bilayer: Composition and Structural Organization
  • Phospholipids Spontaneously Form Bilayers
  • Phospholipid Bilayers Form a Sealed Compartment Surrounding an Internal Aqueous Space
  • Biomembranes Contain Three Principal Classes of Lipids
  • Most Lipids and Many Proteins Are Laterally Mobile in Biomembranes
  • Lipid Composition Influences the Physical Properties of Membranes
  • Lipid Composition Is Different in the Exoplasmic and Cytosolic Leaflets
  • Cholesterol and Sphingolipids Cluster with Specific Proteins in Membrane Microdomains
  • Cells Store Excess Lipids in Lipid Droplets
  • 10.2. Membrane Proteins: Structure and Basic Functions
  • Proteins Interact with Membranes in Three Different Ways
  • Most Transmembrane Proteins Have Membrane-Spanning α Helices
  • Multiple β Strands in Porins Form Membrane-Spanning "Barrels"
  • Covalently Attached Lipids Anchor Some Proteins to Membranes
  • All Transmembrane Proteins and Glycolipids Are Asymmetrically Oriented in the Bilayer
  • Lipid-Binding Motifs Help Target Peripheral Proteins to the Membrane
  • Proteins Can Be Removed from Membranes by Detergents or High-Salt Solutions
  • 10.3. Phospholipids, Sphingolipids, and Cholesterol: Synthesis and Intracellular Movement
  • Fatty Acids Are Assembled from Two-Carbon Building Blocks by Several Important Enzymes
  • Small Cytosolic Proteins Facilitate Movement of Fatty Acids
  • Fatty Acids Are Incorporated into Phospholipids Primarily on the ER Membrane
  • Flippases Move Phospholipids from One Membrane Leaflet to the Opposite Leaflet
  • Cholesterol Is Synthesized by Enzymes in the Cytpsol and ER Membrane
  • Cholesterol and Phospholipids Are Transported Between Organelles by Several Mechanisms
  • 11. Transmembrane Transport of Ions and Small Molecules
  • 11.1. Overview of Transmembrane Transport
  • Only Gases and Small Uncharged Molecules Cross Membranes by Simple Diffusion
  • Three Main Classes of Membrane Proteins Transport Molecules and Ions Across Biomembranes
  • 11.2. Facilitated Transport of Glucose and Water
  • Uniport Transport Is Faster and More Specific than Simple Diffusion
  • Low Km of the GLUT1 Uniporter Enables It to Transport Glucose into Most Mammalian Cells
  • Human Genome Encodes a Family of Sugar-Transporting GLUT Proteins
  • Transport Proteins Can Be Studied Using Artificial Membranes and Recombinant Cells
  • Osmotic Pressure Causes Water to Move Across Membranes
  • Aquaporins Increase the Water Permeability of Cell Membranes
  • 11.3. ATP-Powered Pumps and the intracellular Ionic Environment
  • There are Four Main Classes of ATP-Powered Pumps
  • ATP-Powered Ion Pumps Generate and Maintain Ionic Gradients Across Cellular Membranes
  • Muscle Relaxation Depends on Ca2+ ATPases That Pump Ca2+ from the Cytosol into the Sarcoplasmic Reticulum
  • Mechanism of Action of the Ca2+ Pump Is Known in Detail
  • Calmodulin Regulates the Plasma Membrane Pumps That Control Cytosolic Ca2+ Concentrations
  • Na+/K+ ATPase Maintains the Intracellular Na+ and K+ Concentrations in Animal Cells
  • V-Class H+ ATPases Maintain the Acidity of Lysosomes and Vacuoles
  • ABC Proteins Export a Wide Variety of Drugs and Toxins from the Cell
  • Certain ABC Proteins "Flip" Phospholipids and Other Lipid-Soluble Substrates from One Membrane Leaflet to the Other
  • ABC Cystic Fibrosis Transmembrane Regulator (CFTR) Is a Chloride Channel, Not a Pump
  • 11.4. Nongated Ion Channels and the Resting Membrane Potential
  • Selective Movement of Ions Creates a Transmembrane Electric Gradient
  • Resting Membrane Potential in Animal Cells Depends Largely on the Outward Flow of K+ Ions Through Open K+ Channels --
  • Contents note continued: Ion Channels Are Selective for Certain Ions by Virtue of a Molecular "Selectivity Filter"
  • 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
  • 11.5. Cotransport by Symporters and Antiporters
  • Na+ Entry into Mammalian Cells Is Thermodynamically Favored
  • Na+-Linked Symporters Enable Animal Cells to Import Glucose and Amino Acids Against High Concentration Gradients
  • Bacterial Na+/Amino Acid Symporter Reveals How Symport Works
  • Na+-Linked Ca2+ Antiporter Regulates the Strength of Cardiac Muscle Contraction
  • Several Cotransporters Regulate Cytosolic ph
  • Anion Antiporter Is Essential for Transport of CO2 by Red Blood Cells
  • Numerous Transport Proteins Enable Plant Vacuoles to Accumulate Metabolites and Ions
  • 11.6. Transcellular Transport
  • Multiple Transport Proteins Are Needed to Move Glucose and Amino Acids Across Epithelia
  • 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
  • Bone Resprption Requires Coordinated Function of a V-Class Proton Pump and a Specific Chloride Channel Protein
  • Classic Experiment 11.1 Stumbling upon Active Transport
  • 12. Cellular Energetics
  • 12.1. First Step of Harvesting Energy from Glucose: Glycolysis
  • During Glycolysis (Stage I), Cytosolic Enzymes Convert Glucose to Pyruvate
  • Rate of Glycolysis Is Adjusted to Meet the Cell's Need for ATP
  • Glucose Is Fermented When Oxygen Is Scarce
  • 12.2. Mitochondria and the Citric Acid Cycle
  • Mitochondria Are Dynamic Organelles with Two Structurally and Functionally Distinct Membranes
  • In the First Part of Stage II, Pyruvate Is Converted to Acetyl CoA and High-Energy Electrons
  • In the Second Part of Stage II, the Citric Acid Cycle Oxidizes the Acetyl Group in Acetyl CoA to CO2 and Generates High-Energy Electrons
  • Transporters in the Inner Mitochondrial Membrane Help Maintain Appropriate Cytosolic and Matrix Concentrations of NAD+ and NADH
  • Mitochondrial Oxidation of Fatty Acids Generates ATP
  • Peroxisomal Oxidation of Fatty Acids Generates No ATP
  • 12.3. Electron Transport Chain and Generation of the Proton-Motive Force
  • Oxidation of NADH and FADH2 Releases a Significant Amount of Energy
  • Electron Transport in Mitochondria Is Coupled to Proton Pumping
  • Electrons Flow "Downhill" Through a Series of Electron Carriers
  • Four Large Multiprotein Complexes Couple Electron Transport to Proton Pumping Across the Mitochondria! Inner Membrane
  • Reduction Potentials of Electron Carriers in the Electron Transport Chain Favor Electron Flow from NADH to O2
  • Multiprotein Complexes of the Electron Transport Chain Assemble into Supercomplexes
  • Reactive Oxygen Species (ROS) Are Toxic By-products of Electron Transport That Can Damage Cells
  • Experiments Using Purified Electron Transport Chain Complexes Established the Stoichiometry of Proton Pumping
  • Proton-Motive Force in Mitochondria Is Due Largely to a Voltage Gradient Across the Inner Membrane
  • 12.4. Harnessing the Proton-Motive Force to Synthesize ATP
  • Mechanism of ATP Synthesis Is Shared Among Bacteria, Mitochondria, and Chloroplasts
  • ATP Synthase Comprises F0 and F1 Multiprotein Complexes
  • Rotation of the F1 γ Subunit, Driven by Proton Movement Through F0, Powers ATP Synthesis
  • Multiple Protons Must Pass Through ATP Synthase to Synthesize One ATP
  • F0 C Ring Rotation Is Driven by Protons Flowing Through Transmembrane Channels
  • ATP-ADP Exchange Across the Inner Mitochondrial Membrane Is Powered by the Proton-Motive Force
  • Rate of Mitochondria! Oxidation Normally Depends on ADP Levels
  • Brown-Fat Mitochondria Use the Proton-Motive Force to Generate Heat
  • 12.5. Photosynthesis and Light-Absorbing Pigments
  • Thylakoid Membranes in Chloroplasts 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
  • Internal Antenna and Light-Harvesting Complexes Increase the Efficiency of Photosynthesis
  • 12.6. Molecular Analysis of Photosystems
  • Single Photosystem of Purple Bacteria Generates a Proton-Motive Force but No O2
  • 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
  • Multiple Mechanisms Protect Cells Against Damage from Reactive Oxygen Species During Photoelectron Transport
  • Cyclic Electron Flow Through PSI Generates a Proton-Motive Force but No NADPH or O2
  • Relative Activities of Photosystems I and II Are Regulated
  • 12.7. CO2 Metabolism During Photosynthesis
  • Rubisco Fixes CO2 in the Chloroplast Stroma
  • Synthesis of Sucrose Using Fixed CO2 Is Completed in the Cytosol
  • Light and Rubisco Activase Stimulate CO2 Fixation
  • Photorespiration Competes with Carbon Fixation and Is Reduced in C4 Plants
  • 13. Moving Proteins into Membranes and Organelles
  • 13.1. Targeting Proteins to and Across the ER Membrane
  • Pulse-Labeling Experiments with Purified ER Membranes Demonstrated That Secreted Proteins Cross 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 Translation
  • ATP Hydrolysis Powers Post-translational Translocation of Some Secretory Proteins in Yeast
  • 13.2. Insertion of Membrane Proteins into the ER
  • 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
  • 13.3. 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
  • 13.4. Targeting of Proteins to Mitochondria 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 Cytoplasmic Membrane
  • 13.5. Targeting of Peroxisomal Proteins
  • Cytosolic Receptor Targets Proteins with an SKL Sequence at the C-Terminus into the Peroxisomal Matrix
  • Peroxisomal Membrane and Matrix Proteins Are Incorporated by Different Pathways
  • 13.6. Transport into and out of the Nucleus
  • Large and Small Molecules Enter and Leave the Nucleus via Nuclear Pore Complexes
  • Nuclear Transport Receptors Escort Proteins Containing Nuclear-Localization Signals into the Nucleus
  • Second Type of Nuclear Transport Receptors Escort Proteins Containing Nuclear-Export Signals out of the Nucleus
  • Most mRNAs Are Exported from the Nucleus by a Ran-Independent Mechanism
  • 14. Vesicular Traffic, Secretion, and Endocytosis
  • 14.1. 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
  • 14.2. Molecular Mechanisms of Vesicle Budding and Fusion
  • 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
  • 14.3. 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 Maturation
  • 14.4. Later Stages of the Secretory Pathway
  • Vesicles Coated with Clathrin and/or Adapter Proteins Mediate Transport from the trans-Golgi --
  • Contents note continued: 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
  • 14.5. Receptor-Mediated Endocytosis
  • Cells Take Up Lipids from the Blood in the Form of Large, Well-Defined Lipoprotein Complexes
  • 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 the Receptor-Transferrin Complex in Endosomes
  • 14.6. Directing Membrane Proteins and Cytosolic Materials to the Lysosome
  • Multivesicular Endosomes Segregate Membrane Proteins Destined for the Lysosomal Membrane from Proteins Destined for Lysosomal Degradation
  • Retroviruses Bud from the Plasma Membrane by a Process Similar to Formation of Multivesicular Endosomes
  • Autophagic Pathway Delivers Cytosolic Proteins or Entire Organelles to Lysosomes
  • Classic Experiment 14.1 Following a Protein Out of the Cell
  • 15. Signal Transduction and G Protein-Coupled Receptors
  • 15.1. Signal Transduction: From Extracellular Signal to Cellular Response
  • Signaling Molecules Can Act Locally or at a Distance
  • Binding of Signaling Molecules Activates Receptors on Target Cells
  • Protein Kinases and Phosphatases Are Employed in Virtually All Signaling Pathways
  • GTP-Binding Proteins Are Frequently Used in Signal Transduction as On/Off Switches
  • Intracellular "Second Messengers" Transmit and Amplify Signals from Many Receptors
  • 15.2. Studying Cell-Surface Receptors and Signal Transduction Proteins
  • Dissociation Constant Is a Measure of the Affinity of a Receptor for Its Ligand
  • Binding Assays Are Used to Detect Receptors and Determine Their Affinity and Specificity for Ligands
  • Maximal Cellular Response to a Signaling Molecule Usually Does Not Require Activation of All Receptors
  • Sensitivity of a Cell to External Signals Is Determined by the Number of Surface Receptors and Their Affinity for Ligand
  • Receptors Can Be Purified by Affinity Techniques
  • Immunoprecipitation Assays and Affinity Techniques Can Be Used to Study the Activity of Signal Transduction Proteins
  • 15.3. G Protein-Coupled Receptors: Structure and Mechanism
  • All G Protein-Coupled Receptors Share the Same Basic Structure
  • Ligand-Activated G Protein-Coupled Receptors Catalyze Exchange of GTP for GDP on the a Subunit of α Trimeric G Protein
  • Different G Proteins Are Activated by Different GPCRs and In Turn Regulate Different Effector Proteins
  • 15.4. G Protein-Coupled Receptors That Regulate Ion Channels
  • Acetylcholine Receptors in the Heart Muscle Activate a G Protein That Opens K+ Channels
  • Light Activates G Protein-Coupled Rhodopsins in Rod Cells of the Eye
  • Activation of Rhodopsin by Light Leads to Closing of cGMP-Gated Cation Channels
  • Signal Amplification Makes the Rhodopsin Signal Transduction Pathway Exquisitely Sensitive
  • Rapid Termination of the Rhodopsin Signal Transduction Pathway Is Essential for Acute Vision
  • Rod Cells Adapt to Varying Levels of Ambient Light by Intracellular Trafficking of Arrestin and Transducin
  • 15.5. G Protein-Coupled Receptors That Activate or Inhibit Adenylyl Cyclase
  • Adenylyl Cyclase Is Stimulated and Inhibited by Different Receptor-Ligand Complexes
  • Structural Studies Established How Gαs · GTP Binds to and Activates Adenylyl Cyclase
  • cAMP Activates Protein Kinase A by Releasing Inhibitory Subunits
  • Glycogen Metabolism Is Regulated by Hormone-Induced Activation of Protein Kinase A
  • cAMP-Mediated Activation of Protein Kinase A Produces Diverse Responses in Different Cell Types
  • Signal Amplification Occurs in the cAMP-Protein Kinase A Pathway
  • CREB Links cAMP and Protein Kinase A to Activation of Gene Transcription
  • Anchoring Proteins Localize Effects of cAMP to Specific Regions of the Cell
  • Multiple Mechanisms Down-Regulate Signaling from the GPCR/cAMP/PKA Pathway
  • 15.6. G Protein-Coupled Receptors That Trigger Elevations in Cytosolic Ca2+
  • Activated Phospholipase C Generates Two Key Second Messengers Derived from the Membrane Lipid Phosphatidylinositol
  • Ca2+-Calmodulin Complex Mediates Many Cellular Responses to External Signals
  • Signal-Induced Relaxation of Vascular Smooth Muscle Is Mediated by a Ca2+-Nitric Oxide-cGMP-Activated Protein Kinase G Pathway
  • Integration of Ca2+ and cAMP Second Messengers Regulates Glycogenolysis
  • Classic Experiment 15.1 Infancy of Signal Transduction---GTP Stimulation of cAMP Synthesis
  • 16. Signaling Pathways That Control Gene Expression
  • 16.1. Receptors That Activate Protein Tyrosine Kinases
  • Numerous Factors Regulating Cell Division and Metabolism Are Ligands for Receptor Tyrosine Kinases
  • Binding of Ligand Promotes Dimerization of an RTK and Leads to Activation of Its Intrinsic Kinase
  • Homo- and Hetero-oligomers of Epidermal Growth Factor Receptors Bind Members of the Epidermal Growth Factor Superfamily
  • Cytokines Influence Development of Many Cell Types
  • Binding of a Cytokine to Its Receptor Activates a Tightly Bound JAK Protein Tyrosine Kinase
  • Phosphotyrosine Residues Are Binding Surfaces for Multiple Proteins with Conserved Domains
  • SH2 Domains in Action: JAK Kinases Activate STAT Transcription Factors
  • Multiple Mechanisms Down-Regulate Signaling from RTKs and Cytokine Receptors
  • 16.2. Ras/MAP Kinase Pathway
  • Ras, a GTPase Switch Protein, Operates Downstream of Most RTKs and Cytokine Receptors
  • Genetic Studies in Drosophila Identified Key Signal-Transducing Proteins in the Ras/MAP Kinase Pathway
  • Receptor Tyrosine Kinases and JAK Kinases Are Linked to Ras by Adapter Proteins
  • Binding of Sos to Inactive Ras Causes a Conformational Change That Triggers an Exchange of GTP for GDP
  • Signals Pass from Activated Ras to a Cascade of Protein Kinases, Ending with MAP Kinase
  • Phosphorylation of MAP Kinase Results in a Conformational Change That Enhances Its Catalytic Activity and Promotes Kinase Dimerization
  • 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 Separate Multiple MAP Kinase Pathways in Eukaryotic Cells
  • 16.3. Phosphoinositide Signaling Pathways
  • Phospholipase Cγ Is Activated by Some RTKs and Cytokine Receptors
  • Recruitment of PI-3 Kinase to Activated Receptors Leads to Synthesis of Three Phosphorylated Phosphatidylinositols
  • Accumulation of PI-3-Phosphates in the Plasma Membrane Leads to Activation of Several Kinases
  • Activated Protein Kinase B Induces Many Cellular Responses
  • PI-3 Kinase Pathway Is Negatively Regulated by PTEN Phosphatase
  • 16.4. Receptor Serine Kinases That Activate Smads
  • Three Separate TGF-Bβ Receptor Proteins Participate in Binding TGF-β and Activating Signal Transductron
  • Activated TGF-β Receptors Phosphorylate Smad Transcription Factors
  • Negative Feedback Loops Regulate TGF-β/Smad Signaling
  • 16.5. Signaling Pathways Controlled by Ubiquitination: Wnt, Hedgehog
  • And NF-κB
  • Wnt Signaling Triggers Release of a Transcription Factor from a Cytosolic Protein Complex
  • Hedgehog Signaling Relieves Repression of Target Genes
  • Hedgehog Signaling in Vertebrates Involves Primary Cilia
  • Degradation of an Inhibitor Protein Activates the NF-κB Transcription Factor
  • Polyubiquitin Chains Serve as Scaffolds Linking Receptors to Downstream Proteins in the NF-κB Pathway
  • 16.6. Signaling Pathways Controlled by Protein Cleavage: Notch/Delta, SREBP
  • On Binding Delta, the Notch Receptor Is Cleaved, Releasing a Component Transcription Factor
  • Matrix Metalloproteases Catalyze Cleavage of Many Signaling Proteins from the Cell Surface
  • Inappropriate Cleavage of Amyloid Precursor Protein Can Lead to Alzheimer's Disease
  • Regulated Intramembrane Proteolysis of SREBP Releases a Transcription Factor That Acts to Maintain Phospholipid and Cholesterol Levels
  • 16.7. Integration of Cellular Responses to Multiple Signaling Pathways
  • Insulin and Glucagon Work Together to Maintain a Stable Blood Glucose Level
  • Multiple Signal Transduction Pathways Interact to Regulate Adipocyte Differentiation Through PPARγ, the Master Transcriptional Regulator
  • 17. Cell Organization and Movement I: Microfilaments
  • 17.1. Microfilaments and 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
  • 17.2. Dynamics of Actin Filaments
  • Actin Polymerization in Vitro Proceeds in Three Steps
  • Actin Filaments Grow Faster at (+) Ends Than at (-) Ends
  • Actin Filament Treadmilling Is Accelerated by Profilin and Cofilin
  • Thymosin-β4 Provides a Reservoir of Actin for Polymerization
  • Capping Proteins Block Assembly and Disassembly at Actin Filament Ends
  • 17.3. Mechanisms of Actin Filament Assembly
  • Formins Assemble Unbranched Filaments
  • Arp2/3 Complex Nucleates Branched Filament Assembly
  • Intracellular Movements Can Be Powered by Actin Polymerization
  • Microfilaments Function in Endocytosis --
  • Contents note continued: Toxins That Perturb the Pool of Actin Monomers Are Useful for Studying Actin Dynamics
  • 17.4. Organization of Actin-Based Cellular Structures
  • Cross-Linking Proteins Organize Actin Filaments into Bundles or Networks
  • Adaptor Proteins Link Actin Filaments to Membranes
  • 17.5. Myosins: Actin-Based Motor Proteins
  • Myosins Have Head, Neck, and Tail Domains with Distinct Functions
  • Myosins Make Up a Large Family of Mechanochemical Motor Proteins
  • Conformational Changes in the Myosin Head Couple ATP Hydrolysis to Movement
  • Myosin Heads Take Discrete Steps Along Actin Filaments
  • Myosin V Walks Hand over Hand down an Actin Filament
  • 17.6. Myosin-Powered Movements
  • Myosin Thick Filaments and Actin Thin Filaments in Skeletal Muscle Slide Past One Another During Contraction
  • Skeletal Muscle is Structured by Stabilizing and Scaffolding Proteins
  • Contraction of Skeletal Muscle Is Regulated by Ca2+ and Actin-Binding Proteins
  • Actin and Myosin II Form Contractile Bundles in Nonmuscle Cells
  • Myosin-Dependent Mechanisms Regulate Contraction in Smooth Muscle and Nonmuscle Cells
  • Myosin-V-Bound Vesicles Are Carried Along Actin Filaments
  • Migration; Mechanism, Signaling, and Chemotaxis
  • Cell Migration Coordinates Force Generation with Cell Adhesion and Membrane Recycling
  • Small GTP-Binding Proteins Cdc42, Rac, and Rho Control Actin Organization
  • Cell Migration Involves the Coordinate Regulation of Cdc42, Rac, and Rho
  • Migrating Cells Are Steered by Chemotactic Molecules
  • Chemotactic Gradients Induce Altered Phosphoinositide Levels Between the Front and Back of a Cell
  • Classic Experiment 17.1 Looking at Muscle Contraction
  • 18. Cell Organization and Movement II: Microtubules and Intermediate Filaments
  • 18.1. Microtubule Structure and Organization
  • Microtubule Walls Are Polarized Structures Built from αβ-Tubulin Dimers
  • Microtubules Are Assembled from MTOCs to Generate Diverse Organizations
  • 18.2. Microtubule Dynamics
  • Individual Microtubules Exhibit Dynamic Instability
  • Localized Assembly and "Search-and-Capture" Help Organize Microtubules
  • Drugs Affecting Tubulin Polymerization Are Useful Experimentally and in Treatment of Diseases
  • 18.3. Regulation of Microtubule Structure and Dynamics
  • Microtubules Are Stabilized by Side-Binding Proteins
  • +TIPs Regulate the Properties and Functions of the Microtubule (+) End
  • Other End-Binding Proteins Regulate Microtubule Disassembly
  • 18.4. Kinesins and Dyneins: Microtubule-Based Motor Proteins
  • Organelles in Axons Are Transported Along Microtubules in Both Directions
  • Kinesin-1 Powers Anterograde Transport of Vesicles Down Axons Toward the (+) End of Microtubules
  • Kinesins Form a Large Protein Family with Diverse Functions
  • Kinesin-1 Is a Highly Processive Motor
  • Dynein Motors Transport Organelles Toward the (-) End of Microtubules
  • Kinesins and Dyneins Cooperate in the Transport of Organelles Throughout the Cell
  • Tubulin Modifications Distinguish Different Microtubules and Their Accessibility to Motors
  • 18.5. Cilia and Flagella: Microtubule-Based Surface Structures
  • Eukaryotic Cilia and Flagella Contain Long Doublet Microtubules Bridged by Dynein Motors
  • Ciliary and Flagellar Beating Are Produced by Controlled Sliding of Outer Doublet Microtubules
  • Intraflagellar Transport Moves Material up and down Cilia and Flagella
  • Primary Cilia Are Sensory Organelles on Interphase Cells
  • Defects in Primary Cilia Underlie Many Diseases
  • 18.6. Mitosis
  • Centrosomes Duplicate Early in the Cell Cycle in Preparation for Mitosis
  • Mitosis Can Be Divided into Six Phases
  • Mitotic Spindle Contains Three Classes of Microtubules
  • Microtubule Dynamics Increase Dramatically in Mitosis
  • Mitotic Asters Are Pushed Apart by Kinesin-5 and Oriented by Dynein
  • Chromosomes Are Captured and Oriented During Prometaphase
  • Duplicated Chromosomes Are Aligned by Motors and Microtubule Dynamics
  • Chromosomal Passenger Complex Regulates Microtubule Attachment at Kinetochores
  • Anaphase A Moves Chromosomes to Poles by Microtubule Shortening
  • Anaphase B Separates Poles by the Combined Action of Kinesins and Dynein
  • Additional Mechanisms Contribute to Spindle Formation
  • Cytokinesis Splits the Duplicated Cell in Two
  • Plant Cells Reorganize Their Microtubules and Build a New Cell Wall in Mitosis
  • 18.7. Intermediate Filaments
  • Intermediate Filaments Are Assembled from Subunit Dimers
  • Intermediate Filament Proteins Are Expressed in a Tissue-Specific Manner
  • Intermediate Filaments Are Dynamic
  • Defects in Lamins and Keratins Cause Many Diseases
  • 18.8. Coordination and Cooperation Between Cytoskeletal Elements
  • Intermediate Filament-Associated Proteins Contribute to Cellular Organization
  • Microfilaments and Microtubuies Cooperate to Transport Melanosomes
  • Cdc42 Coordinates Microtubules and Microfilaments During Cell Migration
  • Advancement of Neural Growth Cones Is Coordinated by Microfilaments and Microtubules
  • 19. Eukaryotic Cell Cycle
  • 19.1. Overview of the Cell Cycle and Its Control
  • Cell Cycle Is an Ordered Series of Events Leading to Cell Replication
  • Cyclin-Dependent Kinases Control the Eukaryotic Cell Cycle
  • Several Key Principles Govern the Cell Cycle
  • 19.2. Model Organisms and Methods to Study the Cell Cycle
  • Budding and Fission Yeast Are Powerful Systems for Genetic Analysis of the Cell Cycle
  • Frog Oocytes and Early Embryos Facilitate Biochemical Characterization of the Cell Cycle Engine
  • Fruit Flies Reveal the Interplay Between Development and the Cell Cycle
  • Study of Tissue Culture Cells Uncovers Cell Cycle Regulation in Mammals
  • Researchers Use Multiple Tools to Study the Cell Cycle
  • 19.3. Regulation of CDK Activity
  • Cyclin-Dependent Kinases Are Small Protein Kinases That Require a Regulatory Cyclin Subunit for Their Activity
  • Cyclins Determine the Activity of CDKs
  • Cyclin Levels Are Primarily Regulated by Protein Degradation
  • CDKs Are Regulated by Activating and Inhibitory Phosphorylation
  • CDK Inhibitors Control Cyclin-CDK Activity
  • Special CDK Alleles Led to the Discovery of CDK Functions
  • 19.4. Commitment to the Cell Cycle and DNA Replication
  • Cells Are Irreversibly Committed to Cell Division at a Cell Cycle Point Called START
  • E2F Transcription Factor and Its Regulator Rb Control the G1-S Phase Transition in Metazoans
  • Extracellular Signals Govern Cell Cycle Entry
  • Degradation of an S Phase CDK Inhibitor Triggers DNA Replication
  • Replication at Each Origin Is Initiated Once and Only Once During the Cell Cycle
  • Duplicated DNA Strands Become Linked During Replication
  • 19.5. Entry into Mitosis
  • Precipitous Activation of Mitotic CDKs Initiates Mitosis
  • Mitotic CDKs Promote Nuclear Envelope Breakdown
  • Mitotic CDKs Promote Mitotic Spindle Formation
  • Chromosome Condensation Facilitates Chromosome Segregation
  • 19.6. Completion of Mitosis: Chromosome Segregation and Exit from Mitosis
  • Separase-Mediated Cleavage of Cohesins Initiates Chromosome Segregation
  • APC/C Activates Separase Through Securin Ubiquitinylation
  • Mitotic CDK Inactivation Triggers Exit from Mitosis
  • Cytokinesis Creates Two Daughter Cells
  • 19.7. Surveillance Mechanisms in Cell Cycle Regulation
  • Checkpoint Pathways Establish Dependencies and Prevent Errors in the Cell Cycle
  • Growth Checkpoint Pathway Ensures That Cells Only Enter the Cell Cycle After Sufficient Macromolecule Biosynthesis
  • DNA Damage Response Halts Cell Cycle Progression When DNA Is Compromised
  • Spindle Assembly Checkpoint Pathway Prevents Chromosome Segregation Until Chromosomes Are Accurately Attached to the Mitotic Spindle
  • Spindle Position Checkpoint Pathway Ensures That the Nucleus Is Accurately Partitioned Between Two Daughter Cells
  • 19.8. Meiosis: A Special Type of Cell Division
  • Extracellular and Intracellular Cues Regulate Entry into Meiosis
  • Several Key Features Distinguish Meiosis from Mitosis
  • Recombination and a Meiosis-Specific Cohesin Subunit Are Necessary for the Specialized Chromosome Segregation in Meiosis I
  • Co-orienting Sister Kinetochores Is Critical for Meiosis I Chromosome Segregation
  • DNA Replication Is Inhibited Between the Two Meiotic Divisions
  • Classic Experiment 19.1 Cell Biology Emerging from the Sea: The Discovery of Cyclins
  • pt. IV Cell Growth and Development
  • 20. Integrating Cells Into Tissues
  • 20.1. Cell-Cell and Cell-Matrix Adhesion: An Overview
  • Cell-Adhesion Molecules Bind to One Another and to Intracellular Proteins
  • Extracellular Matrix Participates in Adhesion, Signaling, and Other Functions
  • Evolution of Multifaceted Adhesion Molecules Made Possible the Evolution of Diverse Animal Tissues
  • 20.2. Cell-Cell and Cell-ECM Junctions and Their Adhesion Molecules
  • Epithelial Cells Have Distinct Apical, Lateral, and Basal Surfaces
  • Three Types of Junctions Mediate Many Cell-Cell and Cell-ECM Interactions
  • Cadherins Mediate Cell-Cell Adhesions in Adherens Junctions and Desmosomes
  • Integrins Mediate Cell-ECM Adhesions, Including Those in Epithelial Cell Hemidesmosomes
  • Tight Junctions Seal Off Body Cavities and Restrict Diffusion of Membrane Components
  • Gap Junctions Composed of Connexins Allow Small Molecules to Pass Directly Between Adjacent Cells
  • 20.3. Extracellular Matrix I: The Basal Lamina
  • Basal Lamina Provides a Foundation for Assembly of Cells into Tissues
  • Laminin, a Multi-adhesive Matrix Protein, Helps Cross-link Components of the Basal Lamina
  • Sheet-Forming Type IV Collagen is a Major Structural Component of the Basal Lamina --
  • Contents note continued: Perlecan, a Proteoglycan, Cross-links Components of the Basal Lamina and Cell-Surface Receptors
  • 20.4. Extracellular Matrix II: Connective Tissue
  • Fibrillar Collagens Are the Major Fibrous Proteins in the ECM of Connective Tissues
  • Fibrillar Collagen Is Secreted and Assembled into Fibrils Outside the Cell
  • Type I and II Collagens Associate with Nonfibrillar Collagens to Form Diverse Structures
  • Proteoglycans and Their Constituent GAGs Play Diverse Roles in the ECM
  • Hyaluronan Resists Compression, Facilitates Cell Migration, and Gives Cartilage Its Gel-like Properties
  • Fibronectins Interconnect Cells and Matrix, Influencing Cell Shape, Differentiation, and Movement
  • Elastic Fibers Permit Many Tissues to Undergo Repeated Stretching and Recoiling
  • Metalloproteases Remodel and Degrade the Extracellular Matrix
  • 20.5. Adhesive Interactions in Motile and Nonmotile Cells
  • Integrins Relay Signals between Cells and Their Three-Dimensional Environment
  • Regulation of Integrin-Mediated Adhesion and Signaling Controls Cell Movement
  • Connections Between the ECM and Cytoskeleton Are Defective in Muscular Dystrophy
  • IgCAMs Mediate Cell-Cell Adhesion in Neuronal and Other Tissues
  • Leukocyte Movement into Tissues Is Orchestrated by a Precisely Timed Sequence of Adhesive Interactions
  • 20.6. Plant Tissues
  • Plant Cell Wall Is a Laminate of Cellulose Fibrils in a Matrix of Glycoproteins
  • Loosening of the Cell Wall Permits Plant Cell Growth
  • Plasmodesmata Directly Connect the Cytosols of Adjacent Cells in Higher Plants
  • Only a Few Adhesive Molecules Have Been Identified in Plants
  • 21. Stem Cells, Cell Asymmetry, and Cell Death
  • 21.1. Early Metazoan Development and Embryonic Stem Cells
  • Fertilization Unifies the Genome
  • Cleavage of the Mammalian Embryo Leads to the First Differentiation Events
  • Inner Cell Mass Is the Source of Embryonic Stem (ES) Cells
  • Multiple Factors Control the Pluripotency of ES Cells
  • Animal Cloning Shows That Differentiation Can Be Reversed
  • Somatic Cells Can Generate Induced Pluripotent Stem (iPS) Cells
  • 21.2. Stem Cells and Niches in Multicellular Organisms
  • Stem Cells Give Rise to Both Stem Cells and Differentiating Cells
  • Stem Cells for Different Tissues Occupy Sustaining Niches
  • Germ-Line Stem Cells Produce Sperm and Oocytes
  • Intestinal Stem Cells Continuously Generate All of the Cells of the Intestinal Epithelium
  • Neural Stem Cells Form Nerve and Glial Cells in the Central Nervous System
  • Hematopoietic Stem Cells Form All Blood Cells
  • Meristems Are Niches for Stem Cells in Plants
  • 21.3. Mechanisms of Cell Polarity and Asymmetric Cell Division
  • Cell Polarization and Asymmetry Before Cell Division Follow a Common Hierarchy
  • Polarized Membrane Traffic Allows Yeast to Grow Asymmetrically During Mating
  • Par Proteins Direct Cell Asymmetry in the Nematode Embryo
  • Par Proteins and Other Polarity Complexes Are Involved in Epithelial-Cell Polarity
  • Planar Cell Polarity Pathway Orients Cells within an Epithelium
  • Par Proteins Are Also involved in Asymmetric Cell
  • Division of Stem Cells
  • 21.4. Cell Death and Its Regulation
  • Programmed Cell Death Occurs Through Apoptosis
  • Evolutionarily Conserved Proteins Participate in the Apoptotic Pathway
  • Caspases Amplify the Initial Apoptotic Signal and Destroy Key Cellular Proteins
  • Neurotrophins Promote Survival of Neurons
  • Mitochondria Play a Central Role in Regulation of Apoptosis in Vertebrate Cells
  • Pro-apoptotic Proteins Bax and Bak Form Pores in the Outer Mitochondrial Membrane
  • Release of Cytochrome c and SMAC/DIABLO Proteins from Mitochondria Leads to Formation of the Apoptosome and Caspase Activation
  • Trophic Factors Induce Inactivation of Bad, a Pro-apoptotic BH3-Only Protein
  • Vertebrate Apoptosis Is Regulated by BH3-Only Pro-Apoptotic Proteins That Are Activated by Environmental Stresses
  • Tumor Necrosis Factor and Related Death Signals Promote Cell Murder by Activating Caspases
  • 22. Nerve Cells
  • 22.1. Neurons and Glia: Building Blocks of the Nervous System
  • Information Flows Through Neurons from Dendrites to Axons
  • Information Moves Along Axons as Pulses of Ion Flow Called Action Potentials
  • Information Flows Between Neurons via Synapses
  • Nervous System Uses Signaling Circuits Composed of Multiple Neurons
  • Glial Cells Form Myelin Sheaths and Support Neurons
  • 22.2. Voltage-Gated Ion Channels and the Propagation of Action Potentials
  • Magnitude of the Action Potential Is Close to ENa and Is Caused by Na+ Influx Through Open Na+ Channels
  • 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
  • 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
  • Two Types of Glia Produce Myelin Sheaths
  • 22.3. Communication at Synapses
  • Formation of Synapses Requires Assembly of Presynaptic and Postsynaptic Structures
  • Neurotransmitters Are Transported into Synaptic Vesicles by H+~Linked Antiport Proteins
  • Synaptic Vesicles Loaded with Neurotransmitter Are Localized near the Plasma Membrane
  • Influx of Ca2+ Triggers Release of Neurotransmitters
  • Calcium-Binding Protein Regulates Fusion of Synaptic Vesicles with the Plasma Membrane
  • Fly Mutants Lacking Dynamin Cannot Recycle Synaptic Vesicles
  • Signaling at Synapses 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 an Action Potential
  • Gap Junctions Allow Certain Neurons to Communicate Directly
  • 22.4. Sensing the Environment: Touch, Pain, Taste, and Smell
  • Mechanoreceptors Are Gated Cation Channels
  • Pain Receptors Are Also Gated Cation Channels
  • Five Primary Tastes Are Sensed by Subsets of Cells in Each Taste Bud
  • Plethora of Receptors Detect Odors
  • Each Olfactory Receptor Neuron Expresses a Single Type of Odorant Receptor
  • 23. Immunology
  • 23.1. Overview of Host Defenses
  • Pathogens Enter the Body Through Different Routes and Replicate at Different Sites
  • Leukocytes Circulate Throughout the Body and Take Up Residence in Tissues and Lymph Nodes
  • Mechanical and Chemical Boundaries Form a First Layer of Defense Against Pathogens
  • Innate Immunity Provides a Second Line of Defense After Mechanical and Chemical Barriers Are Crossed
  • Inflammation Is a Complex Response to Injury That Encompasses Both Innate and Adaptive Immunity
  • Adaptive Immunity, the Third Line of Defense, Exhibits Specificity
  • 23.2. Immunoglobulins: Structure and Function
  • Immunoglobulins Have a Conserved Structure Consisting of Heavy and Light Chains
  • Multiple Immunoglobulin Isotypes Exist, Each with Different Functions
  • Each B Cell Produces a Unique, Clonally Distributed Immunoglobulin
  • Immunoglobulin Domains Have a Characteristic Fold Composed of Two β Sheets Stabilized by a Disulfide Bond
  • Immunoglobulin's Constant Region Determines Its Functional Properties
  • 23.3. Generation of Antibody Diversity and B-Cell Development
  • Functional Light-Chain Gene Requires Assembly of V and J Gene Segments
  • Rearrangement of the Heavy-Chain Locus Involves V, D, and J Gene Segments
  • Somatic Hypermutation Allows the Generation and Selection of Antibodies with Improved Affinities
  • B-Cell Development Requires Input from a Pre-B-Cell Receptor
  • During an Adaptive Response, B Cells Switch from Making Membrane-Bound Ig to Making Secreted Ig
  • B Cells Can Switch the Isotype of Immunoglobulin They Make
  • 23.4. MHC and Antigen Presentation
  • MHC Determines the Ability of Two Unrelated Individuals of the Same Species to Accept or Reject Grafts
  • Killing Activity of Cytotoxic T Cells Is Antigen Specific and MHC Restricted
  • T Cells with Different Functional Properties Are Guided by Two Distinct Classes of MHC Molecules
  • MHC Molecules Bind Peptide Antigens and Interact with the T-Cell Receptor
  • Antigen Presentation Is the Process by Which Protein Fragments Are Complexed with MHC Products and Posted to the Cell Surface
  • Class I MHC Pathway Presents Cytosolic Antigens
  • Class II MHC Pathway Presents Antigens Delivered to the Endocytic Pathway
  • 23.6. T Cells, T-Cell Receptors, and T-Cell Development
  • Structure of the T-Cell Receptor Resembles the F(ab) Portion of an Immunoglobulin
  • TCR Genes Are Rearranged in a Manner Similar to Immunoglobulin Genes
  • T Cell Receptors Are Very Diverse, with Many of Their Variable Residues Encoded in the Junctions Between V, D, and J Gene Segments
  • Signaling via Antigen-Specific Receptors Triggers Proliferation and Differentiation of T and B Cells
  • T Cells Capable of Recognizing MHC Molecules Develop Through a Process of Positive and Negative Selection
  • T Cells Require Two Types of Signal for Full Activation
  • Cytotoxic T Cells Carry the CD8 Co-receptor and Are Specialized for Killing
  • T Cells Produce an Array of Cytokines That Provide Signals to Other Immune Cells
  • CD4 T Cells Are Divided into Three Major Classes Based on Their Cytokine Production and Expression of Surface Markers
  • Leukocytes Move in Response to Chemotactic Cues Provided by Chemokines --
  • Contents note continued: 23.6. Collaboration of Immune-System Cells in the Adaptive Response
  • Toll-Like Receptors Perceive a Variety of Pathogen-Derived Macromolecular Patterns
  • Engagement of Toll-Like Receptors Leads to Activation of Antigen-Presenting Cells
  • Production of High-Affinity Antibodies Requires Collaboration Between B and T Cells
  • Vaccines Elicit Protective Immunity Against a Variety of Pathogens
  • Classic Experiment 23.1 Two Genes Become One: Somatic Rearrangement of Immunoglobulin Genes
  • 24. Cancer
  • 24.1. Tumor Cells and the Onset of Cancer
  • Metastatic Tumor Cells Are Invasive and Can Spread
  • Cancers Usually Originate in Proliferating Cells
  • Local Environment Impacts Heterogeneous Tumor Formation by Cancer Stem Cells
  • Tumor Growth Requires Formation of New Blood Vessels
  • Specific Mutations Transform Cultured Cells 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
  • Cancer Cells Differ from Normal Cells in Fundamental Ways
  • DNA Microarray Analysis of Expression Patterns Can Reveal Subtle Differences Between Tumor Cells
  • 24.2. 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
  • Epigenetic Changes Can Contribute to Tumorigenesis
  • 24.3. Cancer and Misregulation of Growth Regulatory Pathways
  • Mouse Models of Human Cancer Teach Us About Disease initiation and Progression
  • Oncogenic 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
  • Aberrations in Signaling Pathways That Control Development Are Associated with Many Cancers
  • Molecular Cell Biology Is Changing How Cancer Is Treated
  • 24.4. Cancer and Mutation of Cell Division and Checkpoint Regulators
  • Mutations That Promote Unregulated Passage from G1 to S Phase Are Oncogenic
  • Loss of p53 Abolishes the DNA Damage Checkpoint
  • Apoptotic Genes Can Function as Proto-oncogenes or Tumor-Suppressor Genes
  • Micro-RNAs Are a New Class of Oncogenic Factors
  • 24.5. Carcinogens and Caretaker Genes in Cancer
  • Carcinogens Induce Cancer by Damaging DNA
  • Some Carcinogens Have Been Linked to Specific Cancers
  • Loss of DNA-Repair Systems Can Lead to Cancer
  • Telomerase Expression Contributes to Immortalization of Cancer Cells.
Other information
  • Includes bibliographical references and index.
  • OCLC
ISBN
  • 9781429234139
  • 142923413X
  • 9781464109812
  • 1464109818
Identifying numbers
  • LCCN: 2012932495
  • OCLC: 171110915
  • OCLC: 171110915

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