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About this Book<br/>Cover Page<br/>Halftitle Page<br/>Title Page<br/>Copyright Page<br/>Dedication<br/>About the Authors<br/>Visual Preface<br/>Preface<br/>Acknowledgments<br/>Brief Contents<br/>Contents<br/>Chapter 1 Evolution: Molecules, Genes, Cells, and Organisms<br/>1.1 The Molecules of Life<br/>Proteins Give Cells Structure and Perform Most Cellular Tasks<br/>Nucleic Acids Carry Coded Information for Making Proteins at the Right Time and Place<br/>Phospholipids Are the Conserved Building Blocks of All Cellular Membranes<br/>Quality Control of All Cellular Macromolecules Is Essential for Life<br/>1.2 Prokaryotic Cell Structure and Function<br/>Prokaryotes Comprise Two Kingdoms: Archaea and Eubacteria<br/>Many Bacteria Including Escherichia coli Are Widely Used in Biological Research<br/>1.3 Eukaryotic Cell Structure and Function<br/>The Cytoskeleton Has Many Important Functions<br/>The Nucleus Contains the DNA Genome, Apparatuses for Synthesis of DNA and RNA, and a Fibrous Matrix<br/>The Endoplasmic Reticulum Is the Site of Synthesis of Most Membrane and Secreted Proteins as Well as Many Lipids<br/>The Golgi Complex Sorts Secreted Proteins and Many Membrane Proteins to Their Final Destinations in the Cell<br/>Endosomes Bring Proteins and Particles from the Outside into Cells<br/>Lysosomes Are Cellular Recycling Centers<br/>Plant Vacuoles Store Water, Ions, and Small-Molecule Nutrients Such as Sugars and Amino Acids<br/>Peroxisomes and Plant Glyoxisomes Metabolize Fatty Acids and Other Small Molecules Without Producing ATP from ADP and Pi<br/>Mitochondria Are the Principal Sites of ATP Production in Aerobic Cells<br/>Chloroplasts Contain Internal Compartments in Which Photosynthesis Takes Place<br/>Many Organelle-Like Structures Are Unbounded by a Membrane<br/>All Eukaryotic Cells Use a Similar Cycle to Regulate Their Division<br/>1.4 Unicellular Eukaryotic Organisms Widely Used in Cell Biology Research<br/>Yeasts Are Used to Study Fundamental Aspects of Eukaryotic Cell Structure and Function<br/>Mutations in Yeast Led to the Identification of Key Cell Cycle Proteins<br/>Studies in the Alga Chlamydomonas reinhardtii Led to the Development of a Powerful Technique to Study Brain Function<br/>The Parasite That Causes Malaria Has Novel Organelles That Allow It to Undergo a Remarkable Life Cycle<br/>1.5 Metazoan Structure, Function, Evolution, and Differentiation<br/>Multicellularity Requires Cell-Cell and Cell-Matrix Adhesions<br/>Epithelia Originated Early in Evolution<br/>Cells Are Organized into Tissues and Tissues into Organs<br/>Genomics Has Revealed Important Aspects of Metazoan Evolution and Cell Function<br/>Development Uses a Conserved Set of Master Transcription Factors and Involves Epigenetic Modifications to DNA and Its Associated Histone Proteins<br/>1.6 Metazoan Organisms Widely Used in Cell Biology Research<br/>Drosophila melanogaster and Caenorhabditis elegans Are Used to Identify Genes That Regulate Animal Development<br/>Planaria Are Used to Study Stem Cells and Tissue Regeneration<br/>Studies on Fish, Mice, and Other Vertebrate Organisms Inform the Study of Human Development and Disease<br/>Human Genetic Diseases Elucidate Important Aspects of Cell Function<br/>Unbiased Single Cell Sequencing Experiments Identify Altogether New Cell Types<br/>The Following Chapters Present Many Experimental Techniques and Much Experimental Data That Explains How We Know What We Know About Cell Structure and Function<br/>Chapter 2 Chemical Foundations<br/>2.1 Covalent Bonds and Noncovalent Interactions<br/>The Electronic Structure of an Atom Determines the Number and Geometry of the Covalent Bonds It Can Make<br/>All Covalent Bonds Are Not Equal: Electrons May Be Shared Equally or Unequally in Covalent Bonds<br/>Covalent Bonds Are Much Stronger and More Stable Than Noncovalent Interactions<br/>Ionic Bonds Are Noncovalent Interactions Formed by the Electrostatic Attractions Between Oppositely Charged Ions<br/>Hydrogen Bonds Are Noncovalent Interactions That Determine the Properties of Water and the Water Solubility of Uncharged Molecules<br/>Van der Waals Interactions Are Weak Attractive Interactions Caused by Transient Dipoles<br/>The Hydrophobic Effect Causes Nonpolar Molecules to Adhere to One Another<br/>Molecular Complementarity Due to Noncovalent Interactions Leads to a Lock-and-Key Fit Between Biomolecules<br/>2.2 Chemical Building Blocks of Cells<br/>Amino Acids Differing Only in Their Side Chains Compose Proteins<br/>Five Different Nucleotides Are Used to Build Nucleic Acids<br/>Monosaccharides Covalently Assemble into Linear and Branched Polysaccharides<br/>Phospholipids Associate Noncovalently to Form the Basic Bilayer Structure of Biomembranes<br/>2.3 Chemical Reactions and Chemical Equilibrium<br/>A Chemical Reaction Is in Equilibrium When the Rates of the Forward and Reverse Reactions Are Equal<br/>The Equilibrium Constant Reflects the Extent of a Chemical Reaction<br/>Chemical Reactions in Cells Are at Steady State<br/>Dissociation Constants of Binding Reactions Reflect the Affinity of Interacting Molecules<br/>Biological Fluids Have Characteristic pH Values<br/>Hydrogen Ions Are Released by Acids and Taken Up by Bases<br/>Buffers Maintain the pH of Intracellular and Extracellular Fluids<br/>2.4 Biochemical Energetics<br/>Several Forms of Energy Are Important in Biological Systems<br/>Cells Can Transform One Type of Energy into Another<br/>The Change in Free Energy Determines If a Chemical Reaction Will Occur Spontaneously<br/>The ΔG°′ of a Reaction Can Be Calculated from Its Keq<br/>The Rate of a Reaction Depends on the Activation Energy Necessary to Energize the Reactants into a Transition State<br/>Life Depends on the Coupling of Energetically Unfavorable Chemical Reactions with Energetically Favorable Ones<br/>Hydrolysis of ATP Releases Substantial Free Energy and Drives Many Cellular Processes<br/>ATP Is Generated During Photosynthesis and Respiration<br/>NAD+ and FAD Couple Many Biological Oxidation and Reduction Reactions<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 3 Protein Structure and Function<br/>3.1 Hierarchical Structure of Proteins<br/>The Primary Structure of a Protein Is Its Linear Arrangement of Amino Acids<br/>Secondary Structures Are the Core Elements of Protein Architecture<br/>Structural Motifs Are Regular Combinations of Secondary Structures<br/>Tertiary Structure Is the Overall Folding of a Polypeptide Chain<br/>Different Ways of Depicting the Conformation of Proteins Convey Different Types of Information<br/>Domains Are Modules of Tertiary Structure<br/>Comparing Protein Sequences and Structures Provides Insight into Protein Function and Evolution<br/>There Are Four Broad Structural Categories of Proteins<br/>Multiple Polypeptides Assemble into Quaternary Structures, Supramolecular Complexes, and Biomolecular Condensates<br/>3.2 Protein Folding<br/>Planar Peptide Bonds Limit the Shapes into Which Proteins Can Fold<br/>Protein Folding Is Promoted by Proline Isomerases<br/>The Amino Acid Sequence of a Protein Determines How It Will Fold<br/>Folding of Proteins In Vivo Is Promoted by Chaperones<br/>Abnormally Folded Proteins Can Form Amyloids That Are Implicated in Diseases<br/>3.3 Protein Binding and Enzyme Catalysis<br/>Specific Binding of Ligands Underlies the Functions of Most Proteins<br/>Enzymes Are Highly Efficient and Specific Catalysts<br/>An Enzyme’s Active Site Binds Substrates and Carries Out Catalysis<br/>Serine Proteases Demonstrate How an Enzyme’s Active Site Works<br/>Enzymes in a Common Pathway Are Often Physically Associated with One Another<br/>3.4 Regulating Protein Function<br/>Regulated Synthesis and Degradation of Proteins Is a Fundamental Property of Cells<br/>The Proteasome Is a Molecular Machine Used to Degrade Proteins<br/>Ubiquitin Marks Cytosolic Proteins for Degradation in Proteasomes<br/>Noncovalent Binding Permits Allosteric, or Cooperative, Regulation of Proteins<br/>Noncovalent Binding of Calcium and GTP Are Widely Used as Allosteric Switches to Control Protein Activity<br/>Covalent Modification of Proteins Can Regulate their Activities<br/>Phosphorylation and Dephosphorylation Covalently Regulate Protein Activity<br/>The Structure and Function of Protein Kinase A Is Typical of Many Kinases<br/>Protein Kinase Activity Is Often Regulated by Phosphorylation of the Kinase<br/>Ubiquitinylation and Deubiquitinylation Covalently Regulate Protein Activity<br/>Proteolytic Cleavage Irreversibly Activates or Inactivates Some Proteins<br/>Higher Order Regulation Includes Control of Protein Location<br/>3.5 Purifying, Detecting, and Characterizing Proteins<br/>Centrifugation Can Separate Particles and Molecules That Differ in Mass or Density<br/>Electrophoresis Separates Molecules on the Basis of Their Charge-to-Mass Ratio<br/>Liquid Chromatography Resolves Proteins by Mass, Charge, or Affinity<br/>Highly Specific Enzyme and Antibody Assays Can Detect Individual Proteins<br/>Radioisotopes Are Indispensable Tools for Detecting Biological Molecules<br/>Mass Spectrometry Can Determine the Mass and Sequence of Proteins<br/>Protein Primary Structure Can Be Determined by Chemical Methods and from Gene Sequences<br/>Protein Conformation Is Determined by Sophisticated Physical Methods<br/>3.6 Proteomics<br/>Proteomics Is the Study of All or a Large Subset of Proteins in a Biological System<br/>Advanced Techniques in Mass Spectrometry Are Critical to Proteomic Analysis<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 4 Culturing and Visualizing Cells<br/>4.1 Growing and Studying Cells in Culture<br/>Culture of Animal Cells Requires Nutrient-Rich Media and Special Solid Surfaces<br/>Primary Cell Cultures and Cell Strains Have a Finite Life Span<br/>Transformed Cells Can Grow Indefinitely in Culture<br/>Flow Cytometry Separates Different Cell Types<br/>Growth of Cells in Two-Dimensional and Three-Dimensional Culture Mimics the In Vivo Environment<br/>Stem Cells Can Differentiate in Culture to Make Organoids<br/>Hybridomas Produce Abundant Monoclonal Antibodies<br/>A Wide Variety of Cell Biological Processes Can Be Studied with Cultured Cells<br/>Drugs Are Commonly Used in Cell Biological Research<br/>4.2 Light Microscopy: Exploring Cell Structure and Visualizing Proteins Within Cells<br/>The Resolution of the Conventional Light Microscope Is About 0.2 μm<br/>Phase-Contrast and Differential-Interference-Contrast Microscopy Visualize Unstained Live Cells<br/>Imaging Subcellular Details Often Requires That Specimens Be Fixed, Sectioned, and Stained<br/>Fluorescence Microscopy Can Localize and Quantify Specific Molecules in Live Cells<br/>Intracellular Ion Concentrations Can Be Determined with Ion-Sensitive Fluorescent Dyes<br/>Immunofluorescence Microscopy Can Detect Specific Proteins in Fixed Cells<br/>Tagging with Fluorescent Proteins Allows the Visualization of Specific Proteins in Live Cells<br/>Deconvolution and Confocal Microscopy Enhance Visualization of Three-Dimensional Fluorescent Objects<br/>Two-Photon Excitation Microscopy Allows Imaging Deep into Tissue Samples<br/>TIRF Microscopy Provides Exceptional Imaging in One Focal Plane<br/>FRAP Reveals the Dynamics of Cellular Components<br/>FRET Measures Distance Between Fluorochromes<br/>Optogenetics Allows Light to Regulate Events in a Spatial and Temporal Manner<br/>Point Source Fluorescent Objects Can Be Located at Nanometer Resolution<br/>Super-Resolution Microscopy Can Localize Proteins to Nanometer Accuracy<br/>Light-Sheet Microscopy Can Rapidly Image Cells in Living Tissue<br/>4.3 Electron Microscopy: High-Resolution Imaging<br/>Single Molecules or Structures Can Be Imaged Using a Negative Stain or Metal Shadowing<br/>Cells and Tissues Are Cut into Thin Sections for Viewing by Electron Microscopy<br/>Immunoelectron Microscopy Localizes Proteins at the Ultrastructural Level<br/>Cryoelectron Microscopy Allows Visualization of Specimens Without Fixation or Staining<br/>Scanning Electron Microscopy of Metal-Coated Specimens Reveals Surface Features<br/>4.4 Isolation of Cell Organelles<br/>Disruption of Cells Releases Their Organelles and Other Contents<br/>Centrifugation Can Separate Many Types of Organelles<br/>Organelle-Specific Antibodies Are Useful in Preparing Highly Purified Organelles<br/>Proteomics Reveals the Protein Composition of Organelles<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 5 Fundamental Molecular Genetic Mechanisms<br/>5.1 The Double-Helical Structure of DNA<br/>Native DNA Is a Double Helix of Complementary Antiparallel Strands<br/>DNA Can Undergo Reversible Strand Separation<br/>DNA Molecules Can Acquire Torsional Stress<br/>5.2 DNA Replication<br/>DNA Polymerases Require a Template and a Primer to Replicate DNA<br/>Duplex DNA Is Unwound, and Daughter Strands Are Formed at the DNA Replication Fork<br/>A DNA Replication Fork Advances by Cooperation of Multiple Proteins<br/>DNA Replication Occurs Bidirectionally from Each Origin<br/>5.3 DNA Repair and Recombination<br/>Chemical and Radiation Damage to DNA Can Lead to Mutations<br/>High-Fidelity DNA Excision-Repair Systems Recognize and Repair Damage<br/>Base Excision Repairs T-G Mismatches and Damaged Bases<br/>Mismatch Excision Repairs Other Mismatches and Small Insertions and Deletions<br/>Nucleotide Excision Repairs Chemical Adducts That Distort Normal DNA Shape<br/>Two Systems Use Recombination to Repair Double-Strand Breaks in DNA<br/>Homologous Recombination Can Repair DNA Damage and Generate Genetic Diversity<br/>5.4 Transcription of Protein-Coding Genes and Formation of mRNA<br/>A Template DNA Strand Is Transcribed into a Complementary RNA Strand by RNA Polymerase<br/>Eukaryotic Precursor mRNAs Are Processed to Form Functional mRNAs<br/>Alternative RNA Splicing Increases the Number of Proteins That Can Be Expressed from a Single Eukaryotic Gene<br/>5.5 The Decoding of mRNA by tRNAs<br/>Messenger RNA Carries Information from DNA in a Three-Letter Genetic Code<br/>The Folded Structure of tRNA Promotes Its Decoding Functions<br/>Nonstandard Base Pairing Often Occurs Between Codons and Anticodons<br/>Amino Acids Are Linked to Their Cognate tRNAs with Great Accuracy<br/>5.6 Stepwise Synthesis of Proteins on Ribosomes<br/>Ribosomes Are Protein-Synthesizing Machines<br/>Methionyl-tRNAiMet Recognizes the AUG Start Codon<br/>Eukaryotic Translation Initiation Usually Occurs at the First AUG Downstream from the 5′ End of an mRNA<br/>During Chain Elongation Each Incoming Aminoacyl-tRNA Moves Through Three Ribosomal Sites<br/>Translation Is Terminated by Release Factors When a Stop Codon Is Reached<br/>Polysomes and Rapid Ribosome Recycling Increase the Efficiency of Translation<br/>GTPase-Superfamily Proteins Function in Several Quality-Control Steps of Translation<br/>Nonsense Mutations Can Be Bypassed by Suppressing tRNA Mutations<br/>5.7 Viruses: Parasites of the Cellular Genetic System<br/>Most Viral Host Ranges Are Narrow<br/>Viral Capsids Are Regular Arrays of One or a Few Types of Protein<br/>Lytic Viral Growth Cycles Lead to Death of Host Cells<br/>Viral DNA Is Integrated into the Host-Cell Genome in Some Nonlytic Viral Growth Cycles<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 6 Molecular Genetic Techniques<br/>6.1 Using Genetic Analysis of Mutations to Identify and Study Genes<br/>Recessive and Dominant Mutant Alleles Generally Have Opposite Effects on Gene Function<br/>Segregation of Mutations in Breeding Experiments Reveals Whether They Are Dominant or Recessive<br/>Conditional Mutations Can Be Used to Study Essential Genes in Yeast<br/>Recessive Lethal Mutations in Diploids Can Be Identified by Inbreeding and Maintained in Heterozygotes<br/>Complementation Tests Determine Whether Different Recessive Mutations Are in the Same Gene<br/>Double Mutants Are Useful in Assessing the Order in Which Proteins Function<br/>Genetic Suppression and Synthetic Lethality Can Reveal Interacting or Redundant Proteins<br/>Global Analysis of Double Mutant Combinations Can Reveal Networks of Gene Functions<br/>6.2 DNA Cloning and Characterization<br/>Restriction Enzymes and DNA Ligases Allow Insertion of DNA Fragments into Cloning Vectors<br/>Isolated DNA Fragments Can Be Cloned into E. coli Plasmid Vectors<br/>Yeast Genomic Libraries Can Be Constructed with Shuttle Vectors and Screened by Functional Complementation<br/>cDNA Libraries Represent the Sequences of Protein-Coding Genes<br/>The Polymerase Chain Reaction Amplifies a Specific DNA Sequence from a Complex Mixture<br/>Cloned DNA Molecules Can Be Sequenced Rapidly by Methods Based on PCR<br/>6.3 Using Sequence Information to Identify Genes and Deduce Their Function<br/>Most Genes Can Be Readily Identified Within Genomic DNA Sequences<br/>Bioinformatic Principles Can Be Used to Deduce the Likely Functional Consequences of Mutations<br/>The Function and Evolutionary Origins of Genes and Proteins Can Be Deduced from Their Sequence<br/>Comparison of Related Sequences from Different Species Can Give Clues to Evolutionary Relationships Among Proteins<br/>Biological Complexity of an Organism Is Not Directly Related to the Number of Protein-Coding Genes in the Genome<br/>6.4 Locating and Identifying Genes That Specify Human Traits<br/>Monogenic Diseases Show One of Three Patterns of Inheritance<br/>DNA Polymorphisms Are Used as Markers for Linkage Mapping of Human Mutations<br/>Human Linkage Studies Can Map Disease Genes with a Resolution of About 1 Mbp<br/>Further Analysis Is Needed to Locate a Disease Gene in Cloned DNA<br/>Most Inherited Diseases Result from Multiple Genetic Defects<br/>Identifying Component Genetic Risk Factors of Complex Traits<br/>Medically Important Genes Can Be Identified by Alleles That Protect Against Disease<br/>Identification of Causative Mutations in Cancer Cells<br/>6.5 Using Cloned DNA Fragments to Study Gene Expression<br/>In Situ Hybridization Techniques Permit Detection of Specific mRNAs<br/>DNA Microarrays Can Be Used to Evaluate the Expression of Many Genes at Once<br/>Cluster Analysis of Multiple Expression Experiments Identifies Co-Regulated Genes<br/>Sequencing of cDNAs Allows Analysis of Gene Expression in Individual Cells<br/>E. coli Expression Systems Can Produce Large Quantities of Proteins from Cloned Genes<br/>Plasmid Expression Vectors Can Be Designed for Use in Animal Cells<br/>6.6 Altering the Function of Specific Genes by Design<br/>Normal Yeast Genes Can Be Replaced with Mutant Alleles by Homologous Recombination<br/>Engineered CRISPR Systems Allow Precise Genome Editing<br/>Somatic Cell Recombination Can Inactivate Genes in Specific Tissues of Mice<br/>RNA Interference Causes Gene Inactivation by Destroying the Corresponding mRNA<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 7 Genes, Chromatin, and Chromosomes<br/>7.1 Eukaryotic Gene Structure and Organization<br/>Most Genes of Multicellular Eukaryotes Contain Introns and Produce mRNAs Encoding Single Proteins<br/>Simple and Complex Transcription Units Are Found in Eukaryotic Genomes<br/>Protein-Coding Genes May Be Solitary or Belong to a Gene Family<br/>Heavily Used Gene Products Are Encoded by Multiple Copies of Genes<br/>Nonprotein-Coding Genes Encode Functional RNAs<br/>7.2 Chromosomal Organization of Genes and Noncoding DNA<br/>Genomes of Many Organisms Contain a Large Fraction of Noncoding DNA<br/>Most Simple-Sequence DNAs Are Concentrated in Specific Chromosomal Locations<br/>DNA Fingerprinting Depends on Differences in Length of Simple-Sequence DNAs<br/>Unclassified Intergenic DNA Occupies a Significant Portion of the Genome<br/>7.3 Transposable (Mobile) DNA Elements<br/>Movement of Mobile Elements Involves a DNA or an RNA Intermediate<br/>Most Mobile Elements in Bacteria Are DNA Transposons Known as Insertion Sequences<br/>Eukaryotic DNA Transposons Move Using a Cut-and-Paste Process<br/>LTR Retrotransposons Behave Like Intracellular Retroviruses<br/>Non-LTR Retrotransposons Transpose by a Distinct Mechanism<br/>Other Retroposed RNAs Are Found in Genomic DNA<br/>Mobile DNA Elements Have Significantly Influenced Evolution<br/>7.4 Structural Organization of Eukaryotic Chromatin and Chromosomes<br/>Chromatin Structure<br/>Chromatin Structure Is Conserved Among Eukaryotes<br/>Chromatin Is a Disordered Chain of Nucleosomes Packed Together at Different Concentration Densities in the Nucleus<br/>Modifications of Histone Tails Control Chromatin Condensation and Function<br/>Additional Nonhistone Proteins Regulate Transcription and Replication<br/>7.5 Morphology and Functional Elements of Eukaryotic Chromosomes<br/>Chromosome Number, Size, and Shape at Metaphase Are Species-Specific<br/>During Metaphase, Chromosomes Can Be Distinguished by Banding Patterns and Chromosome Painting<br/>Chromosome Painting and DNA Sequencing Reveal the Evolution of Chromosomes<br/>Interphase Polytene Chromosomes Arise by DNA Amplification<br/>Three Functional Elements Are Required for Replication and Stable Inheritance of Chromosomes<br/>Centromere Sequences Vary Greatly in Length and Complexity<br/>Addition of Telomeric Sequences by Telomerase Prevents Shortening of Chromosomes<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 8 Transcriptional Control of Gene Expression<br/>8.1 Overview of Eukaryotic Transcription<br/>Regulatory Elements in Eukaryotic DNA Are Found Both Close to and Many Kilobases Away from Transcription Start Sites<br/>Three Eukaryotic Nuclear RNA Polymerases Catalyze Formation of Different RNAs<br/>The Clamp Domain Enables RNA Polymerase II to Transcribe Long Stretches of DNA<br/>The Largest Subunit in RNA Polymerase II Has an Essential Carboxy-Terminal Repeat<br/>8.2 RNA Polymerase II Promoters and General Transcription Factors<br/>RNA Polymerase II Initiates Transcription at DNA Sequences Corresponding to the 5′ Cap of mRNAs<br/>The TATA Box, Initiators, and CpG Islands Function as Promoters in Eukaryotic DNA<br/>General Transcription Factors Position RNA Polymerase II at Transcription Start Sites and Assist in Initiation<br/>Elongation Factors Regulate the Initial Stages of Transcription in the Promoter-Proximal Region<br/>8.3 Regulatory Sequences for Protein-Coding Genes and the Proteins Through Which They Function<br/>Promoter-Proximal Elements Help Regulate Eukaryotic Genes<br/>Distant Enhancers Often Stimulate Transcription by RNA Polymerase II<br/>Most Eukaryotic Genes Are Regulated by Multiple Transcription-Control Elements<br/>DNase I Footprinting and EMSA Detect Protein-DNA Interactions<br/>Activators Are Composed of Distinct Functional Domains<br/>Repressors Are the Functional Converse of Activators<br/>DNA-Binding Domains Can Be Classified into Numerous Structural Types<br/>Structurally Diverse Activation and Repression Domains Regulate Transcription<br/>Transcription Factor Interactions Increase Gene-Control Options<br/>Multiprotein Complexes Form on Enhancers<br/>8.4 Molecular Mechanisms of Transcription Repression and Activation<br/>Formation of Heterochromatin Silences Gene Expression at Telomeres, near Centromeres, and in Other Regions<br/>Repressors Can Direct Histone Deacetylation at Specific Genes<br/>Activators Can Direct Histone Acetylation at Specific Genes<br/>Chromatin-Remodeling Complexes Help Activate or Repress Transcription<br/>Pioneer Transcription Factors Initiate the Process of Gene Activation During Cellular Differentiation<br/>The Mediator Complex Forms a Molecular Bridge Between Activation Domains and Pol II<br/>Transcriptional Condensates Greatly Increase the Rate of Transcription Initiation<br/>Transcription Occurs in Bursts<br/>8.5 Regulation of Transcription-Factor Activity<br/>DNase I Hypersensitive Sites Reflect the Developmental History of Cellular Differentiation<br/>Nuclear Receptors Are Regulated by Lipid-Soluble Hormones<br/>All Nuclear Receptors Share a Common Domain Structure<br/>Nuclear-Receptor Response Elements Contain Inverted or Direct Repeats<br/>Hormone Binding to a Nuclear Receptor Regulates Its Activity as a Transcription Factor<br/>Metazoans Regulate the RNA Polymerase II Transition from Initiation to Elongation<br/>Termination of Transcription Is Also Regulated<br/>8.6 Epigenetic Regulation of Transcription<br/>DNA Methylation Regulates Transcription<br/>Methylation of Specific Histone Lysines Is Linked to Epigenetic Mechanisms of Gene Repression<br/>Epigenetic Control by Polycomb and Trithorax Complexes<br/>Long Noncoding RNAs Direct Epigenetic Repression in Metazoans<br/>8.7 Other Eukaryotic Transcription Systems<br/>Transcription Initiation by Pol I and Pol III Is Analogous to That by Pol II<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 9 Post-Transcriptional Gene Control<br/>9.1 Processing of Eukaryotic Pre-mRNA<br/>The 5′ Cap Is Added to Nascent RNAs Shortly After Transcription Initiation<br/>Chain Elongation by RNA Polymerase II Is Coupled to the Presence of RNA Processing Factors<br/>A Diverse Set of Proteins with Conserved RNA-Binding Domains Associate with Pre-mRNAs<br/>Splicing Occurs at Short, Conserved Sequences in Pre-mRNAs via Two Transesterification Reactions<br/>During Splicing, snRNAs Base-Pair with Pre-mRNA to Select Splice Sites and Guide the Transesterification Reactions<br/>Spliceosomes Catalyze Pre-mRNA Splicing<br/>3′ Cleavage and Polyadenylation of Pre-mRNAs Are Tightly Coupled<br/>9.2 Regulation of Pre-mRNA Processing<br/>Additional Nuclear Proteins Contribute to Splice-Site Selection in the Long Pre-mRNAs of Humans and Other Vertebrates<br/>Expression and Function of Related K+-Channel Protein Isoforms in Vertebrate Inner Ear Hair Cells<br/>Regulation of RNA Splicing Through Splicing Enhancers and Silencers Controls Drosophila Sexual Differentiation<br/>Splicing Repressors and Activators Control Splicing at Alternative Sites<br/>Expression of Dscam Isoforms in Drosophila Retinal Neurons<br/>Abnormal RNA Splicing and Disease<br/>Self-Splicing Group II Introns Provide Clues to the Evolution of snRNAs<br/>Nuclear Exonucleases and the Exosome Degrade RNA That Is Processed out of Pre-mRNAs<br/>RNA Processing Solves the Problem of Pervasive Transcription of the Genome in Mammalian Cells<br/>RNA Editing Alters the Sequences of Some Pre-mRNAs<br/>9.3 Transport of mRNA Across the Nuclear Envelope<br/>SR Proteins Mediate Nuclear Export of mRNA<br/>Pre-mRNAs Associated with Spliceosomes Are Not Exported from the Nucleus<br/>HIV Rev Protein Regulates the Transport of Unspliced Viral mRNAs<br/>9.4 Cytoplasmic Mechanisms of Post-Transcriptional Control<br/>The Concentration of an mRNA in the Cytoplasm Is Determined by Its Rate of Synthesis and Its Rate of Degradation<br/>Degradation of mRNAs in the Cytoplasm Occurs by Several Mechanisms<br/>MicroRNAs Repress Translation and Induce Degradation of Specific mRNAs<br/>RNA Interference Induces Degradation of Precisely Complementary mRNAs<br/>Cytoplasmic Polyadenylation Promotes Translation of Some mRNAs<br/>Protein Synthesis Can Be Globally Regulated<br/>Sequence-Specific RNA-Binding Proteins Control Specific mRNA Translation<br/>Surveillance Mechanisms Prevent Translation of Improperly Processed mRNAs<br/>Localization of mRNAs Permits Production of Proteins at Specific Regions Within the Cytoplasm<br/>9.5 Processing of rRNA and tRNA<br/>Pre-rRNA Genes Are Similar in All Eukaryotes and Function as Nucleolar Organizers<br/>Small Nucleolar RNAs Assist in Processing Pre-rRNAs<br/>Self-Splicing Group I Introns Were the First Examples of Catalytic RNA<br/>Pre-tRNAs Undergo Extensive Modification in the Nucleus<br/>9.6 Nuclear Bodies Are Functionally Specialized Nuclear Domains<br/>Cajal Bodies<br/>Nuclear Speckles<br/>Nuclear Paraspeckles<br/>Promyelocytic Leukemia (PML) Nuclear Bodies<br/>Nucleolar Functions in Addition to Ribosomal Subunit Synthesis<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 10 Biomembrane Structure<br/>10.1 The Lipid Bilayer: Composition and Structural Organization<br/>Phospholipids Spontaneously Form Bilayers<br/>Phospholipid Bilayers Form a Sealed Compartment Surrounding an Internal Aqueous Space<br/>Biomembranes Contain Three Principal Classes of Lipids<br/>Most Lipids and Many Proteins Are Laterally Mobile in Biomembranes<br/>Lipid Composition Influences the Physical Properties of Membranes<br/>Lipid Composition Is Different in the Exoplasmic and Cytosolic Leaflets<br/>Cholesterol and Sphingolipids Cluster with Specific Proteins in Membrane Microdomains<br/>Cells Store Excess Lipids in Lipid Droplets<br/>10.2 Membrane Proteins: Structure and Basic Functions<br/>Proteins Interact with Membranes in Three Different Ways<br/>Most Transmembrane Proteins Have Membrane-Spanning α Helices<br/>Multiple β Strands in Porins Form Membrane-Spanning “Barrels”<br/>Covalently Attached Lipids Anchor Some Proteins to Membranes<br/>All Transmembrane Proteins and Glycolipids Are Asymmetrically Oriented in the Bilayer<br/>Lipid-Binding Motifs Help Target Peripheral Proteins to the Membrane<br/>Proteins Can Be Removed from Membranes by Detergents or High-Salt Solutions<br/>10.3 Phospholipids, Sphingolipids, and Cholesterol: Synthesis and Intracellular Movement<br/>Fatty Acids Are Assembled from Two-Carbon Building Blocks by Several Important Enzymes<br/>Small Cytosolic Proteins Facilitate Movement of Fatty Acids<br/>Fatty Acids Are Incorporated into Phospholipids Primarily on the ER Membrane<br/>Flippases Move Phospholipids from One Membrane Leaflet to the Opposite Leaflet<br/>Cholesterol Is Synthesized by Enzymes in the Cytosol and ER Membrane<br/>Cholesterol and Phospholipids Are Transported Between Organelles by Several Mechanisms<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 11 Transmembrane Transport of Ions and Small Molecules<br/>11.1 Overview of Transmembrane Transport<br/>Only Gases and Small Uncharged Molecules Cross Membranes by Simple Diffusion<br/>Three Main Classes of Membrane Proteins Transport Molecules and Ions Across Cellular Membranes<br/>11.2 Facilitated Transport of Glucose and Water<br/>Uniport Transport Is Faster and More Specific than Simple Diffusion<br/>The Low Km of the GLUT1 Uniporter Enables It to Transport Glucose into Most Mammalian Cells<br/>The Human Genome Encodes a Family of Sugar-Transporting GLUT Proteins<br/>Transport Proteins Can Be Studied Using Artificial Membranes and Recombinant Cells<br/>Osmotic Pressure Causes Water to Move Across Membranes<br/>Aquaporins Increase the Water Permeability of Cellular Membranes<br/>11.3 ATP-Powered Pumps and the Intracellular Ionic Environment<br/>There Are Four Main Classes of ATP-Powered Pumps<br/>ATP-Powered Ion Pumps Generate and Maintain Ionic Gradients Across Cellular Membranes<br/>Muscle Relaxation Depends on Ca2+ ATPases That Pump Ca2+ from the Cytosol into the Sarcoplasmic Reticulum<br/>The Mechanism of Action of the Ca2+ Pump Is Known in Detail<br/>The Na+/K+ ATPase Maintains the Intracellular Na+ and K+ Concentrations in Animal Cells<br/>V-Class H+ ATPases Maintain the Acidity of Lysosomes and Vacuoles<br/>ABC Proteins Export a Wide Variety of Drugs and Toxins from the Cell<br/>Certain ABC Proteins “Flip” Phospholipids and Other Lipid-Soluble Substrates from One Membrane Leaflet to the Other<br/>The ABC Cystic Fibrosis Transmembrane Regulator Is a Chloride Channel, Not a Pump<br/>11.4 Nongated Ion Channels and the Resting Membrane Potential<br/>Selective Movement of Ions Creates a Transmembrane Electric Gradient<br/>The Resting Membrane Potential in Animal Cells Depends Largely on the Outward Flow of K+ Ions Through Open K+ Channels<br/>Ion Channels Are Selective for Certain Ions by Virtue of a Molecular Selectivity Filter<br/>Patch Clamps Permit Measurement of Ion Movements Through Single Channels<br/>Novel Ion Channels Can Be Characterized by a Combination of Oocyte Expression and Patch Clamping<br/>11.5 Cotransport by Symporters and Antiporters<br/>Na+ Entry into Mammalian Cells Is Thermodynamically Favored<br/>Na+-Linked Symporters Enable Animal Cells to Import Sugars Including Glucose and Galactose as Well as Amino Acids Against High Concentration Gradients<br/>A Bacterial Na+/Amino Acid Symporter Reveals How Symport Works<br/>A Na+-Linked Ca2+ Antiporter Regulates the Strength of Cardiac Muscle Contraction<br/>Several Cotransporters Regulate Cytosolic pH<br/>An Anion Antiporter Is Essential for Transport of CO2 by Erythrocytes<br/>Numerous Transport Proteins Enable Plant Vacuoles to Accumulate Metabolites and Ions<br/>11.6 Transcellular Transport<br/>Multiple Transport Proteins Are Needed to Move Glucose and Amino Acids Across Epithelia<br/>Simple Rehydration Therapy Depends on the Osmotic Gradient Created by Absorption of Glucose and Na+<br/>Parietal Cells Acidify the Stomach Contents While Maintaining a Neutral Cytosolic pH<br/>Bone Resorption Requires the Coordinated Function of a V-Class Proton Pump and a Specific Chloride Channel<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 12 Cellular Energetics<br/>12.1 Chemiosmosis, Electron Transport, the Proton-Motive Force, and ATP Synthesis<br/>12.2 First Step of Harvesting Energy from Glucose: Glycolysis<br/>During Glycolysis (Stage I), Cytosolic Enzymes Convert Glucose to Pyruvate<br/>The Rate of Glycolysis Is Adjusted to Meet the Cell’s Need for ATP<br/>Glucose Is Fermented When Oxygen Is Scarce<br/>12.3 The Structure of Mitochondria<br/>Mitochondria Are Abundant, Multifunctional Organelles<br/>Mitochondria Have Two Structurally and Functionally Distinct Membranes<br/>Mitochondria Contain DNA and Evolved from a Single Endosymbiotic Event Involving Alphaproteobacterium<br/>The Size, Structure, and Coding Capacity of mtDNA Vary Considerably Among Organisms<br/>Mitochondrial DNA Is Located in the Matrix and Transferred During Mitosis to Daughter Cells by Cytoplasmic Inheritance<br/>Products of Mitochondrial Genes Are Not Exported<br/>Mitochondrial Genetic Codes Can Differ from the Standard Nuclear Code<br/>Mutations in Mitochondrial DNA Cause Several Genetic Diseases in Humans<br/>12.4 The Dynamics of Mitochondria and Mitochondrial-ER Membrane Contact Sites<br/>Mitochondria Are Dynamic Organelles<br/>Mitochondrial Function and Dynamics Can Depend on Direct Contacts with Other Organelles<br/>12.5 The Citric Acid Cycle and Fatty Acid Oxidation<br/>In the First Part of Stage II, Pyruvate Is Converted to Acetyl CoA and High-Energy Electrons<br/>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<br/>Transporters in the Inner Mitochondrial Membrane Help Maintain Appropriate Cytosolic and Matrix Concentrations of NAD+ and NADH<br/>Mitochondrial Oxidation of Fatty Acids Generates ATP<br/>Peroxisomal Oxidation of Fatty Acids Generates No ATP<br/>12.6 The Electron-Transport Chain and Generation of the Proton-Motive Force<br/>Oxidation of NADH and FADH2 Releases a Substantial Amount of Energy<br/>Electron Transport in Mitochondria Is Coupled to Proton Pumping<br/>Electrons Release Energy as They Flow Downhill Through a Series of Electron Carriers<br/>Four Large Multiprotein Complexes (I–IV) Couple Electron Transport to Proton Pumping Across the Inner Mitochondrial Membrane<br/>The Reduction Potentials of Electron Carriers in the Electron-Transport Chain Favor Electron Flow from NADH to O2<br/>The Multiprotein Complexes of the Electron-Transport Chain Assemble into Supercomplexes<br/>Reactive Oxygen Species Are By-Products of Electron Transport<br/>Experiments Using Purified Electron-Transport Chain Complexes Established the Stoichiometry of Proton Pumping<br/>The Proton-Motive Force in Mitochondria Is Due Largely to a Voltage Gradient Across the Inner Membrane<br/>12.7 Harnessing the Proton-Motive Force to Synthesize ATP<br/>The Mechanism of ATP Synthesis Is Shared Among Bacteria, Mitochondria, and Chloroplasts<br/>ATP Synthase Comprises F0 and F1 Multiprotein Complexes<br/>Rotation of the F1γ Subunit, Driven by Proton Movement Through F0, Powers ATP Synthesis<br/>Multiple Protons Must Pass Through ATP Synthase to Synthesize One ATP<br/>F0 c Ring Rotation Is Driven by Protons Flowing Through Transmembrane Channels<br/>ATP-ADP Exchange and Phosphate Transport Across the Inner Mitochondrial Membrane Are Required to Supply ADP and Phosphate for ATP Synthesis<br/>The Rate of Mitochondrial Oxidation Normally Depends on ADP Levels<br/>Mitochondria in Brown Fat Use the Proton-Motive Force to Generate Heat<br/>12.8 Chloroplasts and Photosynthesis<br/>Thylakoid Membranes in Chloroplasts Are the Sites of Photosynthesis in Plants<br/>Chloroplasts Contain Large DNAs Often Encoding More Than a Hundred Proteins<br/>Light Absorption by Photosystems in Chloroplasts Provides the Energy That Drives the Synthesis of NADPH and ATP and the Generation of O2 from H2O<br/>Three of the Four Stages in Photosynthesis Occur on the Thylakoid Membrane and Only During Illumination<br/>Stages 1 and 2 of Photosynthesis Convert Sunlight into High Energy Electrons That Generate a Proton-Motive Force and NADPH<br/>Core Antenna Complexes and Light-Harvesting Complexes Increase the Efficiency of Photosynthesis<br/>Multiple Mechanisms Protect Cells Against Damage from Reactive Oxygen Species During Photoelectron Transport<br/>12.9 Use of Light Energy to Generate Molecular Oxygen, NADPH, and ATP in Stages 1–3 of Photosynthesis<br/>The First Three Stages of Photosynthesis<br/>Relative Activities of Photosystems I and II Are Regulated<br/>12.10 ATP and NADPH Drive Carbon Fixation in the Calvin Cycle and Carbohydrate Synthesis in Stage 4 of Photosynthesis<br/>Rubisco Fixes CO2 in the Chloroplast Stroma<br/>Photorespiration Competes with Carbon Fixation and Is Reduced in C4 Plants<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 13 Moving Proteins into Membranes and Organelles<br/>13.1 Targeting Proteins to and Across the ER Membrane<br/>Pulse-Chase Experiments with Purified ER Membranes Demonstrated That Secreted Proteins Cross the ER Membrane<br/>A Hydrophobic N-Terminal Signal Sequence Targets Nascent Secretory Proteins to the ER<br/>Cotranslational Translocation Is Initiated by Two GTP-Hydrolyzing Proteins<br/>Passage of Growing Polypeptides Through the Translocon Is Driven by Translation<br/>ATP Hydrolysis Powers Post-Translational Translocation of Some Secretory Proteins in Yeast<br/>13.2 Insertion of Membrane Proteins into the ER<br/>Several Topological Classes of Integral Membrane Proteins Are Synthesized on the ER<br/>Internal Stop-Transfer Anchor and Signal-Anchor Sequences Determine Topology of Single-Pass Proteins<br/>Type IV (Multipass) Proteins<br/>A Phospholipid Anchor Tethers Some Cell-Surface Proteins to the Membrane<br/>The Topology of a Membrane Protein Can Often Be Deduced from Its Sequence<br/>13.3 Protein Modifications, Folding, and Quality Control in the ER<br/>A Preformed N-Linked Oligosaccharide Is Added to Many Proteins in the Rough ER<br/>Oligosaccharide Side Chains May Promote Folding and Stability of Glycoproteins<br/>Disulfide Bonds Are Formed and Rearranged by Proteins in the ER Lumen<br/>Chaperones and Other ER Proteins Facilitate Folding and Assembly of Proteins<br/>Improperly Folded Proteins in the ER Induce Expression of Protein-Folding Catalysts<br/>Unassembled or Misfolded Proteins in the ER Are Often Transported to the Cytosol for Degradation<br/>13.4 Targeting of Proteins to Mitochondria and Chloroplasts<br/>Amphipathic N-Terminal Targeting Sequences Direct Proteins to the Mitochondrial Matrix<br/>Mitochondrial Protein Import Requires Outer-Membrane Receptors and Translocons in Both Membranes<br/>Studies with Chimeric Proteins Demonstrate Important Features of Mitochondrial Protein Import<br/>Three Energy Inputs Are Needed to Import Proteins into Mitochondria<br/>Multiple Signals and Pathways Target Proteins to Submitochondrial Compartments<br/>Import of Chloroplast Stromal Proteins Is Similar to Import of Mitochondrial Matrix Proteins<br/>Proteins Are Targeted to Thylakoids by Mechanisms Related to Bacterial Protein Translocation<br/>13.5 Targeting of Peroxisomal Proteins<br/>A Cytosolic Receptor Targets Proteins with an SKL Sequence at the C-Terminus to the Peroxisomal Matrix<br/>Peroxisomal Membrane and Matrix Proteins Are Incorporated by Different Pathways<br/>13.6 Transport into and out of the Nucleus<br/>Large and Small Molecules Enter and Leave the Nucleus via Nuclear Pore Complexes<br/>Nuclear Transport Receptors Escort Proteins Containing Nuclear-Localization Signals into the Nucleus<br/>A Second Type of Nuclear Transport Receptor Escorts Proteins Containing Nuclear-Export Signals out of the Nucleus<br/>Most mRNAs Are Exported from the Nucleus by a Ran-Independent Mechanism<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 14 Vesicular Traffic, Secretion, and Endocytosis<br/>14.1 Techniques for Studying the Secretory Pathway<br/>Transport of a Protein Through the Secretory Pathway Can Be Assayed in Live Cells<br/>Yeast Mutants Define Major Stages and Components of Vesicular Transport<br/>Cell-Free Transport Assays Allow Dissection of Individual Steps in Vesicular Transport<br/>14.2 Molecular Mechanisms of Vesicle Budding and Fusion<br/>Assembly of a Protein Coat Drives Vesicle Formation and Selection of Cargo Molecules<br/>A Conserved Set of GTPase Switch Proteins Controls the Assembly of Different Vesicle Coats<br/>Targeting Sequences on Cargo Proteins Make Specific Molecular Contacts with Coat Proteins<br/>Rab GTPases Control Docking of Vesicles on Target Membranes<br/>Paired Sets of SNARE Proteins Mediate Fusion of Vesicles with Target Membranes<br/>Dissociation of SNARE Complexes After Membrane Fusion Is Driven by ATP Hydrolysis<br/>14.3 Early Stages of the Secretory Pathway<br/>COPII Vesicles Mediate Transport from the ER to the Golgi<br/>COPI Vesicles Mediate Retrograde Transport Within the Golgi and from the Golgi to the ER<br/>Anterograde Transport Through the Golgi Occurs by Cisternal Maturation<br/>14.4 Later Stages of the Secretory Pathway<br/>Vesicles Coated with Clathrin and Adapter Proteins Mediate Transport from the trans-Golgi<br/>Dynamin Is Required for Pinching Off of Clathrin-Coated Vesicles<br/>Mannose 6-Phosphate Residues Target Resident Enzymes to Lysosomes<br/>Study of Lysosomal Storage Diseases Revealed Key Components of the Lysosomal Sorting Pathway<br/>Protein Aggregation in the trans-Golgi May Function in Sorting Proteins to Regulated Secretory Vesicles<br/>Some Proteins Undergo Proteolytic Processing After Leaving the trans-Golgi<br/>Distinct Pathways Sort Membrane Proteins to the Apical or Basolateral Region of Polarized Cells<br/>14.5 Receptor-Mediated Endocytosis<br/>Cells Take Up Lipids from the Blood in the Form of Large, Well-Defined Lipoprotein Complexes<br/>Receptors for Macromolecular Ligands Contain Sorting Signals That Target Them for Endocytosis<br/>The Acidic pH of Late Endosomes Causes Most Receptor-Ligand Complexes to Dissociate<br/>Receptor-Mediated Endocytosis Can Down-Regulate Signaling Receptors<br/>14.6 Directing Membrane Proteins and Cytosolic Materials to the Lysosome for Degradation<br/>Multivesicular Endosomes Segregate Membrane Proteins Destined for the Lysosomal Membrane from Proteins Destined for Lysosomal Degradation<br/>Retroviruses Bud from the Plasma Membrane by a Process Similar to Formation of Multivesicular Endosomes<br/>The Autophagic Pathway Delivers Cytosolic Proteins or Entire Organelles to Lysosomes<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 15 Receptors, Hormones, and Cell Signaling<br/>15.1 Signal Transduction Pathways: From Extracellular Signal to Cellular Response<br/>Signaling Molecules Can Act Locally or at a Distance<br/>Signal Transduction Pathways Can Produce Rapid, Short-Term or Slow, Long-Term Changes in Cells, or Both<br/>Receptors Are Allosteric Proteins That Activate Signal Transduction Pathways<br/>Receptors Can Be in the Cytosol, Nucleus, or on the Cell Surface Membrane<br/>Most Receptors Bind Only a Single Type of Ligand or a Group of Closely Related Ligands<br/>Most Receptors Bind Their Ligands with High Affinity<br/>Second Messengers Are Used in Most Signal Transduction Pathways<br/>Protein Kinases and Phosphatases Participate in Signal Transduction Pathways by Covalently Modifying and Thus Activating or Inhibiting a Wide Variety of Proteins That Control Cellular States<br/>GTP-Binding Proteins Are Frequently Used in Signal Transduction Pathways as On/Off Switches<br/>Signal Amplification and Feedback Repression Characterize Most Signal Transduction Pathways<br/>15.2 Studying Cell-Surface Receptors and Signal Transduction Proteins<br/>Binding Assays Are Used to Detect Receptors and Determine Their Affinity and Specificity for Ligands<br/>Near-Maximal Cellular Response to a Signaling Molecule Usually Does Not Require Activation of All Receptors<br/>Sensitivity of a Cell to External Signals Is Determined by the Number of Cell-Surface Receptors and Their Affinity for Ligand<br/>Chemical Analogs of Signaling Molecules Are Used to Study Receptors and Are Widely Used as Drugs<br/>Receptors Can Be Purified by Affinity Chromatography Techniques<br/>Immunoprecipitation Assays and Affinity Techniques Can Be Used to Study the Activity of Protein Kinases<br/>Immunoprecipitation of Kinases<br/>Western Blotting with a Monoclonal Antibody Specific for a Phosphorylated Amino Acid in a Protein<br/>GTP-Binding Signal Transduction Proteins Can Be Isolated and Their Activities Measured Using Pull-Down Assays<br/>Concentrations of Free Ca2+ in the Mitochondrial Matrix, ER, and Cytosol Can Be Measured with Targeted Fluorescent Proteins<br/>15.3 Structure and Mechanism of G Protein–Coupled Receptors<br/>All G Protein–Coupled Receptors Share the Same Basic Structure<br/>Ligand-Activated G Protein–Coupled Receptors Catalyze Exchange of GTP for GDP on the α Subunit of a Heterotrimeric G Protein<br/>Different G Proteins Are Activated by Different GPCRs and in Turn Regulate Different Effector Proteins<br/>Analysis of GPCRs Has Identified Important Human Hormones<br/>15.4 Regulating Metabolism of Many Cells: G Protein–Coupled Receptors That Activate or Inhibit Adenylyl Cyclase<br/>Adenylyl Cyclase Is Stimulated and Inhibited by Different Receptor-Ligand Complexes<br/>cAMP Activates Protein Kinase A by Releasing Its Inhibitory Subunits<br/>Glycogen Catabolism Is Stimulated by Hormone-Induced Activation of PKA<br/>Signal Amplification Occurs in the cAMP-PKA Glycogen Degradation Pathway<br/>cAMP-Mediated Activation of PKA Produces Diverse Responses in Different Cell Types<br/>CREB Links cAMP and PKA to Activation of Gene Transcription<br/>Anchoring Proteins Localize Effects of cAMP to Specific Regions of the Cell<br/>Multiple Feedback Mechanisms Suppress Signaling by the GPCR/cAMP/PKA Pathway<br/>15.5 Regulating Protein Secretion and Muscle Contraction: Ca2+ Ions as Second Messengers in Multiple Signal Transduction Pathways<br/>Products of the Hydrolysis of the Membrane Lipid Phosphatidylinositol 4,5-Bisphosphate by Phospholipase C Elevate Cytosolic Ca2+ Levels<br/>Ca2+ Release from the ER Triggered by IP3<br/>IP3-triggered Ca2+ Transport from the ER to the Mitochondrial Matrix<br/>The Store-Operated Ca2+ Channel in the Plasma Membrane<br/>Feedback Loops in ER and Cytosol Cycling of Ca2+ Trigger Oscillations in the Cytosolic Ca2+ Concentration<br/>DAG Activates Protein Kinase C<br/>Integration of Ca2+ and cAMP Second Messengers Regulates Glycogenolysis<br/>15.6 Vision: How the Eye Senses Light<br/>Light Activates Rhodopsin in Rod Cells of the Eye<br/>Activation of Rhodopsin by Light Leads to Closing of cGMP-Gated Cation Channels<br/>Signal Amplification Makes the Rhodopsin Signal Transduction Pathway Exquisitely Sensitive<br/>Rapid Termination of the Rhodopsin Signal Transduction Pathway Is Essential for the Temporal Resolution of Vision<br/>Termination of the Signal from Light-Activated Rhodopsin (R*) by Rhodopsin Phosphorylation and Binding of Arrestin<br/>Termination of the Signal from Activated Gαt ⋅ GTP by GTP Hydrolysis<br/>Rod Cells Adapt to Varying Levels of Ambient Light by Intracellular Trafficking of Arrestin and Transducin<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 16 Growth Factor and Cytokine Signaling Pathways That Control Gene Expression<br/>16.1 Growth Factors and Their Receptor Tyrosine Kinases<br/>Binding of Ligand to the Extracellular Domain of an RTK Leads to Dimerization and Activation of Its Intrinsic Cytosolic Tyrosine Kinase<br/>Homo- and Hetero-Oligomers of Epidermal Growth Factor Receptors Bind Members of the Epidermal Growth Factor Family<br/>EGF Receptor Homodimers<br/>EGF Receptor Heterodimers with HER2<br/>Ligand Binding to the EGF Receptor and Receptor Dimerization Results in the Formation of an Active Asymmetric Kinase Domain Dimer<br/>Signal Transduction After Activation of RTKs: Phosphotyrosine Residues on the Receptor Are Binding Surfaces for Multiple Proteins with SH2 Domains<br/>Receptor-Mediated Endocytosis and Lysosomal Degradation Squelch Signaling from RTKs<br/>16.2 The Ras/MAP Kinase Signal Transduction Pathway<br/>Ras, a GTPase Switch Protein, Operates Downstream of Most RTKs and Cytokine Receptors<br/>Receptor Tyrosine Kinases Are Linked to Ras by Adapter Proteins<br/>Binding of Sos to Inactive Ras Causes a Conformational Change That Triggers an Exchange of GTP for GDP<br/>Signals Pass from Activated Ras to a Cascade of Protein Kinases Ending with MAP Kinase<br/>MAP Kinase Regulates the Activity of Many Transcription Factors Controlling Early Response Genes<br/>Multiple Feedback Mechanisms Restrain MAP Kinase Activation<br/>Scaffold Proteins Isolate Distinct MAP Kinase Pathways in the Same Cell from One Another<br/>16.3 Phosphoinositide Signal Transduction Pathways<br/>Phospholipase Cγ Is Activated by Many RTKs and Cytokine Receptors<br/>Recruitment of PI-3 Kinase to Activated Receptors Leads to Accumulation of Phosphatidylinositol-3-Phosphates in the Plasma Membrane and to Activation of Several Downstream Kinases<br/>Activated Protein Kinase B Induces Many Cellular Responses<br/>The PI-3 Kinase Pathway Is Negatively Regulated by PTEN Phosphatase<br/>16.4 Cytokines, Cytokine Receptors, and the JAK/STAT Signaling Pathway<br/>Cytokines Regulate the Development and Function of Many Cell Types<br/>Binding of a Cytokine to Its Receptor Activates One or More Tightly Bound JAK Protein Tyrosine Kinases<br/>JAK Kinases Phosphorylate and Activate STAT Transcription Factors<br/>Multiple Mechanisms Suppress Signaling from Cytokine Receptors<br/>Phosphotyrosine Phosphatases<br/>SOCS Proteins<br/>16.5 The TGF-β Family of Growth Factors, Their Receptor Serine Kinases, and the Smad Transcription Factors They Activate<br/>TGF-β Proteins Are Stored in an Inactive Form in the Extracellular Matrix<br/>Three Separate TGF-β Receptor Proteins Participate in Binding TGF-β and Activating Signal Transduction<br/>Activated RI TGF-β Receptors Phosphorylate Smad Transcription Factors<br/>The R-Smad/co-Smad Complex Activates Expression of Different Genes in Different Cell Types<br/>Negative Feedback Loops Restrain TGF-β/Smad Signaling<br/>16.6 Signal Transduction Pathways That Utilize Regulated, Site-Specific Protein Cleavage: Notch/Delta and EGF Precursors<br/>On Binding Delta, the Notch Receptor Is Cleaved, Releasing a Component Transcription Factor<br/>Metalloproteases Catalyze Cleavage of Many Signaling Proteins from the Cell Surface<br/>16.7 Signal Transduction Pathways That Utilize Proteasomal Degradation of Signaling Components: Wnt, Hedgehog, and the Many Hormones That Activate NF-κB<br/>Wnt Signaling Prevents Destruction of a Transcription Factor by a Cytosolic Protein Complex<br/>Concentration Gradients of Wnt Protein Are Essential for Many Steps in Development<br/>Hedgehog Signaling Relieves Repression of Target Gene Expression<br/>Processing of Hh Precursor Protein<br/>The Hh Receptors Patched and Smoothened and the Downstream Signaling Pathway Were Initially Elucidated by Genetic Studies of Drosophila Development<br/>Feedback Regulation of Hh Signaling<br/>Hedgehog Signaling in Vertebrates Requires Primary Cilia<br/>Degradation of an Inhibitor Protein Activates the NF-κB Transcription Factor<br/>Enormous Signalsomes with Polyubiquitin Chain Scaffolds Link Many Cell Surface Receptors to Downstream Proteins in the NF-κB Pathway<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 17 Cell Organization and Movement I: Microfilaments<br/>17.1 Microfilaments and Actin Structures<br/>Actin Is Ancient, Abundant, and Highly Conserved<br/>G-Actin Monomers Assemble into Long, Helical F-Actin Polymers<br/>F-Actin Has Structural and Functional Polarity<br/>17.2 Dynamics of Actin Filaments<br/>Actin Polymerization In Vitro Proceeds in Three Steps<br/>Actin Filaments Grow Faster at (+) Ends than at (−) Ends<br/>Actin Filament Treadmilling Is Accelerated by Profilin and Cofilin<br/>Thymosin-β4 Provides a Reservoir of Actin for Polymerization<br/>Capping Proteins Block Assembly and Disassembly at Actin Filament Ends<br/>17.3 Mechanisms of Actin Filament Assembly<br/>Formins Assemble Unbranched Filaments<br/>The Arp2/3 Complex Nucleates Branched Filament Assembly<br/>Intracellular Movements Can Be Powered by Actin Polymerization<br/>Microfilaments Function in Endocytosis<br/>Toxins That Perturb the Pool of Actin Monomers Are Useful for Studying Actin Dynamics<br/>17.4 Organization of Actin-Based Cellular Structures<br/>Cross-Linking Proteins Organize Actin Filaments into Bundles or Networks<br/>Adapter Proteins Link Actin Filaments to Membranes<br/>17.5 Myosins: Actin-Based Motor Proteins<br/>Myosins Have Head, Neck, and Tail Domains with Distinct Functions<br/>Myosins Make Up a Large Family of Mechanochemical Motor Proteins<br/>Conformational Changes in the Myosin Head Couple ATP Hydrolysis to Movement<br/>Myosin Heads Take Discrete Steps Along Actin Filaments<br/>17.6 Myosin-Powered Movements<br/>Myosin Thick Filaments and Actin Thin Filaments in Skeletal Muscle Slide Past Each Other During Contraction<br/>Skeletal Muscle Is Structured by Stabilizing and Scaffolding Proteins<br/>Contraction of Skeletal Muscle Is Regulated by Ca2+ and Actin-Binding Proteins<br/>Actin and Myosin II Form Contractile Bundles in Nonmuscle Cells<br/>Myosin-Dependent Mechanisms Regulate Contraction in Smooth Muscle and Nonmuscle Cells<br/>Myosin V Carries Vesicles Along Actin Filaments<br/>17.7 Cell Migration: Mechanism, Signaling, and Chemotaxis<br/>Cell Migration Coordinates Force Generation with Cell Adhesion and Membrane Recycling<br/>The Small GTP-Binding Proteins Cdc42, Rac, and Rho Control Actin Organization<br/>Cell Migration Involves the Coordinate Regulation of Cdc42, Rac, and Rho<br/>Migrating Cells Are Steered by Chemotactic Molecules<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 18 Cell Organization and Movement II: Microtubules and Intermediate Filaments<br/>18.1 Microtubule Structure and Organization<br/>Microtubule Walls Are Polarized Structures Built from αβ-Tubulin Dimers<br/>Microtubules Are Assembled from MTOCs to Generate Diverse Configurations<br/>18.2 Microtubule Dynamics<br/>Individual Microtubules Exhibit Dynamic Instability<br/>Localized Assembly and Search and Capture Help Organize Microtubules<br/>Drugs Affecting Tubulin Polymerization Are Useful Experimentally and in Treatment of Diseases<br/>18.3 Regulation of Microtubule Structure and Dynamics<br/>Microtubules Are Stabilized by Side-Binding Proteins<br/>+TIPs Regulate the Properties and Functions of the Microtubule (+) End<br/>Other End-Binding Proteins Also Promote Microtubule Disassembly<br/>Severing Proteins Also Regulate Microtubule Dynamics<br/>18.4 Kinesins and Dyneins: Microtubule-Based Motor Proteins<br/>Organelles in Axons Are Transported Along Microtubules in Both Directions<br/>Kinesin-1 Powers Anterograde Transport of Vesicles Down Axons Toward the (+) Ends of Microtubules<br/>The Kinesins Form a Large Protein Superfamily with Diverse Functions<br/>Kinesin-1 Is a Processive Motor<br/>Dynein Motors Transport Organelles Toward the (−) Ends of Microtubules<br/>Kinesins and Dyneins Cooperate in the Transport of Organelles Throughout the Cell<br/>Tubulin Modifications Distinguish Different Classes of Microtubules and Their Accessibility to Motors<br/>18.5 Cilia and Flagella: Microtubule-Based Surface Structures<br/>Eukaryotic Cilia and Flagella Contain Long Doublet Microtubules Bridged by Dynein Motors<br/>Ciliary and Flagellar Beating Are Produced by Controlled Sliding of Outer Doublet Microtubules<br/>Intraflagellar Transport Moves Material Up and Down Cilia and Flagella<br/>Primary Cilia Are Sensory Organelles on Interphase Cells<br/>Defects in Primary Cilia Underlie Many Diseases<br/>18.6 Mitosis<br/>Centrosomes Duplicate Early in the Cell Cycle in Preparation for Mitosis<br/>Mitosis Can Be Divided into Five Stages<br/>The Mitotic Spindle Contains Three Classes of Microtubules<br/>Microtubule Dynamics Increase Dramatically in Mitosis<br/>Chromosomes Are Captured and Oriented During Prometaphase<br/>Duplicated Chromosomes Are Aligned by Motors and Microtubule Dynamics<br/>The Chromosomal Passenger Complex Regulates Microtubule Attachment at Kinetochores<br/>Anaphase A Moves Chromosomes to Poles by Microtubule Shortening<br/>Anaphase B Separates Poles by the Combined Action of Kinesins and Dynein<br/>The Spindle Is Centered and Oriented by a Dynein/Dynactin-Dependent Pathway<br/>Cytokinesis Splits the Duplicated Cell in Two<br/>Plant Cells Reorganize Their Microtubules and Build a New Cell Wall in Mitosis<br/>18.7 Intermediate Filaments<br/>Intermediate Filaments Are Assembled from Subunit Dimers<br/>Intermediate Filaments Are Dynamic<br/>Cytoplasmic Intermediate Filament Proteins Are Expressed in a Tissue-Specific Manner<br/>Lamins Line the Inner Nuclear Envelope to Provide Organization and Rigidity to the Nucleus<br/>Lamins Are Reversibly Disassembled by Phosphorylation During Mitosis<br/>18.8 Coordination and Cooperation Between Cytoskeletal Elements<br/>Intermediate Filament–Associated Proteins Contribute to Cellular Organization<br/>Microfilaments and Microtubules Cooperate to Transport Melanosomes<br/>Cdc42 Coordinates Microtubules and Microfilaments During Cell Migration<br/>Advancement of Neural Growth Cones Is Coordinated by Microfilaments and Microtubules<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 19 The Eukaryotic Cell Cycle<br/>19.1 Overview of the Cell Cycle<br/>G1 Controls Entry into S Phase<br/>G2 Phase Readies the Cell for Mitosis and Cell Division<br/>Mitosis and Cytokinesis Occur During M-Phase<br/>19.2 Model Organisms and Methods of Studying the Cell Cycle<br/>Budding and Fission Yeasts Are Powerful Systems for Genetic Analysis of the Cell Cycle<br/>Frog Oocytes and Early Embryos Facilitate Biochemical Characterization of the Cell Cycle Machinery<br/>The Study of Tissue Culture Cells Uncovers Cell Cycle Regulation in Mammals<br/>Researchers Use Multiple Tools to Study the Cell Cycle<br/>19.3 Cell Cycle Progression and Control: Feedback Loops and Post-Translational Modification<br/>Cyclin-Dependent Kinases Are Small Protein Kinases That Require a Regulatory Cyclin Subunit for Their Activity<br/>Cyclins Determine the Activity of CDKs<br/>CDKs Are Regulated by Activating and Inhibitory Phosphorylation<br/>CDK Inhibitors Provide Additional Control of Cyclin-CDK Activity<br/>Cyclin Levels Are Regulated by Transcriptional Activation and Ubiquitin-Mediated Protein Degradation<br/>Phosphoserine/Threonine-Binding Domains Build Feedback Loops That Coordinate CDK Activation and Cell Cycle Progression<br/>Mass Spectrometry Studies and Genetically Engineered CDKs Led to the Discovery of New CDK Substrates and Functions<br/>19.4 The Transition from G1 into S Phase and DNA Replication<br/>The G1/S Transition in Budding Yeast Is Controlled by Cyclin-CDK Complexes<br/>The G1–S Phase Transition in Metazoans Involves Cyclin-CDK Control of the E2F Transcription Factor Through Its Regulator Rb<br/>Extracellular Signals Govern Cell Cycle Entry<br/>Degradation of an S Phase CDK Inhibitor Triggers DNA Replication<br/>Replication at Each Origin Is Initiated Once and Only Once During the Cell Cycle<br/>Duplicated DNA Strands Become Linked During Replication<br/>19.5 The G2/M Transition and the Irreversible Engine of Mitosis<br/>Precipitous Activation of Mitotic CDKs by Positive Feedback Loops Initiates Mitosis<br/>Mitotic CDKs Promote Nuclear Envelope Breakdown<br/>Centrosomes Duplicate During S phase and Separate During Mitosis<br/>Mitotic CDKs, Polo-like Kinases, and Aurora Kinases Drive Assembly of a Mitotic Spindle That Attaches to the Kinetochores of Condensed Chromosomes<br/>Chromosome Condensation Facilitates Chromosome Segregation<br/>19.6 The Mitotic Spindle, Chromosome Segregation, and Exit from Mitosis<br/>Separase-Mediated Cleavage of Cohesins Initiates Chromosome Segregation<br/>APC/C Activates Separase Through Securin Ubiquitinylation<br/>Mitotic CDK Inactivation and Protein De-phosphorylation Triggers Exit from Mitosis<br/>Cytokinesis Creates Two Daughter Cells<br/>19.7 Surveillance Mechanisms in Cell Cycle Regulation<br/>The DNA Damage Response System Halts Cell Cycle Progression and Recruits DNA Repair Machinery When DNA Is Compromised<br/>The Spindle Assembly Checkpoint Pathway Prevents Chromosome Segregation Until Chromosomes Are Accurately Attached to the Mitotic Spindle<br/>19.8 Meiosis: A Special Type of Cell Division<br/>Extracellular and Intracellular Cues Regulate Germ Cell Formation<br/>Several Features Distinguish Meiosis from Mitosis<br/>Recombination and a Meiosis-Specific Cohesin Subunit Are Necessary for the Specialized Chromosome Segregation in Meiosis I<br/>Co-orienting Sister Kinetochores Is Critical for Meiosis I Chromosome Segregation<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 20 Integrating Cells into Tissues<br/>20.1 Cell-Cell and Cell–Extracellular Matrix Adhesion: An Overview<br/>Cell-Adhesion Molecules Bind to One Another and to Intracellular Proteins<br/>The Extracellular Matrix Participates in Adhesion, Signaling, and Other Functions<br/>The Evolution of Multifaceted Adhesion Molecules Enabled the Evolution of Diverse Animal Tissues<br/>Cell-Adhesion Molecules Mediate Mechanotransduction<br/>20.2 Cell-Cell and Cell–Extracellular Matrix Junctions and Their Adhesion Molecules<br/>Epithelial Cells Have Distinct Apical, Lateral, and Basal Surfaces<br/>Three Types of Junctions Mediate Many Cell-Cell and Cell-Matrix Interactions<br/>Cadherins Mediate Cell-Cell Adhesions in Adherens Junctions and Desmosomes<br/>Integrins Mediate Cell-Matrix Adhesions, Including Those in Epithelial-Cell Hemidesmosomes<br/>Tight Junctions Seal Off Body Cavities and Restrict Diffusion of Membrane Components<br/>Gap Junctions Composed of Connexins Allow Small Molecules to Pass Directly Between the Cytosols of Adjacent Cells<br/>Tunneling Nanotubes Can Mediate Metabolic Coupling and Transfer Organelles Between Animal Cells<br/>20.3 The Extracellular Matrix I: The Basal Lamina<br/>The Basal Lamina Provides a Foundation for Assembly of Cells into Tissues<br/>Laminin, a Multi-Adhesive Matrix Protein, Helps Cross-Link Components of the Basal Lamina<br/>Sheet-Forming Type IV Collagen Is a Major Structural Component of the Basal Lamina<br/>Perlecan, a Proteoglycan, Cross-Links Components of the Basal Lamina and Cell-Surface Receptors<br/>20.4 The Extracellular Matrix II: Connective Tissue<br/>Fibrillar Collagens Are the Major Fibrous Proteins in the ECM of Connective Tissues<br/>Fibrillar Collagen Is Secreted and Assembled into Fibrils Outside the Cell<br/>Type I and II Collagens Associate with Nonfibrillar Collagens to Form Diverse Structures<br/>Proteoglycans and Their Constituent GAGs Play Diverse Roles in the ECM<br/>Hyaluronan Resists Compression, Facilitates Cell Migration, and Gives Cartilage Its Gel-Like Properties<br/>Fibronectins Connect Cells and ECM, Influencing Cell Shape, Differentiation, and Movement<br/>Elastic Fibers Permit Many Tissues to Undergo Repeated Stretching and Recoiling<br/>Metalloproteases Remodel and Degrade the Extracellular Matrix<br/>20.5 Adhesive Interactions in Motile and Nonmotile Cells<br/>Integrins Mediate Adhesion and Relay Signals Between Cells and Their Three-Dimensional Environment<br/>Regulation of Integrin-Mediated Adhesion and Signaling Controls Cell Function and Movement<br/>Connections Between the ECM and Cytoskeleton Are Defective in Muscular Dystrophy<br/>IgCAMs Mediate Cell-Cell Adhesion in Neural and Other Tissues<br/>Leukocyte Movement into Tissues Is Orchestrated by a Precisely Timed Sequence of Adhesive Interactions<br/>20.6 Plant Tissues<br/>The Plant Cell Wall, a Plant’s ECM, Is a Laminate of Cellulose Fibrils in a Matrix of Polysaccharides and Glycoproteins<br/>Loosening of the Cell Wall Permits Plant Cell Growth<br/>Plasmodesmata Directly Connect the Cytosols of Adjacent Cells<br/>The Molecules That Plants Depend on for Adhesion and Mechanotransduction Differ from Those in Animals<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 21 Responding to the Cellular Environment<br/>21.1 Regulating Blood Glucose Level<br/>Insulin and Glucagon Work Together to Maintain a Stable Blood Glucose Level<br/>A Rise in Blood Glucose Triggers Insulin Secretion from the β Islet Cells<br/>In Fat and Muscle Cells, Insulin Triggers Fusion of Intracellular Vesicles Containing the GLUT4 Glucose Transporter with the Plasma Membrane, Thus Increasing the Rate of Glucose Uptake<br/>In the Liver, Insulin Inhibits Glucose Synthesis, Accelerates the Rate of Glycolysis, and Enhances Storage of Glucose as Glycogen<br/>21.2 Integrating Cell Growth Signals with Nutrient and Energy Levels<br/>The Active mTORC1 Complex Activates Many Anabolic Signal Transduction Pathways<br/>mTORC1 Kinase Activation Requires Amino Acids, a High ATP:AMP Ratio, and Activation of Signal Transduction Pathways Downstream of Growth-Factor Receptors<br/>21.3 Responding to Changes in the Levels of Cholesterol and Unsaturated Fatty Acids<br/>Fatty Acid and Cholesterol Biosynthesis as Well as Cholesterol Import Are Regulated at the Level of Gene Transcription<br/>The Endoplasmic Reticulum SCAP Protein Senses the Level of Cellular Cholesterol<br/>Regulated Intramembrane Proteolysis of SREBP in the Golgi Releases a bHLH Transcription Factor That Acts to Maintain Appropriate Phospholipid and Cholesterol Levels<br/>21.4 Responding to Low Oxygen<br/>Induction of the Erythropoietin Gene at Low Oxygen Levels<br/>Oxygen Sensing and Regulated Hif-1α Expression Is a Property of All Nucleated Mammalian Cells<br/>Hif-1α Function and Stability Are Blocked at Ambient Oxygen Levels<br/>A Conserved Family of Oxygen-Sensitive Transcription Factors Found in Plants and Animals Is Regulated by Post-Translational Addition of an Arginine Residue<br/>21.5 Responding to Elevated Temperatures<br/>The Heat-Shock Response Is Induced by Unfolded Polypeptide Chains<br/>The Heat-Shock Response Is Regulated Primarily by Related Transcription Factors in All Eukaryotes Called Heat-Shock Factors, Including HSF1 in Humans<br/>21.6 Sensing Night and Day: Circadian Rhythms<br/>The Circadian Clock in Most Organisms Relies on a Negative Feedback Loop<br/>The Circadian Clock in Bacteria: A Different Solution<br/>Suprachiasmatic Nucleus: The Master Clock in Mammals<br/>21.7 Sensing and Responding to the Physical Environment<br/>The Hippo Kinase Cascade Pathway in Drosophila and Mammals<br/>Regulation of the Hippo Kinase Cascade by Cell Interactions with the Extracellular Matrix and by Tension on Actin Filaments<br/>The Hippo Pathway and Early Embryogenesis<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 22 Stem Cells, Cell Asymmetry, and Regulated Cell Death<br/>22.1 Early Mammalian Development, Embryonic Stem Cells, and Induced Pluripotent Stem Cells<br/>Fertilization Unifies the Genome<br/>Cleavage of the Mammalian Embryo Leads to the First Differentiation Events<br/>Pluripotent Cells of the Inner Cell Mass Are the Source of ES Cells<br/>Multiple Factors Control the Pluripotency of ES Cells<br/>Animal Cloning Shows That Epigenetic Changes During Differentiation Can Be Reversed<br/>Somatic Cells Can Generate iPS Cells<br/>Patient-Specific iPS Cells Can Be Used to Develop Potential Treatments for Many Diseases<br/>ES and iPS Cells Can Generate Functional Differentiated Human Cells<br/>22.2 Stem Cells and Niches in Multicellular Organisms<br/>Adult Planarians Contain Pluripotent Stem Cells<br/>Multipotent Somatic Stem Cells Give Rise to Both Stem Cells and Differentiating Cells<br/>Stem Cells for Different Tissues Occupy Sustaining Niches<br/>Germ-Line Stem Cells in Many Organisms Produce Sperm or Oocytes<br/>Intestinal Stem Cells Continuously Generate All the Cells of the Intestinal Epithelium<br/>Wnt and R-Spondins Are Essential for Function of the Lgr5+ Intestinal Stem Cells<br/>Hematopoietic Stem Cells Form All Blood Cells and All Cells of the Immune System<br/>Characterizing Hematopoietic Stem Cells by Transplantation<br/>Niches for Hematopoietic Stem Cells and Many Hematopoietic Progenitor Cells<br/>Regulating the Production of Differentiated Hematopoietic Cells<br/>Meristems Are Niches for Stem Cells in Plants<br/>A Negative Feedback Loop Maintains the Size of the Shoot Apical Stem-Cell Population<br/>The Root Meristem Resembles the Shoot Meristem in Structure and Function<br/>22.3 Mechanisms of Cell Polarity and Asymmetric Cell Division<br/>The Intrinsic Polarity Program Depends on a Positive Feedback Loop Involving Cdc42<br/>Cell Polarization Before Cell Division Follows a Common Hierarchy of Steps<br/>Polarized Membrane Traffic Allows Yeast to Grow Asymmetrically During Mating<br/>The Par Proteins Direct Cell Asymmetry in the Nematode Embryo<br/>The Par Proteins and Other Polarity Complexes Are Involved in Epithelial-Cell Polarity<br/>The Planar Cell Polarity Pathway Orients Cells Within an Epithelium<br/>The Par Proteins Are Involved in Asymmetric Division of Stem Cells<br/>22.4 Cell Death and Its Regulation<br/>Most Programmed Cell Death Occurs Through Apoptosis<br/>Evolutionarily Conserved Proteins Participate in the Apoptotic Pathway<br/>Caspases Amplify the Initial Apoptotic Signal and Destroy Key Cellular Proteins<br/>Phosphatidylserine: an “Eat Me” Signal on the Surface of Apoptotic Cells<br/>Neurotrophins Promote Survival of Neurons<br/>Mitochondria Play a Central Role in Regulation of Apoptosis in Vertebrate Cells<br/>The Pro-Apoptotic Proteins Bax and Bak Form Pores and Holes in the Outer Mitochondrial Membrane<br/>Release of SMAC/DIABLO Proteins from Mitochondria Also Promotes Caspase Activation<br/>Trophic Factors Induce Inactivation of Bad, a Pro-apoptotic BH3-Only Protein<br/>Apoptosis in Vertebrates Is Induced by BH3-Only Pro-apoptotic Proteins That Are Activated by Environmental Stresses<br/>Apoptosis and Necroptosis Can Be Triggered by Tumor Necrosis Factor, Fas Ligand, and Related Death Proteins<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 23 Cells of the Nervous System<br/>23.1 Neurons and Glia: Building Blocks of the Nervous System<br/>Information Flows Through Neurons from Dendrites to Axons<br/>Information Moves Along Axons as Pulses of Ion Flow Called Action Potentials<br/>Information Flows Between Neurons via Synapses<br/>The Nervous System Uses Signaling Circuits Composed of Multiple Types of Neurons<br/>Glial Cells Form Myelin Sheaths and Support Neurons<br/>Neural Stem Cells Form Nerve and Glial Cells in the Central Nervous System<br/>23.2 Voltage-Gated Ion Channels and the Propagation of Action Potentials<br/>The Magnitude of the Action Potential Is Close to ENa and Is Caused by Na+ Influx Through Open Na+ Channels<br/>Sequential Opening and Closing of Voltage-Gated Na+ and K+ Channels Generate Action Potentials<br/>Action Potentials Are Propagated Unidirectionally Without Diminution<br/>All Voltage-Gated Ion Channels Have Similar Structures<br/>Voltage-Sensing S4 α Helices Move in Response to Membrane Depolarization<br/>Movement of the Channel-Inactivating Segment into the Open Pore Blocks Ion Flow<br/>Myelination Increases the Velocity of Impulse Conduction<br/>Action Potentials “Jump” from Node to Node in Myelinated Axons<br/>Two Types of Glia Produce Myelin Sheaths<br/>Light-Activated Ion Channels and Optogenetics<br/>23.3 Communication at Synapses<br/>Formation of Synapses Requires Assembly of Presynaptic and Postsynaptic Structures<br/>Neurotransmitters Are Transported into Synaptic Vesicles by H+-Linked Antiport Proteins<br/>Three Pools of Synaptic Vesicles Loaded with Neurotransmitter Are Present in the Presynaptic Terminal<br/>Influx of Ca2+ Triggers Release of Neurotransmitters<br/>A Calcium-Binding Protein Regulates Fusion of Synaptic Vesicles with the Plasma Membrane<br/>Fly Mutants Lacking Dynamin Cannot Recycle Synaptic Vesicles<br/>Signaling at Synapses Is Terminated by Degradation or Reuptake of Neurotransmitters<br/>Opening of Acetylcholine-Gated Cation Channels Leads to Muscle Contraction<br/>All Five Subunits in the Nicotinic Acetylcholine Receptor Contribute to the Ion Channel<br/>Nerve Cells Integrate Many Inputs to Make an All-or-None Decision to Generate an Action Potential<br/>Gap Junctions Allow Direct Communication Between Neurons and Between Glia<br/>23.4 Sensing the Environment: Touch, Pain, Taste, and Smell<br/>Mechanoreceptors Are Gated Cation Channels<br/>Pain Receptors Are Also Gated Cation Channels<br/>Five Primary Tastes Are Sensed by Subsets of Cells in Each Taste Bud<br/>The Largest Group of G Protein–Coupled Receptors Detect Odors<br/>Each Olfactory Receptor Neuron Expresses a Single Type of Odorant Receptor<br/>23.5 Forming and Storing Memories<br/>Memories Are Formed by Changing the Number or Strength of Synapses Between Neurons<br/>The Hippocampus Is Required for Memory Formation<br/>Multiple Molecular Mechanisms Contribute to Synaptic Plasticity<br/>Formation of Long-Term Memories Requires Gene Expression<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 24 Immunology<br/>24.1 Overview of Host Defenses<br/>Pathogens Enter the Body Through Different Routes and Replicate at Different Sites<br/>Cells of the Innate and Adaptive Immune Systems Circulate Throughout the Body and Take Up Residence in Tissues and Lymph Nodes<br/>Mechanical and Chemical Boundaries Form a First Layer of Defense Against Pathogens<br/>Innate Immunity Provides a Second Line of Defense<br/>Inflammation Is a Complex Response to Injury That Encompasses Both Innate and Adaptive Immunity and Helps Destroy Pathogens<br/>Adaptive Immunity, the Third Line of Defense, Exhibits Specificity<br/>24.2 Immunoglobulins: Structure and Function<br/>Immunoglobulins Have a Conserved Structure Consisting of Heavy and Light Chains<br/>Multiple Immunoglobulin Isotypes Exist, Each with Different Functions<br/>Each Naive B Cell Produces a Unique Immunoglobulin<br/>Immunoglobulin Domains Have a Characteristic Fold Composed of Two β Sheets Stabilized by a Disulfide Bond<br/>An Immunoglobulin’s Constant Region Determines Its Functional Properties<br/>24.3 Generation of Antibody Diversity and B-Cell Development<br/>A Functional Light-Chain Gene Requires Assembly of V and J Gene Segments<br/>Rearrangement of the Heavy-Chain Locus Involves V, D, and J Gene Segments<br/>Somatic Hypermutation Allows the Generation and Selection of Antibodies with Improved Affinities<br/>B-Cell Development Requires Input from a Pre-B-Cell Receptor<br/>During an Adaptive Response, B Cells Switch from Making Membrane-Bound Ig to Making Secreted Ig<br/>B Cells Can Switch the Isotype of Immunoglobulin They Make<br/>24.4 The MHC and Antigen Presentation<br/>The MHC Determines the Ability of Two Unrelated Individuals of the Same Species to Accept or Reject Grafts<br/>The Killing Activity of Cytotoxic T Cells Is Antigen Specific and MHC Restricted<br/>T Cells with Different Functional Properties Are Guided by Two Distinct Classes of MHC Molecules<br/>MHC Molecules Are Highly Polymorphic, Bind Peptide Antigens, and Interact with the T-Cell Receptor<br/>In Antigen Presentation, Protein Fragments Are Complexed with MHC Products and Posted to the Cell Surface<br/>The Class I MHC Pathway Presents Cytosolic Antigens<br/>The Class II MHC Pathway Presents Antigens Delivered to the Endocytic Pathway<br/>24.5 T Cells, T-Cell Receptors, and T-Cell Development<br/>The Structure of the T-Cell Receptor Resembles the F(ab) Portion of an Immunoglobulin<br/>TCR Genes Are Rearranged in a Manner Similar to Immunoglobulin Genes<br/>Many of the Variable Residues of TCRs Are Encoded in the Junctions Between V, D, and J Gene Segments<br/>Signaling via Antigen-Specific Receptors Triggers Proliferation and Differentiation of T and B Cells<br/>T Cells Capable of Recognizing MHC Molecules Develop Through a Process of Positive and Negative Selection<br/>T Cells Commit to the CD4 or CD8 Lineage in the Thymus<br/>T Cells Require Two Types of Signals for Full Activation<br/>Cytotoxic T Cells Carry the CD8 Co-Receptor and Are Specialized for Killing<br/>T Cells Secrete an Array of Cytokines That Provide Signals to Other Immune-System Cells<br/>Helper T Cells Are Divided into Distinct Subsets Based on Their Cytokine Production and Expression of Surface Markers<br/>Innate Lymphoid Cells Regulate Inflammation and the Overall Immune Response<br/>Leukocytes Move in Response to Chemotactic Cues Provided by Chemokines<br/>24.6 Collaboration of Immune-System Cells in the Adaptive Response<br/>Toll-Like Receptors Perceive a Variety of Pathogen-Derived Macromolecular Patterns<br/>Engagement of Toll-Like Receptors Leads to Activation of Antigen-Presenting Cells<br/>Production of High-Affinity Antibodies Requires Collaboration Between B and T cells<br/>Vaccines Elicit Protective Immunity Against a Variety of Pathogens<br/>The Immune System Defends Against Cancer<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Chapter 25 Cancer<br/>25.1 How Tumor Cells Differ from Normal Cells<br/>The Genetic Makeup of Most Cancer Cells Is Dramatically Altered<br/>Uncontrolled Proliferation Is a Universal Trait of Cancer<br/>Cellular Housekeeping Functions Are Fundamentally Altered in Cancer Cells<br/>Cancer Cells Exhibit Altered Cell-Cell Interactions to Form Heterogeneous Organs<br/>Tumor Growth Requires Formation of New Blood Vessels<br/>Invasion and Metastasis Are Late Stages of Tumorigenesis<br/>25.2 Genetic and Genomic Basis of Cancer<br/>Carcinogens Induce Cancer by Damaging DNA<br/>Some Carcinogens Have Been Linked to Specific Cancers<br/>Familial Syndromes That Cause Loss of DNA Repair Can Lead to Cancer<br/>Somatic Mutations in the DNA Damage Response Pathway Are Oncogenic<br/>Cancer Genome Sequencing Reveals an Enormous Diversity of Somatic Mutations<br/>Oncogenes Were Discovered by Their Association with Tumor Viruses<br/>Single Oncogenic Drivers Can Be Activated by Chromosome Rearrangements<br/>Inherited Predisposition for Cancer Enabled Identification of Some Oncogenic Drivers<br/>Oncogenic Driver Mutations Have Been Identified in Many Genes<br/>Oncogenic Driver Mutations Can Be Identified by Comparing Cancer Genomes<br/>Oncogenic Drivers Can Be Gain-of-Function or Loss-of-Function Mutations<br/>Tumor Suppressor Genes and Oncogenes Often Operate in the Same Pathway<br/>MicroRNAs Can Promote and Inhibit Tumorigenesis<br/>Epigenetic Changes Can Contribute to Tumorigenesis<br/>25.3 Dysregulation of Cell Growth and Developmental Pathways Initiates Tumorigenesis<br/>Receptor Mutations Can Cause Proliferation in the Absence of External Growth Factors<br/>Many Oncogenic Mutations Constitutively Activate Signal-Transducing Proteins<br/>Growth Control Pathways Ultimately Regulate Initiation of the Cell Cycle<br/>Inappropriate Production of Nuclear Transcription Factors Can Induce Transformation<br/>Aberrations in Signaling Pathways That Control Development Are Associated with Many Cancers<br/>Experimental Reconstruction of the Multi-Hit Model for Cancer<br/>The Succession of Oncogenic Mutations Can Be Traced in Colon Cancers<br/>Cancer Development Can Be Studied in Animal Models<br/>Molecular Cell Biology Is Changing How Cancer Is Diagnosed and Treated<br/>25.4 Evasion of Programmed Cell Death and Immune Surveillance Processes<br/>Oncogenic Driver Mutations Enable Cancer Cells to Evade Apoptosis<br/>p53 Can Activate Either the DNA Damage Checkpoint or Apoptosis in Response to DNA Damage<br/>The Immune System Is a Second Line of Defense Against Cancer Formation<br/>The Tumor Microenvironment and Immunoediting Limit the Ability of the Immune System to Detect and Kill Established Tumors<br/>Activation of the Immune System Presents a Major Opening for Cancer Therapy<br/>End of Chapter<br/>Key Terms<br/>Review the Concepts<br/>Index<br/>Glossary (online and e-book only)<br/>References (online and e-book only)<br/>Back Cover<br/> |
