Includes bibliographical references and index.

About this Book
Cover Page
Halftitle Page
Title Page
Copyright Page
Dedication
About the Authors
Visual Preface
Preface
Acknowledgments
Brief Contents
Contents
Chapter 1 Evolution: Molecules, Genes, Cells, and Organisms
1.1 The 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
Quality Control of All Cellular Macromolecules Is Essential for Life
1.2 Prokaryotic Cell Structure and Function
Prokaryotes Comprise Two Kingdoms: Archaea and Eubacteria
Many Bacteria Including Escherichia coli Are Widely Used in Biological Research
1.3 Eukaryotic Cell Structure and Function
The Cytoskeleton Has Many Important Functions
The Nucleus Contains the DNA Genome, Apparatuses for Synthesis of DNA and RNA, and a Fibrous Matrix
The Endoplasmic Reticulum Is the Site of Synthesis of Most Membrane and Secreted Proteins as Well as Many Lipids
The Golgi Complex Sorts Secreted Proteins and Many Membrane Proteins to Their Final Destinations in the Cell
Endosomes Bring Proteins and Particles from the Outside into Cells
Lysosomes Are Cellular Recycling Centers
Plant Vacuoles Store Water, Ions, and Small-Molecule Nutrients Such as Sugars and Amino Acids
Peroxisomes and Plant Glyoxisomes Metabolize Fatty Acids and Other Small Molecules Without Producing ATP from ADP and Pi
Mitochondria Are the Principal Sites of ATP Production in Aerobic Cells
Chloroplasts Contain Internal Compartments in Which Photosynthesis Takes Place
Many Organelle-Like Structures Are Unbounded by a Membrane
All Eukaryotic Cells Use a Similar Cycle to Regulate Their Division
1.4 Unicellular Eukaryotic Organisms Widely Used in Cell Biology Research
Yeasts Are Used to Study Fundamental Aspects of Eukaryotic Cell Structure and Function
Mutations in Yeast Led to the Identification of Key Cell Cycle Proteins
Studies in the Alga Chlamydomonas reinhardtii Led to the Development of a Powerful Technique to Study Brain Function
The Parasite That Causes Malaria Has Novel Organelles That Allow It to Undergo a Remarkable Life Cycle
1.5 Metazoan Structure, Function, Evolution, and Differentiation
Multicellularity Requires Cell-Cell and Cell-Matrix Adhesions
Epithelia Originated Early in Evolution
Cells Are Organized into Tissues and Tissues into Organs
Genomics Has Revealed Important Aspects of Metazoan Evolution and Cell Function
Development Uses a Conserved Set of Master Transcription Factors and Involves Epigenetic Modifications to DNA and Its Associated Histone Proteins
1.6 Metazoan Organisms Widely Used in Cell Biology Research
Drosophila melanogaster and Caenorhabditis elegans Are Used to Identify Genes That Regulate Animal Development
Planaria Are Used to Study Stem Cells and Tissue Regeneration
Studies on Fish, Mice, and Other Vertebrate Organisms Inform the Study of Human Development and Disease
Human Genetic Diseases Elucidate Important Aspects of Cell Function
Unbiased Single Cell Sequencing Experiments Identify Altogether New Cell Types
The Following Chapters Present Many Experimental Techniques and Much Experimental Data That Explains How We Know What We Know About Cell Structure and Function
Chapter 2 Chemical Foundations
2.1 Covalent Bonds and Noncovalent Interactions
The Electronic Structure of an Atom Determines the Number and Geometry of the Covalent Bonds It Can Make
All Covalent Bonds Are Not Equal: Electrons May Be Shared Equally or Unequally in Covalent Bonds
Covalent Bonds Are Much Stronger and More Stable Than Noncovalent Interactions
Ionic Bonds Are Noncovalent Interactions Formed by the Electrostatic Attractions Between Oppositely Charged Ions
Hydrogen Bonds Are Noncovalent Interactions That Determine the Properties of Water and the Water Solubility of Uncharged Molecules
Van der Waals Interactions Are Weak Attractive Interactions Caused by Transient Dipoles
The 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
A Chemical Reaction Is in Equilibrium When the Rates of the Forward and Reverse Reactions Are Equal
The 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
The Change in Free Energy Determines If a Chemical Reaction Will Occur Spontaneously
The ΔG°′ of a Reaction Can Be Calculated from Its Keq
The Rate of a Reaction Depends on the Activation Energy Necessary to Energize the Reactants into a Transition State
Life Depends on the Coupling of Energetically 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
End of Chapter
Key Terms
Review the Concepts
Chapter 3 Protein Structure and Function
3.1 Hierarchical Structure of Proteins
The Primary Structure of a Protein Is Its Linear Arrangement of Amino Acids
Secondary Structures Are the Core Elements of Protein Architecture
Structural Motifs Are Regular Combinations of Secondary Structures
Tertiary Structure Is the Overall Folding of a Polypeptide Chain
Different Ways of Depicting the Conformation of Proteins Convey Different Types of Information
Domains Are Modules of Tertiary Structure
Comparing Protein Sequences and Structures Provides Insight into Protein Function and Evolution
There Are Four Broad Structural Categories of Proteins
Multiple Polypeptides Assemble into Quaternary Structures, Supramolecular Complexes, and Biomolecular Condensates
3.2 Protein Folding
Planar Peptide Bonds Limit the Shapes into Which Proteins Can Fold
Protein Folding Is Promoted by Proline Isomerases
The Amino Acid Sequence of a Protein Determines How It Will Fold
Folding of Proteins In Vivo Is Promoted by Chaperones
Abnormally Folded Proteins Can Form Amyloids That 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
An 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
The 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
Covalent Modification of Proteins Can Regulate their Activities
Phosphorylation and Dephosphorylation Covalently Regulate Protein Activity
The Structure and Function of Protein Kinase A Is Typical of Many Kinases
Protein Kinase Activity Is Often Regulated by Phosphorylation of the Kinase
Ubiquitinylation and Deubiquitinylation Covalently Regulate Protein Activity
Proteolytic Cleavage Irreversibly Activates or Inactivates Some Proteins
Higher Order Regulation Includes Control of Protein Location
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 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
End of Chapter
Key Terms
Review the Concepts
Chapter 4 Culturing and Visualizing Cells
4.1 Growing and Studying 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
Stem Cells Can Differentiate in Culture to Make Organoids
Hybridomas Produce Abundant Monoclonal Antibodies
A Wide Variety of Cell Biological Processes Can Be Studied with Cultured Cells
Drugs Are Commonly Used in Cell Biological Research
4.2 Light Microscopy: Exploring Cell Structure and Visualizing Proteins Within Cells
The Resolution of the Conventional Light Microscope Is About 0.2 μm
Phase-Contrast and Differential-Interference-Contrast Microscopy Visualize Unstained Live Cells
Imaging Subcellular Details Often Requires That Specimens Be Fixed, Sectioned, and Stained
Fluorescence Microscopy Can Localize and Quantify Specific Molecules in Live Cells
Intracellular Ion Concentrations Can Be Determined 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 Live Cells
Deconvolution and Confocal Microscopy Enhance Visualization of Three-Dimensional Fluorescent Objects
Two-Photon Excitation Microscopy Allows Imaging Deep into Tissue Samples
TIRF Microscopy Provides Exceptional Imaging in One Focal Plane
FRAP Reveals the Dynamics of Cellular Components
FRET Measures Distance Between Fluorochromes
Optogenetics Allows Light to Regulate Events in a Spatial and Temporal Manner
Point Source Fluorescent Objects Can Be Located at Nanometer Resolution
Super-Resolution Microscopy Can Localize Proteins to Nanometer Accuracy
Light-Sheet Microscopy Can Rapidly Image Cells in Living Tissue
4.3 Electron Microscopy: High-Resolution Imaging
Single Molecules or Structures Can Be Imaged Using 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
4.4 Isolation of Cell Organelles
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
End of Chapter
Key Terms
Review the Concepts
Chapter 5 Fundamental Molecular Genetic Mechanisms
5.1 The Double-Helical Structure of DNA
Native DNA Is a Double Helix of Complementary Antiparallel Strands
DNA Can Undergo Reversible Strand Separation
DNA Molecules Can Acquire Torsional Stress
5.2 DNA Replication
DNA Polymerases Require a Template and a Primer to Replicate DNA
Duplex DNA Is Unwound, and Daughter Strands Are Formed at the DNA Replication Fork
A DNA Replication Fork Advances by Cooperation of Multiple Proteins
DNA Replication Occurs Bidirectionally from Each Origin
5.3 DNA Repair and Recombination
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 Use Recombination to Repair Double-Strand Breaks in DNA
Homologous Recombination Can Repair DNA Damage and Generate Genetic Diversity
5.4 Transcription of Protein-Coding Genes and Formation of mRNA
A Template DNA Strand Is Transcribed into a Complementary RNA Strand by RNA Polymerase
Eukaryotic Precursor mRNAs Are Processed to Form Functional mRNAs
Alternative RNA Splicing Increases the Number of Proteins That Can Be Expressed from a Single Eukaryotic Gene
5.5 The Decoding of mRNA by tRNAs
Messenger RNA Carries Information from DNA in a Three-Letter Genetic Code
The Folded Structure of tRNA Promotes Its Decoding Functions
Nonstandard Base Pairing Often Occurs Between Codons and Anticodons
Amino Acids Are Linked to Their Cognate tRNAs with Great Accuracy
5.6 Stepwise Synthesis of Proteins on Ribosomes
Ribosomes Are Protein-Synthesizing Machines
Methionyl-tRNAiMet Recognizes the AUG Start Codon
Eukaryotic Translation Initiation Usually Occurs at the First AUG Downstream from 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 Can Be Bypassed by Suppressing tRNA Mutations
5.7 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
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
End of Chapter
Key Terms
Review the Concepts
Chapter 6 Molecular Genetic Techniques
6.1 Using 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 Whether They Are Dominant or Recessive
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
Global Analysis of Double Mutant Combinations Can Reveal Networks of Gene Functions
6.2 DNA Cloning and Characterization
Restriction Enzymes and DNA Ligases Allow Insertion of DNA Fragments into Cloning Vectors
Isolated DNA Fragments Can Be Cloned into E. coli Plasmid Vectors
Yeast Genomic Libraries Can Be Constructed with Shuttle Vectors and Screened by Functional Complementation
cDNA Libraries Represent the Sequences of Protein-Coding Genes
The Polymerase Chain Reaction Amplifies a Specific DNA Sequence from a Complex Mixture
Cloned DNA Molecules Can Be Sequenced Rapidly by Methods Based on PCR
6.3 Using Sequence Information to Identify Genes and Deduce Their Function
Most Genes Can Be Readily Identified Within Genomic DNA Sequences
Bioinformatic Principles Can Be Used to Deduce the Likely Functional Consequences of Mutations
The Function and Evolutionary Origins of Genes and Proteins Can Be Deduced from Their Sequence
Comparison of Related Sequences from Different Species Can Give Clues to Evolutionary Relationships Among Proteins
Biological Complexity of an Organism Is Not Directly Related to the Number of Protein-Coding Genes in the Genome
6.4 Locating and Identifying Genes That Specify Human Traits
Monogenic Diseases Show One of Three Patterns of Inheritance
DNA Polymorphisms Are Used as Markers for Linkage Mapping of Human Mutations
Human Linkage Studies Can Map Disease Genes with a Resolution of About 1 Mbp
Further Analysis Is Needed to Locate a Disease Gene in Cloned DNA
Most Inherited Diseases Result from Multiple Genetic Defects
Identifying Component Genetic Risk Factors of Complex Traits
Medically Important Genes Can Be Identified by Alleles That Protect Against Disease
Identification of Causative Mutations in Cancer Cells
6.5 Using Cloned DNA Fragments to Study Gene Expression
In Situ Hybridization Techniques Permit Detection of Specific mRNAs
DNA Microarrays Can Be Used to Evaluate the Expression of Many Genes at Once
Cluster Analysis of Multiple Expression Experiments Identifies Co-Regulated Genes
Sequencing of cDNAs Allows Analysis of Gene Expression in Individual Cells
E. coli Expression Systems Can Produce Large Quantities of Proteins from Cloned Genes
Plasmid Expression Vectors Can Be Designed for Use in Animal Cells
6.6 Altering the Function of Specific Genes by Design
Normal Yeast Genes Can Be Replaced with Mutant Alleles by Homologous Recombination
Engineered CRISPR Systems Allow Precise Genome Editing
Somatic Cell Recombination Can Inactivate Genes in Specific Tissues of Mice
RNA Interference Causes Gene Inactivation by Destroying the Corresponding mRNA
End of Chapter
Key Terms
Review the Concepts
Chapter 7 Genes, Chromatin, and Chromosomes
7.1 Eukaryotic Gene Structure and Organization
Most Genes of Multicellular Eukaryotes 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
7.2 Chromosomal Organization of Genes and Noncoding DNA
Genomes of Many Organisms Contain a Large Fraction of Noncoding DNA
Most Simple-Sequence DNAs Are Concentrated in Specific Chromosomal Locations
DNA Fingerprinting Depends on Differences in Length of Simple-Sequence DNAs
Unclassified Intergenic DNA Occupies a Significant Portion of the Genome
7.3 Transposable (Mobile) DNA Elements
Movement of Mobile Elements Involves a DNA or an RNA Intermediate
Most Mobile Elements in Bacteria Are DNA Transposons Known as Insertion Sequences
Eukaryotic DNA Transposons Move Using a Cut-and-Paste Process
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
7.4 Structural Organization of Eukaryotic Chromatin and Chromosomes
Chromatin Structure
Chromatin Structure Is Conserved Among Eukaryotes
Chromatin Is a Disordered Chain of Nucleosomes Packed Together at Different Concentration Densities in the Nucleus
Modifications of Histone Tails Control Chromatin Condensation and Function
Additional Nonhistone Proteins Regulate Transcription and Replication
7.5 Morphology and Functional Elements of Eukaryotic Chromosomes
Chromosome Number, Size, and Shape at Metaphase Are Species-Specific
During Metaphase, Chromosomes Can Be Distinguished by Banding Patterns and Chromosome Painting
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
End of Chapter
Key Terms
Review the Concepts
Chapter 8 Transcriptional Control of Gene Expression
8.1 Overview of Eukaryotic Transcription
Regulatory Elements in Eukaryotic DNA Are Found Both Close to and Many Kilobases Away from Transcription Start Sites
Three Eukaryotic Nuclear RNA Polymerases Catalyze Formation of Different RNAs
The Clamp Domain Enables RNA Polymerase II to Transcribe Long Stretches of DNA
The Largest Subunit in RNA Polymerase II Has an Essential Carboxy-Terminal Repeat
8.2 RNA Polymerase II Promoters and General Transcription Factors
RNA Polymerase II Initiates Transcription at DNA Sequences Corresponding to the 5′ Cap of mRNAs
The TATA Box, Initiators, and CpG Islands Function as Promoters in Eukaryotic DNA
General Transcription Factors Position RNA Polymerase II at Transcription Start Sites and Assist in Initiation
Elongation Factors Regulate the Initial Stages of Transcription in the Promoter-Proximal Region
8.3 Regulatory Sequences for 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
DNase I Footprinting and EMSA Detect Protein-DNA Interactions
Activators Are Composed of Distinct Functional Domains
Repressors 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
8.4 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 Complexes Help Activate or Repress Transcription
Pioneer Transcription Factors Initiate the Process of Gene Activation During Cellular Differentiation
The Mediator Complex Forms a Molecular Bridge Between Activation Domains and Pol II
Transcriptional Condensates Greatly Increase the Rate of Transcription Initiation
Transcription Occurs in Bursts
8.5 Regulation of Transcription-Factor Activity
DNase I Hypersensitive Sites Reflect the Developmental History of Cellular Differentiation
Nuclear Receptors Are Regulated by Lipid-Soluble Hormones
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
Metazoans Regulate the RNA Polymerase II Transition from Initiation to Elongation
Termination of Transcription Is Also Regulated
8.6 Epigenetic Regulation of Transcription
DNA Methylation Regulates Transcription
Methylation of Specific Histone Lysines Is Linked to Epigenetic Mechanisms of Gene Repression
Epigenetic Control by Polycomb and Trithorax Complexes
Long Noncoding RNAs Direct Epigenetic Repression in Metazoans
8.7 Other Eukaryotic Transcription Systems
Transcription Initiation by Pol I and Pol III Is Analogous to That by Pol II
End of Chapter
Key Terms
Review the Concepts
Chapter 9 Post-Transcriptional Gene Control
9.1 Processing of Eukaryotic Pre-mRNA
The 5′ Cap Is Added to Nascent RNAs Shortly After Transcription Initiation
Chain Elongation by RNA Polymerase II Is Coupled to the Presence of RNA Processing Factors
A 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 to Select Splice Sites and Guide the Transesterification Reactions
Spliceosomes Catalyze Pre-mRNA Splicing
3′ Cleavage and Polyadenylation of Pre-mRNAs Are Tightly Coupled
9.2 Regulation of Pre-mRNA Processing
Additional Nuclear Proteins Contribute to Splice-Site Selection in the Long Pre-mRNAs of Humans and Other Vertebrates
Expression and Function of Related K+-Channel Protein Isoforms in Vertebrate Inner Ear Hair Cells
Regulation of RNA Splicing Through Splicing Enhancers and Silencers Controls Drosophila Sexual Differentiation
Splicing Repressors and Activators Control Splicing at Alternative Sites
Expression of Dscam Isoforms in Drosophila Retinal Neurons
Abnormal RNA Splicing and Disease
Self-Splicing Group II Introns Provide Clues to the Evolution of snRNAs
Nuclear Exonucleases and the Exosome Degrade RNA That Is Processed out of Pre-mRNAs
RNA Processing Solves the Problem of Pervasive Transcription of the Genome in Mammalian Cells
RNA Editing Alters the Sequences of Some Pre-mRNAs
9.3 Transport of mRNA Across the Nuclear Envelope
SR Proteins Mediate Nuclear Export of mRNA
Pre-mRNAs Associated with Spliceosomes Are Not Exported from the Nucleus
HIV Rev Protein Regulates the Transport of Unspliced Viral mRNAs
9.4 Cytoplasmic Mechanisms of Post-Transcriptional Control
The Concentration of an mRNA in the Cytoplasm Is Determined by Its Rate of Synthesis and Its Rate of Degradation
Degradation of mRNAs in the Cytoplasm Occurs by Several Mechanisms
MicroRNAs Repress Translation and Induce Degradation of Specific mRNAs
RNA Interference Induces Degradation of Precisely Complementary mRNAs
Cytoplasmic Polyadenylation Promotes Translation of Some mRNAs
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
9.5 Processing of rRNA and tRNA
Pre-rRNA Genes Are Similar in All Eukaryotes and Function as Nucleolar Organizers
Small Nucleolar RNAs Assist in Processing Pre-rRNAs
Self-Splicing Group I Introns Were the First Examples of Catalytic RNA
Pre-tRNAs Undergo Extensive Modification in the Nucleus
9.6 Nuclear Bodies Are Functionally Specialized Nuclear Domains
Cajal Bodies
Nuclear Speckles
Nuclear Paraspeckles
Promyelocytic Leukemia (PML) Nuclear Bodies
Nucleolar Functions in Addition to Ribosomal Subunit Synthesis
End of Chapter
Key Terms
Review the Concepts
Chapter 10 Biomembrane Structure
10.1 The 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 Cytosol and ER Membrane
Cholesterol and Phospholipids Are Transported Between Organelles by Several Mechanisms
End of Chapter
Key Terms
Review the Concepts
Chapter 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 Cellular Membranes
11.2 Facilitated Transport of Glucose and Water
Uniport Transport Is Faster and More Specific than Simple Diffusion
The Low Km of the GLUT1 Uniporter Enables It to Transport Glucose into Most Mammalian Cells
The 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 Cellular 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
The Mechanism of Action of the Ca2+ Pump Is Known in Detail
The 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
The ABC Cystic Fibrosis Transmembrane Regulator 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
The Resting Membrane Potential in Animal Cells Depends Largely on the Outward Flow of K+ Ions Through Open K+ Channels
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 Sugars Including Glucose and Galactose as Well as Amino Acids Against High Concentration Gradients
A Bacterial Na+/Amino Acid Symporter Reveals How Symport Works
A Na+-Linked Ca2+ Antiporter Regulates the Strength of Cardiac Muscle Contraction
Several Cotransporters Regulate Cytosolic pH
An Anion Antiporter Is Essential for Transport of CO2 by Erythrocytes
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 Resorption Requires the Coordinated Function of a V-Class Proton Pump and a Specific Chloride Channel
End of Chapter
Key Terms
Review the Concepts
Chapter 12 Cellular Energetics
12.1 Chemiosmosis, Electron Transport, the Proton-Motive Force, and ATP Synthesis
12.2 First Step of Harvesting Energy from Glucose: Glycolysis
During Glycolysis (Stage I), Cytosolic Enzymes Convert Glucose to Pyruvate
The Rate of Glycolysis Is Adjusted to Meet the Cell’s Need for ATP
Glucose Is Fermented When Oxygen Is Scarce
12.3 The Structure of Mitochondria
Mitochondria Are Abundant, Multifunctional Organelles
Mitochondria Have Two Structurally and Functionally Distinct Membranes
Mitochondria Contain DNA and Evolved from a Single Endosymbiotic Event Involving Alphaproteobacterium
The Size, Structure, and Coding Capacity of mtDNA Vary Considerably Among Organisms
Mitochondrial DNA Is Located in the Matrix and Transferred During Mitosis to Daughter Cells by Cytoplasmic Inheritance
Products of Mitochondrial Genes Are Not Exported
Mitochondrial Genetic Codes Can Differ from the Standard Nuclear Code
Mutations in Mitochondrial DNA Cause Several Genetic Diseases in Humans
12.4 The Dynamics of Mitochondria and Mitochondrial-ER Membrane Contact Sites
Mitochondria Are Dynamic Organelles
Mitochondrial Function and Dynamics Can Depend on Direct Contacts with Other Organelles
12.5 The Citric Acid Cycle and Fatty Acid Oxidation
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
12.6 The Electron-Transport Chain and Generation of the Proton-Motive Force
Oxidation of NADH and FADH2 Releases a Substantial Amount of Energy
Electron Transport in Mitochondria Is Coupled to Proton Pumping
Electrons Release Energy as They Flow Downhill Through a Series of Electron Carriers
Four Large Multiprotein Complexes (I–IV) Couple Electron Transport to Proton Pumping Across the Inner Mitochondrial Membrane
The Reduction Potentials of Electron Carriers in the Electron-Transport Chain Favor Electron Flow from NADH to O2
The Multiprotein Complexes of the Electron-Transport Chain Assemble into Supercomplexes
Reactive Oxygen Species Are By-Products of Electron Transport
Experiments Using Purified Electron-Transport Chain Complexes Established the Stoichiometry of Proton Pumping
The Proton-Motive Force in Mitochondria Is Due Largely to a Voltage Gradient Across the Inner Membrane
12.7 Harnessing the Proton-Motive Force to Synthesize ATP
The Mechanism of ATP Synthesis Is Shared Among Bacteria, Mitochondria, and Chloroplasts
ATP Synthase Comprises F0 and F1 Multiprotein Complexes
Rotation of the F1γ 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 and Phosphate Transport Across the Inner Mitochondrial Membrane Are Required to Supply ADP and Phosphate for ATP Synthesis
The Rate of Mitochondrial Oxidation Normally Depends on ADP Levels
Mitochondria in Brown Fat Use the Proton-Motive Force to Generate Heat
12.8 Chloroplasts and Photosynthesis
Thylakoid Membranes in Chloroplasts Are the Sites of Photosynthesis in Plants
Chloroplasts Contain Large DNAs Often Encoding More Than a Hundred Proteins
Light Absorption by Photosystems in Chloroplasts Provides the Energy That Drives the Synthesis of NADPH and ATP and the Generation of O2 from H2O
Three of the Four Stages in Photosynthesis Occur on the Thylakoid Membrane and Only During Illumination
Stages 1 and 2 of Photosynthesis Convert Sunlight into High Energy Electrons That Generate a Proton-Motive Force and NADPH
Core Antenna Complexes and Light-Harvesting Complexes Increase the Efficiency of Photosynthesis
Multiple Mechanisms Protect Cells Against Damage from Reactive Oxygen Species During Photoelectron Transport
12.9 Use of Light Energy to Generate Molecular Oxygen, NADPH, and ATP in Stages 1–3 of Photosynthesis
The First Three Stages of Photosynthesis
Relative Activities of Photosystems I and II Are Regulated
12.10 ATP and NADPH Drive Carbon Fixation in the Calvin Cycle and Carbohydrate Synthesis in Stage 4 of Photosynthesis
Rubisco Fixes CO2 in the Chloroplast Stroma
Photorespiration Competes with Carbon Fixation and Is Reduced in C4 Plants
End of Chapter
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Review the Concepts
Chapter 13 Moving Proteins into Membranes and Organelles
13.1 Targeting Proteins to and Across the ER Membrane
Pulse-Chase Experiments with Purified ER Membranes Demonstrated That Secreted Proteins Cross the ER Membrane
A 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 Anchor and Signal-Anchor Sequences Determine Topology of Single-Pass Proteins
Type IV (Multipass) Proteins
A Phospholipid Anchor Tethers Some Cell-Surface Proteins to the Membrane
The Topology of a Membrane Protein Can Often Be Deduced from Its Sequence
13.3 Protein Modifications, Folding, and Quality Control in the ER
A 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 Targeting 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 Protein Import
Three Energy Inputs Are Needed to Import Proteins into Mitochondria
Multiple Signals and Pathways Target Proteins to Submitochondrial Compartments
Import of Chloroplast Stromal Proteins Is Similar to Import of Mitochondrial Matrix Proteins
Proteins Are Targeted to Thylakoids by Mechanisms Related to Bacterial Protein Translocation
13.5 Targeting of Peroxisomal Proteins
A Cytosolic Receptor Targets Proteins with an SKL Sequence at the C-Terminus to 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
A Second Type of Nuclear Transport Receptor Escorts Proteins Containing Nuclear-Export Signals out of the Nucleus
Most mRNAs Are Exported from the Nucleus by a Ran-Independent Mechanism
End of Chapter
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Review the Concepts
Chapter 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 Live Cells
Yeast Mutants Define Major Stages and Components of 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
A Conserved Set of GTPase Switch Proteins Controls the 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 Adapter Proteins Mediate Transport from the trans-Golgi
Dynamin Is Required for Pinching Off of Clathrin-Coated Vesicles
Mannose 6-Phosphate Residues Target Resident Enzymes 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
Distinct 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 Macromolecular Ligands Contain Sorting Signals That Target Them for Endocytosis
The Acidic pH of Late Endosomes Causes Most Receptor-Ligand Complexes to Dissociate
Receptor-Mediated Endocytosis Can Down-Regulate Signaling Receptors
14.6 Directing Membrane Proteins and Cytosolic Materials to the Lysosome for Degradation
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
The Autophagic Pathway Delivers Cytosolic Proteins or Entire Organelles to Lysosomes
End of Chapter
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Review the Concepts
Chapter 15 Receptors, Hormones, and Cell Signaling
15.1 Signal Transduction Pathways: From Extracellular Signal to Cellular Response
Signaling Molecules Can Act Locally or at a Distance
Signal Transduction Pathways Can Produce Rapid, Short-Term or Slow, Long-Term Changes in Cells, or Both
Receptors Are Allosteric Proteins That Activate Signal Transduction Pathways
Receptors Can Be in the Cytosol, Nucleus, or on the Cell Surface Membrane
Most Receptors Bind Only a Single Type of Ligand or a Group of Closely Related Ligands
Most Receptors Bind Their Ligands with High Affinity
Second Messengers Are Used in Most Signal Transduction Pathways
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
GTP-Binding Proteins Are Frequently Used in Signal Transduction Pathways as On/Off Switches
Signal Amplification and Feedback Repression Characterize Most Signal Transduction Pathways
15.2 Studying Cell-Surface Receptors and Signal Transduction Proteins
Binding Assays Are Used to Detect Receptors and Determine Their Affinity and Specificity for Ligands
Near-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 Cell-Surface Receptors and Their Affinity for Ligand
Chemical Analogs of Signaling Molecules Are Used to Study Receptors and Are Widely Used as Drugs
Receptors Can Be Purified by Affinity Chromatography Techniques
Immunoprecipitation Assays and Affinity Techniques Can Be Used to Study the Activity of Protein Kinases
Immunoprecipitation of Kinases
Western Blotting with a Monoclonal Antibody Specific for a Phosphorylated Amino Acid in a Protein
GTP-Binding Signal Transduction Proteins Can Be Isolated and Their Activities Measured Using Pull-Down Assays
Concentrations of Free Ca2+ in the Mitochondrial Matrix, ER, and Cytosol Can Be Measured with Targeted Fluorescent Proteins
15.3 Structure and Mechanism of G Protein–Coupled Receptors
All G Protein–Coupled Receptors Share the Same Basic Structure
Ligand-Activated G Protein–Coupled Receptors Catalyze Exchange of GTP for GDP on the α Subunit of a Heterotrimeric G Protein
Different G Proteins Are Activated by Different GPCRs and in Turn Regulate Different Effector Proteins
Analysis of GPCRs Has Identified Important Human Hormones
15.4 Regulating Metabolism of Many Cells: G Protein–Coupled Receptors That Activate or Inhibit Adenylyl Cyclase
Adenylyl Cyclase Is Stimulated and Inhibited by Different Receptor-Ligand Complexes
cAMP Activates Protein Kinase A by Releasing Its Inhibitory Subunits
Glycogen Catabolism Is Stimulated by Hormone-Induced Activation of PKA
Signal Amplification Occurs in the cAMP-PKA Glycogen Degradation Pathway
cAMP-Mediated Activation of PKA Produces Diverse Responses in Different Cell Types
CREB Links cAMP and PKA to Activation of Gene Transcription
Anchoring Proteins Localize Effects of cAMP to Specific Regions of the Cell
Multiple Feedback Mechanisms Suppress Signaling by the GPCR/cAMP/PKA Pathway
15.5 Regulating Protein Secretion and Muscle Contraction: Ca2+ Ions as Second Messengers in Multiple Signal Transduction Pathways
Products of the Hydrolysis of the Membrane Lipid Phosphatidylinositol 4,5-Bisphosphate by Phospholipase C Elevate Cytosolic Ca2+ Levels
Ca2+ Release from the ER Triggered by IP3
IP3-triggered Ca2+ Transport from the ER to the Mitochondrial Matrix
The Store-Operated Ca2+ Channel in the Plasma Membrane
Feedback Loops in ER and Cytosol Cycling of Ca2+ Trigger Oscillations in the Cytosolic Ca2+ Concentration
DAG Activates Protein Kinase C
Integration of Ca2+ and cAMP Second Messengers Regulates Glycogenolysis
15.6 Vision: How the Eye Senses Light
Light Activates Rhodopsin 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 the Temporal Resolution of Vision
Termination of the Signal from Light-Activated Rhodopsin (R*) by Rhodopsin Phosphorylation and Binding of Arrestin
Termination of the Signal from Activated Gαt ⋅ GTP by GTP Hydrolysis
Rod Cells Adapt to Varying Levels of Ambient Light by Intracellular Trafficking of Arrestin and Transducin
End of Chapter
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Review the Concepts
Chapter 16 Growth Factor and Cytokine Signaling Pathways That Control Gene Expression
16.1 Growth Factors and Their Receptor Tyrosine Kinases
Binding of Ligand to the Extracellular Domain of an RTK Leads to Dimerization and Activation of Its Intrinsic Cytosolic Tyrosine Kinase
Homo- and Hetero-Oligomers of Epidermal Growth Factor Receptors Bind Members of the Epidermal Growth Factor Family
EGF Receptor Homodimers
EGF Receptor Heterodimers with HER2
Ligand Binding to the EGF Receptor and Receptor Dimerization Results in the Formation of an Active Asymmetric Kinase Domain Dimer
Signal Transduction After Activation of RTKs: Phosphotyrosine Residues on the Receptor Are Binding Surfaces for Multiple Proteins with SH2 Domains
Receptor-Mediated Endocytosis and Lysosomal Degradation Squelch Signaling from RTKs
16.2 The Ras/MAP Kinase Signal Transduction Pathway
Ras, a GTPase Switch Protein, Operates Downstream of Most RTKs and Cytokine Receptors
Receptor Tyrosine 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
MAP Kinase Regulates the Activity of Many Transcription Factors Controlling Early Response Genes
Multiple Feedback Mechanisms Restrain MAP Kinase Activation
Scaffold Proteins Isolate Distinct MAP Kinase Pathways in the Same Cell from One Another
16.3 Phosphoinositide Signal Transduction Pathways
Phospholipase Cγ Is Activated by Many RTKs and Cytokine Receptors
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
Activated Protein Kinase B Induces Many Cellular Responses
The PI-3 Kinase Pathway Is Negatively Regulated by PTEN Phosphatase
16.4 Cytokines, Cytokine Receptors, and the JAK/STAT Signaling Pathway
Cytokines Regulate the Development and Function of Many Cell Types
Binding of a Cytokine to Its Receptor Activates One or More Tightly Bound JAK Protein Tyrosine Kinases
JAK Kinases Phosphorylate and Activate STAT Transcription Factors
Multiple Mechanisms Suppress Signaling from Cytokine Receptors
Phosphotyrosine Phosphatases
SOCS Proteins
16.5 The TGF-β Family of Growth Factors, Their Receptor Serine Kinases, and the Smad Transcription Factors They Activate
TGF-β Proteins Are Stored in an Inactive Form in the Extracellular Matrix
Three Separate TGF-β Receptor Proteins Participate in Binding TGF-β and Activating Signal Transduction
Activated RI TGF-β Receptors Phosphorylate Smad Transcription Factors
The R-Smad/co-Smad Complex Activates Expression of Different Genes in Different Cell Types
Negative Feedback Loops Restrain TGF-β/Smad Signaling
16.6 Signal Transduction Pathways That Utilize Regulated, Site-Specific Protein Cleavage: Notch/Delta and EGF Precursors
On Binding Delta, the Notch Receptor Is Cleaved, Releasing a Component Transcription Factor
Metalloproteases Catalyze Cleavage of Many Signaling Proteins from the Cell Surface
16.7 Signal Transduction Pathways That Utilize Proteasomal Degradation of Signaling Components: Wnt, Hedgehog, and the Many Hormones That Activate NF-κB
Wnt Signaling Prevents Destruction of a Transcription Factor by a Cytosolic Protein Complex
Concentration Gradients of Wnt Protein Are Essential for Many Steps in Development
Hedgehog Signaling Relieves Repression of Target Gene Expression
Processing of Hh Precursor Protein
The Hh Receptors Patched and Smoothened and the Downstream Signaling Pathway Were Initially Elucidated by Genetic Studies of Drosophila Development
Feedback Regulation of Hh Signaling
Hedgehog Signaling in Vertebrates Requires Primary Cilia
Degradation of an Inhibitor Protein Activates the NF-κB Transcription Factor
Enormous Signalsomes with Polyubiquitin Chain Scaffolds Link Many Cell Surface Receptors to Downstream Proteins in the NF-κB Pathway
End of Chapter
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Review the Concepts
Chapter 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
The Arp2/3 Complex Nucleates Branched Filament Assembly
Intracellular Movements Can Be Powered by Actin Polymerization
Microfilaments Function in Endocytosis
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
Adapter 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
17.6 Myosin-Powered Movements
Myosin Thick Filaments and Actin Thin Filaments in Skeletal Muscle Slide Past Each Other 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 Carries Vesicles Along Actin Filaments
17.7 Cell Migration: Mechanism, Signaling, and Chemotaxis
Cell Migration Coordinates Force Generation with Cell Adhesion and Membrane Recycling
The 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
End of Chapter
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Review the Concepts
Chapter 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 Configurations
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 Also Promote Microtubule Disassembly
Severing Proteins Also Regulate Microtubule Dynamics
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 (+) Ends of Microtubules
The Kinesins Form a Large Protein Superfamily with Diverse Functions
Kinesin-1 Is a Processive Motor
Dynein Motors Transport Organelles Toward the (−) Ends of Microtubules
Kinesins and Dyneins Cooperate in the Transport of Organelles Throughout the Cell
Tubulin Modifications Distinguish Different Classes of 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 Five Stages
The Mitotic Spindle Contains Three Classes of Microtubules
Microtubule Dynamics Increase Dramatically in Mitosis
Chromosomes Are Captured and Oriented During Prometaphase
Duplicated Chromosomes Are Aligned by Motors and Microtubule Dynamics
The 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
The Spindle Is Centered and Oriented by a Dynein/Dynactin-Dependent Pathway
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 Filaments Are Dynamic
Cytoplasmic Intermediate Filament Proteins Are Expressed in a Tissue-Specific Manner
Lamins Line the Inner Nuclear Envelope to Provide Organization and Rigidity to the Nucleus
Lamins Are Reversibly Disassembled by Phosphorylation During Mitosis
18.8 Coordination and Cooperation Between Cytoskeletal Elements
Intermediate Filament–Associated Proteins Contribute to Cellular Organization
Microfilaments and Microtubules Cooperate to Transport Melanosomes
Cdc42 Coordinates Microtubules and Microfilaments During Cell Migration
Advancement of Neural Growth Cones Is Coordinated by Microfilaments and Microtubules
End of Chapter
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Review the Concepts
Chapter 19 The Eukaryotic Cell Cycle
19.1 Overview of the Cell Cycle
G1 Controls Entry into S Phase
G2 Phase Readies the Cell for Mitosis and Cell Division
Mitosis and Cytokinesis Occur During M-Phase
19.2 Model Organisms and Methods of Studying the Cell Cycle
Budding and Fission Yeasts Are Powerful Systems for Genetic Analysis of the Cell Cycle
Frog Oocytes and Early Embryos Facilitate Biochemical Characterization of the Cell Cycle Machinery
The Study of Tissue Culture Cells Uncovers Cell Cycle Regulation in Mammals
Researchers Use Multiple Tools to Study the Cell Cycle
19.3 Cell Cycle Progression and Control: Feedback Loops and Post-Translational Modification
Cyclin-Dependent Kinases Are Small Protein Kinases That Require a Regulatory Cyclin Subunit for Their Activity
Cyclins Determine the Activity of CDKs
CDKs Are Regulated by Activating and Inhibitory Phosphorylation
CDK Inhibitors Provide Additional Control of Cyclin-CDK Activity
Cyclin Levels Are Regulated by Transcriptional Activation and Ubiquitin-Mediated Protein Degradation
Phosphoserine/Threonine-Binding Domains Build Feedback Loops That Coordinate CDK Activation and Cell Cycle Progression
Mass Spectrometry Studies and Genetically Engineered CDKs Led to the Discovery of New CDK Substrates and Functions
19.4 The Transition from G1 into S Phase and DNA Replication
The G1/S Transition in Budding Yeast Is Controlled by Cyclin-CDK Complexes
The G1–S Phase Transition in Metazoans Involves Cyclin-CDK Control of the E2F Transcription Factor Through Its Regulator Rb
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 The G2/M Transition and the Irreversible Engine of Mitosis
Precipitous Activation of Mitotic CDKs by Positive Feedback Loops Initiates Mitosis
Mitotic CDKs Promote Nuclear Envelope Breakdown
Centrosomes Duplicate During S phase and Separate During Mitosis
Mitotic CDKs, Polo-like Kinases, and Aurora Kinases Drive Assembly of a Mitotic Spindle That Attaches to the Kinetochores of Condensed Chromosomes
Chromosome Condensation Facilitates Chromosome Segregation
19.6 The Mitotic Spindle, Chromosome Segregation, and Exit from Mitosis
Separase-Mediated Cleavage of Cohesins Initiates Chromosome Segregation
APC/C Activates Separase Through Securin Ubiquitinylation
Mitotic CDK Inactivation and Protein De-phosphorylation Triggers Exit from Mitosis
Cytokinesis Creates Two Daughter Cells
19.7 Surveillance Mechanisms in Cell Cycle Regulation
The DNA Damage Response System Halts Cell Cycle Progression and Recruits DNA Repair Machinery When DNA Is Compromised
The Spindle Assembly Checkpoint Pathway Prevents Chromosome Segregation Until Chromosomes Are Accurately Attached to the Mitotic Spindle
19.8 Meiosis: A Special Type of Cell Division
Extracellular and Intracellular Cues Regulate Germ Cell Formation
Several 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
End of Chapter
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Review the Concepts
Chapter 20 Integrating Cells into Tissues
20.1 Cell-Cell and Cell–Extracellular Matrix Adhesion: An Overview
Cell-Adhesion Molecules Bind to One Another and to Intracellular Proteins
The Extracellular Matrix Participates in Adhesion, Signaling, and Other Functions
The Evolution of Multifaceted Adhesion Molecules Enabled the Evolution of Diverse Animal Tissues
Cell-Adhesion Molecules Mediate Mechanotransduction
20.2 Cell-Cell and Cell–Extracellular Matrix Junctions and Their Adhesion Molecules
Epithelial Cells Have Distinct Apical, Lateral, and Basal Surfaces
Three Types of Junctions Mediate Many Cell-Cell and Cell-Matrix Interactions
Cadherins Mediate Cell-Cell Adhesions in Adherens Junctions and Desmosomes
Integrins Mediate Cell-Matrix 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 the Cytosols of Adjacent Cells
Tunneling Nanotubes Can Mediate Metabolic Coupling and Transfer Organelles Between Animal Cells
20.3 The Extracellular Matrix I: The Basal Lamina
The 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
Perlecan, a Proteoglycan, Cross-Links Components of the Basal Lamina and Cell-Surface Receptors
20.4 The 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 Connect Cells and ECM, 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 Mediate Adhesion and Relay Signals Between Cells and Their Three-Dimensional Environment
Regulation of Integrin-Mediated Adhesion and Signaling Controls Cell Function and Movement
Connections Between the ECM and Cytoskeleton Are Defective in Muscular Dystrophy
IgCAMs Mediate Cell-Cell Adhesion in Neural and Other Tissues
Leukocyte Movement into Tissues Is Orchestrated by a Precisely Timed Sequence of Adhesive Interactions
20.6 Plant Tissues
The Plant Cell Wall, a Plant’s ECM, Is a Laminate of Cellulose Fibrils in a Matrix of Polysaccharides and Glycoproteins
Loosening of the Cell Wall Permits Plant Cell Growth
Plasmodesmata Directly Connect the Cytosols of Adjacent Cells
The Molecules That Plants Depend on for Adhesion and Mechanotransduction Differ from Those in Animals
End of Chapter
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Review the Concepts
Chapter 21 Responding to the Cellular Environment
21.1 Regulating Blood Glucose Level
Insulin and Glucagon Work Together to Maintain a Stable Blood Glucose Level
A Rise in Blood Glucose Triggers Insulin Secretion from the β Islet Cells
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
In the Liver, Insulin Inhibits Glucose Synthesis, Accelerates the Rate of Glycolysis, and Enhances Storage of Glucose as Glycogen
21.2 Integrating Cell Growth Signals with Nutrient and Energy Levels
The Active mTORC1 Complex Activates Many Anabolic Signal Transduction Pathways
mTORC1 Kinase Activation Requires Amino Acids, a High ATP:AMP Ratio, and Activation of Signal Transduction Pathways Downstream of Growth-Factor Receptors
21.3 Responding to Changes in the Levels of Cholesterol and Unsaturated Fatty Acids
Fatty Acid and Cholesterol Biosynthesis as Well as Cholesterol Import Are Regulated at the Level of Gene Transcription
The Endoplasmic Reticulum SCAP Protein Senses the Level of Cellular Cholesterol
Regulated Intramembrane Proteolysis of SREBP in the Golgi Releases a bHLH Transcription Factor That Acts to Maintain Appropriate Phospholipid and Cholesterol Levels
21.4 Responding to Low Oxygen
Induction of the Erythropoietin Gene at Low Oxygen Levels
Oxygen Sensing and Regulated Hif-1α Expression Is a Property of All Nucleated Mammalian Cells
Hif-1α Function and Stability Are Blocked at Ambient Oxygen Levels
A Conserved Family of Oxygen-Sensitive Transcription Factors Found in Plants and Animals Is Regulated by Post-Translational Addition of an Arginine Residue
21.5 Responding to Elevated Temperatures
The Heat-Shock Response Is Induced by Unfolded Polypeptide Chains
The Heat-Shock Response Is Regulated Primarily by Related Transcription Factors in All Eukaryotes Called Heat-Shock Factors, Including HSF1 in Humans
21.6 Sensing Night and Day: Circadian Rhythms
The Circadian Clock in Most Organisms Relies on a Negative Feedback Loop
The Circadian Clock in Bacteria: A Different Solution
Suprachiasmatic Nucleus: The Master Clock in Mammals
21.7 Sensing and Responding to the Physical Environment
The Hippo Kinase Cascade Pathway in Drosophila and Mammals
Regulation of the Hippo Kinase Cascade by Cell Interactions with the Extracellular Matrix and by Tension on Actin Filaments
The Hippo Pathway and Early Embryogenesis
End of Chapter
Key Terms
Review the Concepts
Chapter 22 Stem Cells, Cell Asymmetry, and Regulated Cell Death
22.1 Early Mammalian Development, Embryonic Stem Cells, and Induced Pluripotent Stem Cells
Fertilization Unifies the Genome
Cleavage of the Mammalian Embryo Leads to the First Differentiation Events
Pluripotent Cells of the Inner Cell Mass Are the Source of ES Cells
Multiple Factors Control the Pluripotency of ES Cells
Animal Cloning Shows That Epigenetic Changes During Differentiation Can Be Reversed
Somatic Cells Can Generate iPS Cells
Patient-Specific iPS Cells Can Be Used to Develop Potential Treatments for Many Diseases
ES and iPS Cells Can Generate Functional Differentiated Human Cells
22.2 Stem Cells and Niches in Multicellular Organisms
Adult Planarians Contain Pluripotent Stem Cells
Multipotent Somatic Stem Cells Give Rise to Both Stem Cells and Differentiating Cells
Stem Cells for Different Tissues Occupy Sustaining Niches
Germ-Line Stem Cells in Many Organisms Produce Sperm or Oocytes
Intestinal Stem Cells Continuously Generate All the Cells of the Intestinal Epithelium
Wnt and R-Spondins Are Essential for Function of the Lgr5+ Intestinal Stem Cells
Hematopoietic Stem Cells Form All Blood Cells and All Cells of the Immune System
Characterizing Hematopoietic Stem Cells by Transplantation
Niches for Hematopoietic Stem Cells and Many Hematopoietic Progenitor Cells
Regulating the Production of Differentiated Hematopoietic Cells
Meristems Are Niches for Stem Cells in Plants
A Negative Feedback Loop Maintains the Size of the Shoot Apical Stem-Cell Population
The Root Meristem Resembles the Shoot Meristem in Structure and Function
22.3 Mechanisms of Cell Polarity and Asymmetric Cell Division
The Intrinsic Polarity Program Depends on a Positive Feedback Loop Involving Cdc42
Cell Polarization Before Cell Division Follows a Common Hierarchy of Steps
Polarized Membrane Traffic Allows Yeast to Grow Asymmetrically During Mating
The Par Proteins Direct Cell Asymmetry in the Nematode Embryo
The Par Proteins and Other Polarity Complexes Are Involved in Epithelial-Cell Polarity
The Planar Cell Polarity Pathway Orients Cells Within an Epithelium
The Par Proteins Are Involved in Asymmetric Division of Stem Cells
22.4 Cell Death and Its Regulation
Most 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
Phosphatidylserine: an “Eat Me” Signal on the Surface of Apoptotic Cells
Neurotrophins Promote Survival of Neurons
Mitochondria Play a Central Role in Regulation of Apoptosis in Vertebrate Cells
The Pro-Apoptotic Proteins Bax and Bak Form Pores and Holes in the Outer Mitochondrial Membrane
Release of SMAC/DIABLO Proteins from Mitochondria Also Promotes Caspase Activation
Trophic Factors Induce Inactivation of Bad, a Pro-apoptotic BH3-Only Protein
Apoptosis in Vertebrates Is Induced by BH3-Only Pro-apoptotic Proteins That Are Activated by Environmental Stresses
Apoptosis and Necroptosis Can Be Triggered by Tumor Necrosis Factor, Fas Ligand, and Related Death Proteins
End of Chapter
Key Terms
Review the Concepts
Chapter 23 Cells of the Nervous System
23.1 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
The Nervous System Uses Signaling Circuits Composed of Multiple Types of Neurons
Glial Cells Form Myelin Sheaths and Support Neurons
Neural Stem Cells Form Nerve and Glial Cells in the Central Nervous System
23.2 Voltage-Gated Ion Channels and the Propagation of Action Potentials
The 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
All Voltage-Gated Ion Channels Have Similar Structures
Voltage-Sensing S4 α Helices Move in Response to Membrane Depolarization
Movement of the Channel-Inactivating Segment into the Open Pore Blocks Ion Flow
Myelination Increases the Velocity of Impulse Conduction
Action Potentials “Jump” from Node to Node in Myelinated Axons
Two Types of Glia Produce Myelin Sheaths
Light-Activated Ion Channels and Optogenetics
23.3 Communication at Synapses
Formation of Synapses Requires Assembly of Presynaptic and Postsynaptic Structures
Neurotransmitters Are Transported into Synaptic Vesicles by H+-Linked Antiport Proteins
Three Pools of Synaptic Vesicles Loaded with Neurotransmitter Are Present in the Presynaptic Terminal
Influx of Ca2+ Triggers Release of Neurotransmitters
A 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 Integrate Many Inputs to Make an All-or-None Decision to Generate an Action Potential
Gap Junctions Allow Direct Communication Between Neurons and Between Glia
23.4 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
The Largest Group of G Protein–Coupled Receptors Detect Odors
Each Olfactory Receptor Neuron Expresses a Single Type of Odorant Receptor
23.5 Forming and Storing Memories
Memories Are Formed by Changing the Number or Strength of Synapses Between Neurons
The Hippocampus Is Required for Memory Formation
Multiple Molecular Mechanisms Contribute to Synaptic Plasticity
Formation of Long-Term Memories Requires Gene Expression
End of Chapter
Key Terms
Review the Concepts
Chapter 24 Immunology
24.1 Overview of Host Defenses
Pathogens Enter the Body Through Different Routes and Replicate at Different Sites
Cells of the Innate and Adaptive Immune Systems 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
Inflammation Is a Complex Response to Injury That Encompasses Both Innate and Adaptive Immunity and Helps Destroy Pathogens
Adaptive Immunity, the Third Line of Defense, Exhibits Specificity
24.2 Immunoglobulins: Structure and Function
Immunoglobulins Have a Conserved Structure Consisting of Heavy and Light Chains
Multiple Immunoglobulin Isotypes Exist, Each with Different Functions
Each Naive B Cell Produces a Unique Immunoglobulin
Immunoglobulin Domains Have a Characteristic Fold Composed of Two β Sheets Stabilized by a Disulfide Bond
An Immunoglobulin’s Constant Region Determines Its Functional Properties
24.3 Generation of Antibody Diversity and B-Cell Development
A 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
24.4 The MHC and Antigen Presentation
The MHC Determines the Ability of Two Unrelated Individuals of the Same Species to Accept or Reject Grafts
The 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 Are Highly Polymorphic, Bind Peptide Antigens, and Interact with the T-Cell Receptor
In Antigen Presentation, Protein Fragments Are Complexed with MHC Products and Posted to the Cell Surface
The Class I MHC Pathway Presents Cytosolic Antigens
The Class II MHC Pathway Presents Antigens Delivered to the Endocytic Pathway
24.5 T Cells, T-Cell Receptors, and T-Cell Development
The 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
Many of the Variable Residues of TCRs Are 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 Commit to the CD4 or CD8 Lineage in the Thymus
T Cells Require Two Types of Signals for Full Activation
Cytotoxic T Cells Carry the CD8 Co-Receptor and Are Specialized for Killing
T Cells Secrete an Array of Cytokines That Provide Signals to Other Immune-System Cells
Helper T Cells Are Divided into Distinct Subsets Based on Their Cytokine Production and Expression of Surface Markers
Innate Lymphoid Cells Regulate Inflammation and the Overall Immune Response
Leukocytes Move in Response to Chemotactic Cues Provided by Chemokines
24.6 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
The Immune System Defends Against Cancer
End of Chapter
Key Terms
Review the Concepts
Chapter 25 Cancer
25.1 How Tumor Cells Differ from Normal Cells
The Genetic Makeup of Most Cancer Cells Is Dramatically Altered
Uncontrolled Proliferation Is a Universal Trait of Cancer
Cellular Housekeeping Functions Are Fundamentally Altered in Cancer Cells
Cancer Cells Exhibit Altered Cell-Cell Interactions to Form Heterogeneous Organs
Tumor Growth Requires Formation of New Blood Vessels
Invasion and Metastasis Are Late Stages of Tumorigenesis
25.2 Genetic and Genomic Basis of Cancer
Carcinogens Induce Cancer by Damaging DNA
Some Carcinogens Have Been Linked to Specific Cancers
Familial Syndromes That Cause Loss of DNA Repair Can Lead to Cancer
Somatic Mutations in the DNA Damage Response Pathway Are Oncogenic
Cancer Genome Sequencing Reveals an Enormous Diversity of Somatic Mutations
Oncogenes Were Discovered by Their Association with Tumor Viruses
Single Oncogenic Drivers Can Be Activated by Chromosome Rearrangements
Inherited Predisposition for Cancer Enabled Identification of Some Oncogenic Drivers
Oncogenic Driver Mutations Have Been Identified in Many Genes
Oncogenic Driver Mutations Can Be Identified by Comparing Cancer Genomes
Oncogenic Drivers Can Be Gain-of-Function or Loss-of-Function Mutations
Tumor Suppressor Genes and Oncogenes Often Operate in the Same Pathway
MicroRNAs Can Promote and Inhibit Tumorigenesis
Epigenetic Changes Can Contribute to Tumorigenesis
25.3 Dysregulation of Cell Growth and Developmental Pathways Initiates Tumorigenesis
Receptor Mutations Can Cause Proliferation in the Absence of External Growth Factors
Many Oncogenic Mutations Constitutively Activate Signal-Transducing Proteins
Growth Control Pathways Ultimately Regulate Initiation of the Cell Cycle
Inappropriate Production of Nuclear Transcription Factors Can Induce Transformation
Aberrations in Signaling Pathways That Control Development Are Associated with Many Cancers
Experimental Reconstruction of the Multi-Hit Model for Cancer
The Succession of Oncogenic Mutations Can Be Traced in Colon Cancers
Cancer Development Can Be Studied in Animal Models
Molecular Cell Biology Is Changing How Cancer Is Diagnosed and Treated
25.4 Evasion of Programmed Cell Death and Immune Surveillance Processes
Oncogenic Driver Mutations Enable Cancer Cells to Evade Apoptosis
p53 Can Activate Either the DNA Damage Checkpoint or Apoptosis in Response to DNA Damage
The Immune System Is a Second Line of Defense Against Cancer Formation
The Tumor Microenvironment and Immunoediting Limit the Ability of the Immune System to Detect and Kill Established Tumors
Activation of the Immune System Presents a Major Opening for Cancer Therapy
End of Chapter
Key Terms
Review the Concepts
Index
Glossary (online and e-book only)
References (online and e-book only)
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