1:The Evolution of the Cell
[View]Simple Biological Molecules Can Form Under Prebiotic Conditions
[View]Complex Chemical Systems Can Develop in an Environment That Is Far from Chemical Equilibrium
[View]Polynucleotides Are Capable of Directing Their Own Synthesis
[View]Self-replicating Molecules Undergo Natural Selection
[View]Specialized RNA Molecules Can Catalyze Biochemical Reactions
[View]Information Flows from Polynucleotides to Polypeptides
[View]Membranes Defined the First Cell
[View]All Present-Day Cells Use DNA as Their Hereditary Material
[View]Summary
[View]Introduction
[View]Procaryotic Cells Are Structurally Simple but Biochemically Diverse
[View]Metabolic Reactions Evolve
[View]Evolutionary Relationships Can Be Deduced by Comparing DNA Sequences
[View]Cyanobacteria Can Fix CO₂ and N₂
[View]Bacteria Can Carry Out the Aerobic Oxidation of Food Molecules
[View]Eucaryotic Cells Contain Several Distinctive Organelles
[View]Eucaryotic Cells Depend on Mitochondria for Their Oxidative Metabolism
[View]Chloroplasts Are the Descendants of an Engulfed Procaryotic Cell
[View]Eucaryotic Cells Contain a Rich Array of Internal Membranes
[View]Eucaryotic Cells Have a Cytoskeleton
[View]Protozoa Include the Most Complex Cells Known
[View]In Eucaryotic Cells the Genetic Material Is Packaged in Complex Ways
[View]Summary
[View]Introduction
[View]Single Cells Can Associate to Form Colonies
[View]The Cells of a Higher Organism Become Specialized and Cooperate
[View]Multicellular Organization Depends on Cohesion Between Cells
[View]Epithelial Sheets of Cells Enclose a Sheltered Internal Environment
[View]Cell-Cell Communication Controls the Spatial Pattern of Multicellular Organisms
[View]Cell Memory Permits the Development of Complex Patterns
[View]Basic Developmental Programs Tend to Be Conserved in Evolution
[View]The Cells of the Vertebrate Body Exhibit More Than 200 Different Modes of Specialization
[View]Genes Can Be Switched On and Off
[View]Sequence Comparisons Reveal Hundreds of Families of Homologous Genes
[View]Summary
2:Small Molecules, Energy, and Biosynthesis
[View]Cell Chemistry Is Based on Carbon Compounds
[View]Cells Use Four Basic Types of Small Molecules
[View]Sugars Are Food Molecules of the Cell
[View]Fatty Acids Are Components of Cell Membranes
[View]Amino Acids Are the Subunits of Proteins
[View]Nucleotides Are the Subunits of DNA and RNA
[View]Summary
[View]Introduction
[View]Biological Order Is Made Possible by the Release of Heat Energy from Cells
[View]Photosynthetic Organisms Use Sunlight to Synthesize Organic Compounds
[View]Chemical Energy Passes from Plants to Animals
[View]Cells Obtain Energy by the Oxidation of Biological Molecules
[View]The Breakdown of an Organic Molecule Takes Place in a Sequence of Enzyme-catalyzed Reactions
[View]Part of the Energy Released in Oxidation Reactions Is Coupled to the Formation of ATP
[View]The Hydrolysis of ATP Generates Order in Cells
[View]Summary
[View]Introduction
[View]Glycolysis Can Produce ATP Even in the Absence of Oxygen
[View]NADH Is a Central Intermediate in Oxidative Catabolism
[View]Metabolism Is Dominated by the Citric Acid Cycle
[View]In Oxidative Phosphorylation the Transfer of Electrons to Oxygen Drives ATP Formation
[View]Amino Acids and Nucleotides Are Part of the Nitrogen Cycle
[View]Summary
[View]Introduction
[View]The Free-Energy Change for a Reaction Determines Whether It Can Occur
[View]Biosynthetic Reactions Are Often Directly Coupled to ATP Hydrolysis
[View]Coenzymes Are Involved in the Transfer of Specific Chemical Groups
[View]The Structure of Coenzymes Suggests That They May Have Originated in an RNA World
[View]Biosynthesis Requires Reducing Power
[View]Biological Polymers Are Synthesized by Repetition of Elementary Dehydration Reactions
[View]Summary
[View]Metabolism Is Organized and Regulated
[View]Metabolic Pathways Are Regulated by Changes in Enzyme Activity
[View]Catabolic Reactions Can Be Reversed by an Input of Energy
[View]Enzymes Can Be Switched On and Off by Covalent Modification
[View]Reactions Are Compartmentalized Both Within Cells and Within Organisms
[View]Summary
3:Macromolecules: Structure, Shape, and Information
[View]Introduction
[View]The Specific Interactions of a Macromolecule Depend on Weak, Noncovalent Bonds
[View]A Helix Is a Common Structural Motif in Biological Structures Made from Repeated Subunits
[View]Diffusion Is the First Step to Molecular Recognition
[View]Thermal Motions Bring Molecules Together and Then Pull Them Apart
[View]The Equilibrium Constant Is a Measure of the Strength of an Interaction Between Two Molecules
[View]Atoms and Molecules Move Very Rapidly
[View]Molecular Recognition Processes Can Never Be Perfect
[View]Summary
[View]Genes Are Made of DNA
[View]DNA Molecules Consist of Two Long Chains Held Together by Complementary Base Pairs
[View]The Structure of DNA Provides an Explanation for Heredity
[View]Errors in DNA Replication Cause Mutations
[View]The Nucleotide Sequence of a Gene Determines the Amino Acid Sequence of a Protein
[View]Portions of DNA Sequence Are Copied into RNA Molecules That Guide Protein Synthesis
[View]Eucaryotic RNA Molecules Are Spliced to Remove Intron Sequences
[View]Sequences of Nucleotides in mRNA Are "Read" in Sets of Three and Translated into Amino Acids
[View]tRNA Molecules Match Amino Acids to Groups of Nucleotides
[View]The RNA Message Is Read from One End to the Other by a Ribosome
[View]Some RNA Molecules Function as Catalysts
[View]Summary
[View]Introduction
[View]The Shape of a Protein Molecule Is Determined by Its Amino Acid Sequence
[View]Common Folding Patterns Recur in Different Protein Chains
[View]Proteins Are Amazingly Versatile Molecules
[View]Proteins Have Different Levels of Structural Organization
[View]Domains Are Formed from a Polypeptide Chain That Winds Back and Forth, Making Sharp Turns at the Protein Surface
[View]Relatively Few of the Many Possible Polypeptide Chains Would Be Useful
[View]New Proteins Usually Evolve by Alterations of Old Ones
[View]New Proteins Can Evolve by Recombining Preexisting Polypeptide Domains
[View]Structural Homologies Can Help Assign Functions to Newly Discovered Proteins
[View]Protein Subunits Can Assemble into Large Structures
[View]A Single Type of Protein Subunit Can Interact with Itself to Form Geometrically Regular Assemblies
[View]Coiled-Coil Proteins Help Build Many Elongated Structures in Cells
[View]Proteins Can Assemble into Sheets, Tubes, or Spheres
[View]Many Structures in Cells Are Capable of Self-assembly
[View]Not All Biological Structures Form by Self-assembly
[View]Summary
[View]Introduction
[View]A Protein's Conformation Determines Its Chemistry
[View]Substrate Binding Is the First Step in Enzyme Catalysis
[View]Enzymes Speed Reactions by Selectively Stabilizing Transition States
[View]Enzymes Can Promote the Making and Breaking of Covalent Bonds Through Simultaneous Acid and Base Catalysis
[View]Enzymes Can Further Increase Reaction Rates by Forming Covalent Intermediates with Their Substrates
[View]Enzymes Accelerate Chemical Reactions but Cannot Make Them Energetically More Favorable
[View]Enzymes Determine Reaction Paths by Coupling Selected Reactions to ATP Hydrolysis
[View]Multienzyme Complexes Help to Increase the Rate of Cell Metabolism
[View]Summary
4:How Cells Are Studied
[View]Introduction
[View]The Light Microscope Can Resolve Details 0.2 microns Apart
[View]Tissues Are Usually Fixed and Sectioned for Microscopy
[View]Different Components of the Cell Can Be Selectively Stained
[View]Specific Molecules Can Be Located in Cells by Fluorescence Microscopy
[View]Living Cells Are Seen Clearly in a Phase-Contrast or a Differential-Interference-Contrast Microscope
[View]Images Can Be Enhanced and Analyzed by Electronic Techniques
[View]Imaging of Complex Three-dimensional Objects Is Possible with the Confocal Scanning Microscope
[View]The Electron Microscope Resolves the Fine Structure of the Cell
[View]Biological Specimens Require Special Preparation for the Electron Microscope
[View]Three-dimensional Images of Surfaces Can Be Obtained by Scanning Electron Microscopy
[View]Metal Shadowing Allows Surface Features to Be Examined at High Resolution by Transmission Electron Microscopy
[View]Freeze-Fracture and Freeze-Etch Electron Microscopy Provide Unique Views of the Cell Interior
[View]Negative Staining and Cryoelectron Microscopy Allow Macromolecules to Be Viewed at High Resolution
[View]Summary
[View]Introduction
[View]Cells Can Be Isolated from a Tissue and Separated into Different Types
[View]Cells Can Be Grown in a Culture Dish
[View]Serum-free, Chemically Defined Media Permit Identification of Specific Growth Factors
[View]Eucaryotic Cell Lines Are a Widely Used Source of Homogeneous Cells
[View]Cells Can Be Fused Together to Form Hybrid Cells
[View]Summary
[View]Introduction
[View]Organelles and Macromolecules Can Be Separated by Ultracentrifugation
[View]The Molecular Details of Complex Cellular Processes Can Be Deciphered in Cell-free Systems
[View]Proteins Can Be Separated by Chromatography
[View]The Size and Subunit Composition of a Protein Can Be Determined by SDS Polyacrylamide-Gel Electrophoresis
[View]More Than 1000 Proteins Can Be Resolved on a Single Gel by Two-dimensional Polyacrylamide-Gel Electrophoresis
[View]Selective Cleavage of a Protein Generates a Distinctive Set of Peptide Fragments
[View]Short Amino Acid Sequences Can Be Analyzed by Automated Machines
[View]The Diffraction of X-rays by Protein Crystals Can Reveal a Protein's Exact Structure
[View]Molecular Structure Can Also Be Determined Using Nuclear Magnetic Resonance (NMR) Spectroscopy
[View]Summary
[View]Introduction
[View]Radioactive Atoms Can Be Detected with Great Sensitivity
[View]Radioisotopes Are Used to Trace Molecules in Cells and Organisms
[View]Ion Concentrations Can Be Measured with Intracellular Electrodes
[View]Rapidly Changing Intracellular Ion Concentrations Can Be Measured with Light-emitting Indicators
[View]There Are Several Ways of Introducing Membrane-impermeant Molecules into Cells
[View]The Light-induced Activation of "Caged" Precursor Molecules Facilitates Studies of Intracellular Dynamics
[View]Antibodies Can Be Used to Detect and Isolate Specific Molecules
[View]Hybridoma Cell Lines Provide a Permanent Source of Monoclonal Antibodies
[View]Summary
5:Protein Function
[View]Introduction
[View]The Binding of a Ligand Can Change the Shape of a Protein
[View]Two Ligands That Bind to the Same Protein Often Affect Each Other's Binding
[View]Two Ligands Whose Binding Sites Are Coupled Must Reciprocally Affect Each Other's Binding
[View]Allosteric Transitions Help Regulate Metabolism
[View]Proteins Often Form Symmetrical Assemblies That Undergo Cooperative Allosteric Transitions
[View]The Allosteric Transition in Aspartate Transcarbamoylase Is Understood in Atomic Detail
[View]Protein Phosphorylation Is a Common Way of Driving Allosteric Transitions in Eucaryotic Cells
[View]A Eucaryotic Cell Contains Many Protein Kinases and Phosphatases
[View]The Structure of Cdk Protein Kinase Shows How a Protein Can Function as a Microchip
[View]Proteins That Bind and Hydrolyze GTP Are Ubiquitous Cellular Regulators
[View]Other Proteins Control the Activity of GTP-binding Proteins by Determining Whether GTP or GDP Is Bound
[View]The Allosteric Transition in EF-Tu Protein Shows How Large Movements Can Be Generated from Small Ones
[View]Proteins That Hydrolyze ATP Do Mechanical Work in Cells
[View]The Structure of Myosin Reveals How Muscles Exert Force
[View]ATP-driven Membrane-bound Allosteric Proteins Can Either Act as Ion Pumps or Work in Reverse to Synthesize ATP
[View]Energy-coupled Allosteric Transitions in Proteins Allow the Proteins to Function as Motors, Clocks, Assembly Factors, or Transducers of Information
[View]Proteins Often Form Large Complexes That Function as Protein Machines
[View]Summary
[View]Introduction
[View]Proteins Are Thought to Fold Through a Molten Globule Intermediate
[View]Molecular Chaperones Facilitate Protein Folding
[View]Many Proteins Contain a Series of Independently Folded Modules
[View]Modules Confer Versatility and Often Mediate Protein-Protein Interactions
[View]Proteins Can Bind to Each Other Through Several Types of Interfaces
[View]Linkage and Selective Proteolysis Ensure All-or-None Assembly
[View]Ubiquitin-dependent Proteolytic Pathways Are Largely Responsible for Selective Protein Turnover in Eucaryotes
[View]The Lifetime of a Protein Can Be Determined by Enzymes That Alter Its N-Terminus
[View]Summary
6:Basic Genetic Mechanisms
[View]Introduction
[View]RNA Polymerase Copies DNA into RNA: The Process of DNA Transcription
[View]Only Selected Portions of a Chromosome Are Used to Produce RNA Molecules
[View]Transfer RNA Molecules Act as Adaptors That Translate Nucleotide Sequences into Protein Sequences
[View]Specific Enzymes Couple Each Amino Acid to Its Appropriate tRNA Molecule
[View]Amino Acids Are Added to the Carboxyl-Terminal End of a Growing Polypeptide Chain
[View]The Genetic Code Is Degenerate
[View]The Events in Protein Synthesis Are Catalyzed on the Ribosome
[View]A Ribosome Moves Stepwise Along the mRNA Chain
[View]A Protein Chain Is Released from the Ribosome When Any One of Three Stop Codons Is Reached
[View]The Initiation Process Sets the Reading Frame for Protein Synthesis
[View]Only One Species of Polypeptide Chain Is Usually Synthesized from Each mRNA Molecule in Eucaryotes
[View]The Binding of Many Ribosomes to an Individual mRNA Molecule Generates Polyribosomes
[View]The Overall Rate of Protein Synthesis in Eucaryotes Is Controlled by Initiation Factors
[View]The Fidelity of Protein Synthesis Is Improved by Two Proofreading Mechanisms
[View]Many Inhibitors of Procaryotic Protein Synthesis Are Useful as Antibiotics
[View]How Did Protein Synthesis Evolve?
[View]Summary
[View]Introduction
[View]DNA Sequences Are Maintained with Very High Fidelity
[View]The Observed Mutation Rates in Proliferating Cells Are Consistent with Evolutionary Estimates
[View]Most Mutations in Proteins Are Deleterious and Are Eliminated by Natural Selection
[View]Low Mutation Rates Are Necessary for Life as We Know It
[View]Low Mutation Rates Mean That Related Organisms Must Be Made from Essentially the Same Proteins
[View]If Left Uncorrected, Spontaneous DNA Damage Would Rapidly Change DNA Sequences
[View]The Stability of Genes Depends on DNA Repair
[View]DNA Damage Can Be Removed by More Than One Pathway
[View]Cells Can Produce DNA Repair Enzymes in Response to DNA Damage
[View]The Structure and Chemistry of the DNA Double Helix Make It Easy to Repair
[View]Summary
[View]Introduction
[View]Base-pairing Underlies DNA Replication as well as DNA Repair
[View]The DNA Replication Fork Is Asymmetrical
[View]The High Fidelity of DNA Replication Requires a Proofreading Mechanism
[View]Only DNA Replication in the 5'-to-3' Direction Allows Efficient Error Correction
[View]A Special Nucleotide Polymerizing Enzyme Synthesizes Short RNA Primer Molecules on the Lagging Strand
[View]Special Proteins Help Open Up the DNA Double Helix in Front of the Replication Fork
[View]A Moving DNA Polymerase Molecule Is Kept Tethered to the DNA by a Sliding Ring
[View]The Proteins at a Replication Fork Cooperate to Form a Replication Machine
[View]A Mismatch Proofreading System Removes Replication Errors That Escape from the Replication Machine
[View]Replication Forks Initiate at Replication Origins
[View]DNA Topoisomerases Prevent DNA Tangling During Replication
[View]DNA Replication Is Basically Similar in Eucaryotes and Procaryotes
[View]Summary
[View]Introduction
[View]General Recombination Is Guided by Base-pairing Interactions Between Complementary Strands of Two Homologous DNA Molecules
[View]General Recombination Can Be Initiated at a Nick in One Strand of a DNA Double Helix
[View]DNA Hybridization Reactions Provide a Simple Model for the Base-pairing Step in General Recombination
[View]The RecA Protein Enables a DNA Single Strand to Pair with a Homologous Region of DNA Double Helix in E. coli
[View]General Genetic Recombination Usually Involves a Cross-Strand Exchange
[View]Gene Conversion Results from Combining General Recombination and Limited DNA Synthesis
[View]Mismatch Proofreading Can Prevent Promiscuous Genetic Recombination Between Two Poorly Matched DNA Sequences
[View]Site-specific Recombination Enzymes Move Special DNA Sequences into and out of Genomes
[View]Transpositional Recombination Can Insert a Mobile Genetic Element into Any DNA Sequence
[View]Summary
[View]Introduction
[View]Viruses Are Mobile Genetic Elements
[View]The Outer Coat of a Virus May Be a Protein Capsid or a Membrane Envelope
[View]Viral Genomes Come in a Variety of Forms and Can Be Either RNA or DNA
[View]A Viral Chromosome Codes for Enzymes Involved in the Replication of Its Nucleic Acid
[View]Both RNA Viruses and DNA Viruses Replicate Through the Formation of Complementary Strands
[View]Viruses Exploit the Intracellular Traffic Machinery of their Host Cells
[View]Different Enveloped Viruses Bud from Different Cellular Membranes
[View]Viral Chromosomes Can Integrate into Host Chromosomes
[View]The Continuous Synthesis of Some Viral Proteins Can Make Cells Cancerous
[View]RNA Tumor Viruses Are Retroviruses
[View]The Virus That Causes AIDS Is a Retrovirus
[View]Some Transposable Elements Are Close Relatives of Retroviruses
[View]Other Transposable Elements Transfer Themselves Directly from One Site in the Genome to Another
[View]Most Viruses Probably Evolved from Plasmids
[View]Summary
7:Recombinant DNA Technology
[View]Introduction
[View]Restriction Nucleases Hydrolyze DNA Molecules at Specific Nucleotide Sequences
[View]Restriction Maps Show the Distribution of Short Marker Nucleotide Sequences Along a Chromosome
[View]Gel Electrophoresis Separates DNA Molecules of Different Sizes
[View]Purified DNA Molecules Can Be Specifically Labeled with Radioisotopes or Chemical Markers in Vitro
[View]Isolated DNA Fragments Can Be Rapidly Sequenced
[View]DNA Footprinting Reveals the Sites Where Proteins Bind on a DNA Molecule
[View]Summary
[View]Introduction
[View]Nucleic Acid Hybridization Reactions Provide a Sensitive Way of Detecting Specific Nucleotide Sequences
[View]Northern and Southern Blotting Facilitate Hybridization with Electrophoretically Separated Nucleic Acid Molecules
[View]RFLP Markers Greatly Facilitate Genetic Approaches to the Mapping and Analysis of Large Genomes
[View]Synthetic DNA Molecules Facilitate the Prenatal Diagnosis of Genetic Diseases
[View]Hybridization at Reduced Stringency Allows Even Distantly Related Genes to Be Identified
[View]In Situ Hybridization Techniques Locate Specific Nucleic Acid Sequences in Cells or on Chromosomes
[View]Summary
[View]Introduction
[View]A DNA Library Can Be Made Using Either Viral or Plasmid Vectors
[View]Two Types of DNA Libraries Serve Different Purposes
[View]cDNA Clones Contain Uninterrupted Coding Sequences
[View]cDNA Libraries Can Be Prepared from Selected Populations of mRNA Molecules
[View]Either a DNA Probe or a Test for Expressed Protein Can Be Used to Identify the Clones of Interest in a DNA Library
[View]In Vitro Translation Facilitates Identification of the Correct DNA Clone
[View]The Selection of Overlapping DNA Clones Allows One to "Walk" Along the Chromosome to a Nearby Gene of Interest
[View]Ordered Genomic Clone Libraries Are Being Produced for Selected Organisms
[View]Positional DNA Cloning Reveals Human Genes with Unanticipated Functions
[View]Selected DNA Segments Can Be Cloned in a Test Tube by a Polymerase Chain Reaction
[View]Summary
[View]Introduction
[View]New DNA Molecules of Any Sequence Can Be Formed by Joining Together DNA Fragments
[View]Homogeneous RNA Molecules Can Be Produced in Large Quantities by DNA Transcription in Vitro
[View]Rare Cellular Proteins Can Be Made in Large Amounts Using Expression Vectors
[View]Reporter Genes Enable Regulatory DNA Sequences to Be Dissected
[View]Mutant Organisms Best Reveal the Function of a Gene
[View]Cells Containing Mutated Genes Can Be Made to Order
[View]Genes Can Be Redesigned to Produce Proteins of Any Desired Sequence
[View]Fusion Proteins Are Often Useful for Analyzing Protein Function
[View]Normal Genes Can Be Easily Replaced by Mutant Ones in Bacteria and Some Lower Eucaryotes
[View]Engineered Genes Can Be Used to Create Specific Dominant Mutations in Diploid Organisms
[View]Engineered Genes Can Be Permanently Inserted into the Germ Line of Mice or Fruit Flies to Produce Transgenic Animals
[View]Gene Targeting Makes It Possible to Produce Transgenic Mice That Are Missing Specific Genes
[View]Transgenic Plants Are Important for Both Cell Biology and Agriculture
[View]Summary
8:The Cell Nucleus
[View]Introduction
[View]Each DNA Molecule That Forms a Linear Chromosome Must Contain a Centromere, Two Telomeres, and Replication Origins
[View]Most Chromosomal DNA Does Not Code for Proteins or RNAs
[View]Each Gene Produces an RNA Molecule
[View]Comparisons Between the DNAs of Related Organisms Distinguish Conserved and Nonconserved Regions of DNA Sequence
[View]Histones Are the Principal Structural Proteins of Eucaryotic Chromosomes
[View]Histones Associate with DNA to Form Nucleosomes, the Unit Particles of Chromatin
[View]The Positioning of Nucleosomes on DNA Is Determined by the Propensity of the DNA to Form Tight Loops and by the Presence of Other DNA-bound Proteins
[View]Nucleosomes Are Usually Packed Together by Histone H1 to Form Regular Higher-Order Structures
[View]Summary
[View]Introduction
[View]Lampbrush Chromosomes Contain Loops of Decondensed Chromatin
[View]Orderly Domains of Interphase Chromatin Also Can Be Seen in Insect Polytene Chromosomes
[View]Individual Chromatin Domains Can Unfold and Refold as a Unit
[View]Both Bands and Interbands in Polytene Chromosomes Are Likely to Contain Genes
[View]Transcriptionally Active Chromatin Is Less Condensed
[View]Active Chromatin Is Biochemically Distinct
[View]Heterochromatin Is Highly Condensed and Transcriptionally Inactive
[View]Mitotic Chromosomes Are Formed from Chromatin in Its Most Condensed State
[View]Each Mitotic Chromosome Contains a Characteristic Pattern of Very Large Domains
[View]Summary
[View]Introduction
[View]Specific DNA Sequences Serve as Replication Origins
[View]A Mammalian Cell-free System Replicates the Chromosome of a Monkey Virus
[View]Replication Origins Are Activated in Clusters on Higher Eucaryotic Chromosomes
[View]Different Regions on the Same Chromosome Replicate at Distinct Times
[View]Highly Condensed Chromatin Replicates Late, While Genes in Active Chromatin Replicate Early
[View]The Late-replicating Replication Units Coincide with the A-T-rich Bands on Metaphase Chromosomes
[View]The Controlled Timing of DNA Replication May Contribute to Cell Memory
[View]Chromatin-bound Factors Ensure That Each Region of the DNA Is Replicated Only Once
[View]New Histones Are Assembled into Chromatin as DNA Replicates
[View]Telomeres Consist of Short G-rich Repeats That Are Added to Chromosome Ends by Telomerase
[View]Summary
[View]Introduction
[View]RNA Polymerase Exchanges Subunits as It Begins Each RNA Chain
[View]Three Kinds of RNA Polymerase Make RNA in Eucaryotes
[View]RNA Polymerase II Transcribes Some DNA Sequences Much More Often Than Others
[View]The Precursors of Messenger RNA Are Covalently Modified at Both Ends
[View]RNA Processing Removes Long Nucleotide Sequences from the Middle of RNA Molecules
[View]hnRNA Transcripts Are Immediately Coated with Proteins and snRNPs
[View]Intron Sequences Are Removed as Lariat-shaped RNA Molecules
[View]Multiple Intron Sequences Are Usually Removed from Each RNA Transcript
[View]Studies of Thalassemia Reveal How RNA Splicing Can Allow New Proteins to Evolve
[View]Spliceosome-catalyzed RNA Splicing Probably Evolved from Self-splicing Mechanisms
[View]The Transport of mRNAs to the Cytoplasm Is Delayed Until Splicing Is Complete
[View]Ribosomal RNAs (rRNAs) Are Transcribed from Tandemly Arranged Sets of Identical Genes
[View]The Nucleolus Is a Ribosome-producing Machine
[View]The Nucleolus Is a Highly Organized Subcompartment of the Nucleus
[View]The Nucleolus Is Reassembled on Specific Chromosomes After Each Mitosis
[View]Individual Chromosomes Occupy Discrete Territories in the Nucleus During Interphase
[View]How Well Ordered Is the Nucleus?
[View]Summary
[View]Introduction
[View]Genomes Are Fine-tuned by Point Mutation and Radically Remodeled or Enlarged by Genetic Recombination
[View]Tandemly Repeated DNA Sequences Tend to Remain the Same
[View]The Evolution of the Globin Gene Family Shows How Random DNA Duplications Contribute to the Evolution of Organisms
[View]Genes Encoding New Proteins Can Be Created by the Recombination of Exons
[View]Most Proteins Probably Originated from Highly Split Genes
[View]A Major Fraction of the DNA of Higher Eucaryotes Consists of Repeated, Noncoding Nucleotide Sequences
[View]Satellite DNA Sequences Have No Known Function
[View]The Evolution of Genomes Has Been Accelerated by Transposable Elements
[View]Transposable Elements Often Affect Gene Regulation
[View]Transposition Bursts Cause Cataclysmic Changes in Genomes and Increase Biological Diversity
[View]About 10% of the Human Genome Consists of Two Families of Transposable Elements
[View]Summary
9:Control of Gene Expression
[View]Introduction
[View]The Different Cell Types of a Multicellular Organism Contain the Same DNA
[View]Different Cell Types Synthesize Different Sets of Proteins
[View]A Cell Can Change the Expression of Its Genes in Response to External Signals
[View]Gene Expression Can Be Regulated at Many of the Steps in the Pathway from DNA to RNA to Protein
[View]Summary
[View]Introduction
[View]Gene Regulatory Proteins Were Discovered Using Bacterial Genetics
[View]The Outside of the DNA Helix Can Be Read by Proteins
[View]The Geometry of the DNA Double Helix Depends on the Nucleotide Sequence
[View]Short DNA Sequences Are Fundamental Components of Genetic Switches
[View]Gene Regulatory Proteins Contain Structural Motifs That Can Read DNA Sequences
[View]The Helix-Turn-Helix Motif Is One of the Simplest and Most Common DNA-binding Motifs
[View]Homeodomain Proteins Are a Special Class of Helix-Turn-Helix Proteins
[View]There Are Several Types of DNA-binding Zinc Finger Motifs
[View]Beta Sheets Can Also Recognize DNA
[View]The Leucine Zipper Motif Mediates Both DNA Binding and Protein Dimerization
[View]The Helix-Loop-Helix Motif Also Mediates Dimerization and DNA Binding
[View]It Is Not Yet Possible to Predict the DNA Sequence Recognized by a Gene Regulatory Protein
[View]A Gel-Mobility Shift Assay Allows Sequence-specific DNA-binding Proteins to Be Detected Readily
[View]DNA Affinity Chromatography Facilitates the Purification of Sequence-specific DNA-binding Proteins
[View]Summary
[View]Introduction
[View]The Tryptophan Repressor Is a Simple Switch That Turns Genes On and Off in Bacteria
[View]Transcriptional Activators Turn Genes On
[View]A Transcriptional Activator and a Transcriptional Repressor Control the lac Operon
[View]Regulation of Transcription in Eucaryotic Cells Is Complex
[View]Eucaryotic RNA Polymerase Requires General Transcription Factors
[View]Enhancers Control Genes at a Distance
[View]A Eucaryotic Gene Control Region Consists of a Promoter Plus Regulatory DNA Sequences
[View]Many Gene Activator Proteins Accelerate the Assembly of General Transcription Factors
[View]Gene Repressor Proteins Can Inhibit Transcription in Various Ways
[View]Eucaryotic Gene Regulatory Proteins Often Assemble into Small Complexes on DNA
[View]Complex Genetic Switches That Regulate Drosophila Development Are Built Up from Smaller Modules
[View]The Drosophila eve Gene Is Regulated by Combinatorial Controls
[View]Complex Mammalian Gene Control Regions Are Also Constructed from Simple Regulatory Modules
[View]The Activity of a Gene Regulatory Protein Can Itself Be Regulated
[View]Bacteria Use Interchangeable RNA Polymerase Subunits to Help Regulate Gene Transcription
[View]Gene Switches Have Gradually Evolved
[View]Summary
[View]Introduction
[View]Transcription Can Be Activated on DNA That Is Packaged into Nucleosomes
[View]Some Forms of Chromatin Silence Transcription
[View]An Initial Decondensation Step May Be Required Before Mammalian Globin Genes Can Be Transcribed
[View]The Mechanisms That Form Active Chromatin Are Not Understood
[View]Superhelical Tension in DNA Allows Action at a Distance
[View]Summary
[View]Introduction
[View]DNA Rearrangements Mediate Phase Variation in Bacteria
[View]Several Gene Regulatory Proteins Determine Cell Type Identity in Yeasts
[View]Two Proteins That Repress Each Other's Synthesis Determine the Heritable State of Bacteriophage Lambda
[View]Expression of a Critical Gene Regulatory Protein Can Trigger Expression of a Whole Battery of Downstream Genes
[View]Combinatorial Gene Control Is the Norm in Eucaryotes
[View]An Inactive X Chromosome Is Inherited
[View]Drosophila and Yeast Genes Can Also Be Inactivated by Heritable Features of Chromatin Structure
[View]The Pattern of DNA Methylation Can Be Inherited When Vertebrate Cells Divide
[View]DNA Methylation Reinforces Developmental Decisions in Vertebrate Cells
[View]Genomic Imprinting Requires DNA Methylation
[View]CG-rich Islands Are Associated with About 40,000 Genes in Mammals
[View]Summary
[View]Introduction
[View]Transcription Attenuation Causes the Premature Termination of Some RNA Molecules
[View]Alternative RNA Splicing Can Produce Different Forms of a Protein from the Same Gene
[View]Sex Determination in Drosophila Depends on a Regulated Series of RNA Splicing Events
[View]A Change in the Site of RNA Transcript Cleavage and Poly-A Addition Can Change the Carboxyl Terminus of a Protein
[View]The Definition of a Gene Has Had to Be Modified Since the Discovery of Alternative RNA Splicing
[View]RNA Transport from the Nucleus Can Be Regulated
[View]Some mRNAs Are Localized to Specific Regions of the Cytoplasm
[View]RNA Editing Can Change the Meaning of the RNA Message
[View]Procaryotic and Eucaryotic Cells Use Different Strategies to Specify the Translation Start Site on an mRNA Molecule
[View]The Phosphorylation of an Initiation Factor Regulates Protein Synthesis
[View]Proteins That Bind to the 5' Leader Region of mRNAs Mediate Negative Translational Control
[View]Gene Expression Can Be Controlled by a Change in mRNA Stability
[View]Selective mRNA Degradation Is Coupled to Translation
[View]Cytoplasmic Control of Poly-A Length Can Affect Translation in Addition to mRNA Stability
[View]A Few mRNAs Contain a Recoding Signal That Interrupts the Normal Course of Translation
[View]RNA-catalyzed Reactions in Cells Are Likely to Be of Extremely Ancient Origin
[View]Summary
10:Membrane Structure
[View]Introduction
[View]Membrane Lipids Are Amphipathic Molecules, Most of Which Spontaneously Form Bilayers
[View]The Lipid Bilayer Is a Two-dimensional Fluid
[View]The Fluidity of a Lipid Bilayer Depends on Its Composition
[View]The Lipid Bilayer Is Asymmetrical
[View]Glycolipids Are Found on the Surface of All Plasma Membranes
[View]Summary
[View]Introduction
[View]Membrane Proteins Can Be Associated with the Lipid Bilayer in Various Ways
[View]In Most Transmembrane Proteins the Polypeptide Chain Is Thought to Cross the Lipid Bilayer in an Alpha-helical Conformation
[View]Membrane Proteins Can Be Solubilized and Purified in Detergents
[View]The Cytoplasmic Side of Membrane Proteins Can Be Readily Studied in Red Blood Cell Ghosts
[View]Spectrin Is a Cytoskeletal Protein Noncovalently Associated with the Cytoplasmic Side of the Red Blood Cell Membrane
[View]Glycophorin Extends Through the Red Blood Cell Lipid Bilayer as a Single Alpha Helix
[View]Band 3 of the Red Blood Cell Is a Multipass Membrane Protein That Catalyzes the Coupled Transport of Anions
[View]Bacteriorhodopsin Is a Proton Pump That Traverses the Lipid Bilayer as Seven a Helices
[View]Porins Are Pore-forming Transmembrane Proteins That Cross the Lipid Bilayer as a Beta Barrel
[View]Membrane Proteins Often Function as Large Complexes
[View]Many Membrane Proteins Diffuse in the Plane of the Membrane
[View]Cells Can Confine Proteins and Lipids to Specific Domains Within a Membrane
[View]The Cell Surface Is Coated with Sugar Residues
[View]Selectins Are Cell-Surface Carbohydrate-binding Proteins That Mediate Transient Cell-Cell Adhesions in the Bloodstream
[View]Summary
11:Membrane Transport of Small Molecules and the Ionic Basis of Membrane Excitability
[View]Introduction
[View]Protein-free Lipid Bilayers Are Highly Impermeable to Ions
[View]There Are Two Main Classes of Membrane Transport Proteins - Carriers and Channels
[View]Active Transport Is Mediated by Carrier Proteins Coupled to an Energy Source
[View]Recombinant DNA Technology Has Revolutionized the Study of Membrane Transport Proteins
[View]Ionophores Can Be Used as Tools to Increase the Permeability of Membranes to Specific Ions
[View]Summary
[View]Introduction
[View]The Plasma Membrane Na⁺-K⁺ Pump Is an ATPase
[View]The Na⁺-K⁺ ATPase Is Required to Maintain Osmotic Balance and Stabilize Cell Volume
[View]Some Ca²⁺ Pumps Are Also Membrane-bound ATPases
[View]Membrane-bound Enzymes That Synthesize ATP Are Transport ATPases Working in Reverse
[View]Active Transport Can Be Driven by Ion Gradients
[View]Na⁺-driven Carrier Proteins in the Plasma Membrane Regulate Cytosolic pH
[View]An Asymmetrical Distribution of Carrier Proteins in Epithelial Cells Underlies the Transcellular Transport of Solutes
[View]Some Bacterial Transport ATPases Are Homologous to Eucaryotic Transport ATPases Involved in Drug Resistance and Cystic Fibrosis: The ABC Transporter Superfamily
[View]Summary
[View]Introduction
[View]Ion Channels Are Ion Selective and Fluctuate Between Open and Closed States
[View]The Membrane Potential in Animal Cells Depends Mainly on K⁺ Leak Channels and the K⁺ Gradient Across the Plasma Membrane
[View]The Resting Potential Decays Only Slowly When the Na⁺-K⁺ Pump Is Stopped
[View]The Function of a Nerve Cell Depends on Its Elongated Structure
[View]Voltage-gated Cation Channels Are Responsible for the Generation of Action Potentials in Electrically Excitable Cells
[View]Myelination Increases the Speed and Efficiency of Action Potential Propagation in Nerve Cells
[View]Patch-Clamp Recording Indicates That Individual Na⁺ Channels Open in an All-or-Nothing Fashion
[View]Voltage-gated Cation Channels Are Evolutionarily and Structurally Related
[View]Transmitter-gated Ion Channels Convert Chemical Signals into Electrical Ones at Chemical Synapses
[View]Chemical Synapses Can Be Excitatory or Inhibitory
[View]The Acetylcholine Receptors at the Neuromuscular Junction Are Transmitter-gated Cation Channels
[View]Transmitter-gated Ion Channels Are Major Targets for Psychoactive Drugs
[View]Neuromuscular Transmission Involves the Sequential Activation of Five Different Sets of Ion Channels
[View]The Grand Postsynaptic Potential in a Neuron Represents a Spatial and Temporal Summation of Many Small Postsynaptic Potentials
[View]Neuronal Computation Requires a Combination of At Least Three Kinds of K⁺ Channels
[View]Long-term Potentiation in the Mammalian Hippocampus Depends on Ca²⁺ Entry Through NMDA-Receptor Channels
[View]Summary
12:Intracellular Compartments and Protein Sorting
[View]Introduction
[View]All Eucaryotic Cells Have the Same Basic Set of Membrane-bounded Organelles
[View]The Topological Relationships of Membrane-bounded Organelles Can Be Interpreted in Terms of Their Evolutionary Origins
[View]Proteins Can Move Between Compartments in Different Ways
[View]Signal Peptides and Signal Patches Direct Proteins to the Correct Cellular Address
[View]Cells Cannot Construct Their Membrane-bounded Organelles de Novo: They Require Information in the Organelle Itself
[View]Summary
[View]Introduction
[View]Nuclear Pores Perforate the Nuclear Envelope
[View]Nuclear Localization Signals Direct Nuclear Proteins to the Nucleus
[View]Macromolecules Are Actively Transported into and out of the Nucleus Through Nuclear Pores
[View]The Nuclear Envelope Is Disassembled During Mitosis
[View]Transport Between Nucleus and Cytosol Can Be Regulated by Preventing Access to the Transport Machinery
[View]Summary
[View]Introduction
[View]Translocation into the Mitochondrial Matrix Depends on a Matrix Targeting Signal
[View]Translocation into the Mitochondrial Matrix Requires Both the Electrochemical Gradient Across the Inner Membrane and ATP Hydrolysis
[View]Mitochondrial Proteins Are Imported into the Matrix in a Two-Stage Process at Contact Sites That Join the Inner and Outer Membranes
[View]Proteins Are Imported into the Mitochondrial Matrix in an Unfolded State
[View]Sequential Binding of the Imported Protein to Mitochondrial hsp70 and hsp60 Drives Its Translocation and Assists Protein Folding
[View]Protein Transport into the Mitochondrial Inner Membrane and the Intermembrane Space Requires Two Signals
[View]Two Signal Peptides Are Required to Direct Proteins to the Thylakoid Membrane in Chloroplasts
[View]Summary
[View]Introduction
[View]Peroxisomes Use Molecular Oxygen and Hydrogen Peroxide to Carry Out Oxidative Reactions
[View]A Short Signal Sequence Directs the Import of Proteins into Peroxisomes
[View]Summary
[View]Introduction
[View]Membrane-bound Ribosomes Define the Rough ER
[View]Smooth ER Is Abundant in Some Specialized Cells
[View]Rough and Smooth Regions of ER Can Be Separated by Centrifugation
[View]Signal Peptides Were First Discovered in Proteins Imported into the Rough ER
[View]A Signal-Recognition Particle (SRP) Directs ER Signal Peptides to a Specific Receptor in the Rough ER Membrane
[View]Translocation Across the ER Membrane Does Not Always Require Ongoing Polypeptide Chain Elongation
[View]The Polypeptide Chain Passes Through an Aqueous Pore in the Translocation Apparatus
[View]The ER Signal Peptide Is Removed from Most Soluble Proteins After Translocation
[View]In Single-Pass Transmembrane Proteins a Single Internal ER Signal Peptide Remains in the Lipid Bilayer as a Membrane-spanning a Helix
[View]Combinations of Start- and Stop-Transfer Signals Determine the Topology of Multipass Transmembrane Proteins
[View]Translocated Polypeptide Chains Fold and Assemble in the Lumen of the Rough ER
[View]Most Proteins Synthesized in the Rough ER Are Glycosylated by the Addition of a Common N-linked Oligosaccharide
[View]Some Membrane Proteins Exchange a Carboxyl-Terminal Transmembrane Tail for a Covalently Attached Glycosylphosphatidylinositol (GPI) Anchor After Entry into the ER
[View]Most Membrane Lipid Bilayers Are Assembled in the ER
[View]Phospholipid Exchange Proteins Help Transport Phospholipids from the ER to Mitochondria and Peroxisomes
[View]Summary
13:Vesicular Traffic in the Secretory and Endocytic Pathways
[View]Introduction
[View]The Golgi Apparatus Consists of an Ordered Series of Compartments
[View]ER-Resident Proteins Are Selectively Retrieved from the Cis Golgi Network
[View]Golgi Proteins Return to the ER When Cells Are Treated with the Drug Brefeldin A
[View]Oligosaccharide Chains Are Processed in the Golgi Apparatus
[View]The Golgi Cisternae Are Organized as a Series of Processing Compartments
[View]Proteoglycans Are Assembled in the Golgi Apparatus
[View]The Carbohydrate in Cell Membranes Faces the Side of the Membrane That Is Topologically Equivalent to the Outside of the Cell
[View]What Is the Purpose of Glycosylation?
[View]Summary
[View]Introduction
[View]Lysosomes Are the Principal Sites of Intracellular Digestion
[View]Lysosomes Are Heterogeneous
[View]Plant and Fungal Vacuoles Are Remarkably Versatile Lysosomes
[View]Materials Are Delivered to Lysosomes by Multiple Pathways
[View]Some Cytosolic Proteins Are Directly Transported into Lysosomes for Degradation
[View]Lysosomal Enzymes Are Sorted from Other Proteins in the Trans Golgi Network by a Membrane-bound Receptor Protein That Recognizes Mannose 6-Phosphate
[View]The Mannose 6-Phosphate Receptor Shuttles Back and Forth Between Specific Membranes
[View]A Signal Patch in the Polypeptide Chain Provides the Cue for Tagging a Lysosomal Enzyme with Mannose 6-Phosphate
[View]Defects in the GlcNAc Phosphotransferase Cause a Lysosomal Storage Disease in Humans
[View]Summary
[View]Introduction
[View]Specialized Phagocytic Cells Can Ingest Large Particles
[View]Pinocytic Vesicles Form from Coated Pits in the Plasma Membrane
[View]Clathrin-coated Pits Can Serve as a Concentrating Device for Internalizing Specific Extracellular Macromolecules
[View]Cells Import Cholesterol by Receptor-mediated Endocytosis
[View]Endocytosed Materials Often End Up in Lysosomes
[View]Specific Proteins Are Removed from Early Endosomes and Returned to the Plasma Membrane
[View]The Relationship Between Early and Late Endosomes Is Uncertain
[View]Macromolecules Can Be Transferred Across Epithelial Cell Sheets by Transcytosis
[View]Epithelial Cells Have Two Distinct Early Endosomal Compartments But a Common Late Endosomal Compartment
[View]Summary
[View]Introduction
[View]Many Proteins and Lipids Seem to Be Carried Automatically from the ER and Golgi Apparatus to the Cell Surface
[View]Secretory Vesicles Bud from the Trans Golgi Network
[View]Proteins Are Often Proteolytically Processed During the Formation of Secretory Vesicles
[View]Secretory Vesicles Wait Near the Plasma Membrane Until Signaled to Release Their Contents
[View]Regulated Exocytosis Is a Localized Response of the Plasma Membrane and Its Underlying Cytoplasm
[View]Secretory-Vesicle Membrane Components Are Recycled
[View]Synaptic Vesicles Form from Endosomes
[View]Polarized Cells Direct Proteins from the Trans Golgi Network to the Appropriate Domain of the Plasma Membrane
[View]Summary
[View]Introduction
[View]Maintenance of Differences Between Compartments Requires an Input of Free Energy
[View]There Is More Than One Type of Coated Vesicle
[View]The Assembly of a Clathrin Coat Drives Bud Formation
[View]Adaptins Recognize Specific Transmembrane Proteins and Link Them to the Clathrin Cage
[View]Coatomer-coated Vesicles Mediate Nonselective Vesicular Transport
[View]Vesicular Transport Depends on Regulatory GTP-binding Proteins
[View]ARF Seems to Signal the Assembly and Disassembly of the Coatomer Coat
[View]Organelle Marker Proteins Called SNAREs Help Guide Vesicular Transport
[View]Rab Proteins Are Thought to Ensure the Specificity of Vesicle Docking
[View]Vesicle Fusion Is Catalyzed by a "Membrane-Fusion Machine"
[View]The Best-characterized Membrane-Fusion Protein Is Made by a Virus
[View]Summary
14:Energy Conversion: Mitochondria and Chloroplasts
[View]Introduction
[View]The Mitochondrion Contains an Outer Membrane and an Inner Membrane That Create Two Internal Compartments
[View]Mitochondrial Oxidation Begins When Large Amounts of Acetyl CoAAre Produced in the Matrix Space from Fatty Acids and Pyruvate
[View]The Citric Acid Cycle Oxidizes the Acetyl Group on Acetyl CoA to Generate NADH and FADH₂ for the Respiratory Chain
[View]A Chemiosmotic Process Converts Oxidation Energy into ATP on the Inner Mitochondrial Membrane
[View]Electrons Are Transferred from NADH to Oxygen Through Three Large Respiratory Enzyme Complexes
[View]Energy Released by the Passage of Electrons Along the Respiratory Chain Is Stored as an Electrochemical Proton Gradient Across the Inner Membrane
[View]The Energy Stored in the Electrochemical Proton Gradient Is Used to Produce ATP and to Transport Metabolites and Inorganic Ions into the Matrix Space
[View]The Rapid Conversion of ADP to ATP in Mitochondria Maintains a High Ratio of ATP to ADP in Cells
[View]The Difference Between delta-G° and delta-G: A Large Negative Value of delta-G Is Required for ATP Hydrolysis to Be Useful to the Cell
[View]Cellular Respiration Is Remarkably Efficient
[View]Summary
[View]Introduction
[View]Functional Inside-out Particles Can Be Isolated from Mitochondria
[View]ATP Synthase Can Be Purified and Added Back to Membranes
[View]ATP Synthase Can Function in Reverse to Hydrolyze ATP and Pump H⁺
[View]The Respiratory Chain Pumps H⁺ Across the Inner Mitochondrial Membrane
[View]Spectroscopic Methods Have Been Used to Identify Many Electron Carriers in the Respiratory Chain
[View]The Respiratory Chain Contains Three Large Enzyme Complexes Embedded in the Inner Membrane
[View]An Iron-Copper Center in Cytochrome Oxidase Catalyzes Efficient O₂ Reduction
[View]Electron Transfers Are Mediated by Random Collisions Between Diffusing Donors and Acceptors in the Mitochondrial Inner Membrane
[View]A Large Drop in Redox Potential Across Each of the Three Respiratory Enzyme Complexes Provides the Energy for H⁺ Pumping
[View]The Mechanism of H⁺ Pumping Is Best Understood in Bacteriorhodopsin
[View]H⁺ Ionophores Dissipate the H⁺ Gradient and Thereby Uncouple Electron Transport from ATP Synthesis
[View]Respiratory Control Normally Restrains Electron Flow Through the Chain
[View]Natural Uncouplers Convert the Mitochondria in Brown Fat into Heat-generating Machines
[View]All Bacteria Use Chemiosmotic Mechanisms to Harness Energy
[View]Summary
[View]Introduction
[View]The Chloroplast Is One Member of a Family of Organelles That Is Unique to Plants - the Plastids
[View]Chloroplasts Resemble Mitochondria But Have an Extra Compartment
[View]Two Unique Reactions in Chloroplasts: The Light-driven Production of ATP and NADPH and the Conversion of CO₂ to Carbohydrate
[View]Carbon Fixation Is Catalyzed by Ribulose Bisphosphate Carboxylase
[View]Three Molecules of ATP and Two Molecules of NADPH Are Consumed for Each CO₂ Molecule That Is Fixed in the Carbon-Fixation Cycle
[View]Carbon Fixation in Some Plants Is Compartmentalized to Facilitate Growth at Low CO₂ Concentrations
[View]Photosynthesis Depends on the Photochemistry of Chlorophyll Molecules
[View]A Photosystem Contains a Reaction Center Plus an Antenna Complex
[View]In a Reaction Center, Light Energy Captured by Chlorophyll Creates a Strong Electron Donor from a Weak One
[View]In Plants and Cyanobacteria Noncyclic Photophosphorylation Produces Both NADPH and ATP
[View]Chloroplasts Can Make ATP by Cyclic Photophosphorylation Without Making NADPH
[View]The Electrochemical Proton Gradient Is Similar in Mitochondria and Chloroplasts
[View]Like the Mitochondrial Inner Membrane, the Chloroplast Inner Membrane Contains Carrier Proteins That Facilitate Metabolite Exchange with the Cytosol
[View]Chloroplasts Carry Out Other Biosyntheses
[View]Summary
[View]Introduction
[View]The Earliest Cells Probably Produced ATP by Fermentation
[View]The Evolution of Energy-conserving Electron-transport Chains Enabled Anaerobic Bacteria to Use Non-fermentable Organic Compounds as a Source of Energy
[View]By Providing an Inexhaustible Source of Reducing Power, Photosynthetic Bacteria Overcame a Major Obstacle in the Evolution of Cells
[View]The More Complex Photosynthetic Electron-Transport Chains of Cyanobacteria Produced Atmospheric Oxygen and Permitted New Life Forms
[View]Summary
[View]Introduction
[View]The Biosynthesis of Mitochondria and Chloroplasts Involves the Contribution of Two Separate Genetic Systems
[View]Organelle Growth and Division Maintain the Number of Mitochondria and Chloroplasts in a Cell
[View]The Genomes of Chloroplasts and Mitochondria Are Usually Circular DNA Molecules
[View]Mitochondria and Chloroplasts Contain Complete Genetic Systems
[View]The Chloroplast Genome of Higher Plants Contains About 120 Genes
[View]Mitochondrial Genomes Have Several Surprising Features
[View]Animal Mitochondria Contain the Simplest Genetic Systems Known
[View]Why Are Plant Mitochondrial Genomes So Large?
[View]Some Organelle Genes Contain Introns
[View]Mitochondrial Genes Can Be Distinguished from Nuclear Genes by Their Non-Mendelian (Cytoplasmic) Inheritance
[View]Organelle Genes Are Maternally Inherited in Many Organisms
[View]Petite Mutants in Yeasts Demonstrate the Overwhelming Importance of the Cell Nucleus for Mitochondrial Biogenesis
[View]Mitochondria and Chloroplasts Contain Tissue-specific Proteins
[View]Mitochondria Import Most of Their Lipids; Chloroplasts Make Most of Theirs
[View]Both Mitochondria and Chloroplasts Probably Evolved from Endosymbiotic Bacteria
[View]Why Do Mitochondria and Chloroplasts Have Their Own Genetic Systems?
[View]Summary
15:Cell Signaling
[View]Introduction
[View]Extracellular Signaling Molecules Are Recognized by Specific Receptors on or in Target Cells
[View]Secreted Molecules Mediate Three Forms of Signaling: Paracrine, Synaptic, and Endocrine
[View]Autocrine Signaling Can Coordinate Decisions by Groups of Identical Cells
[View]Gap Junctions Allow Signaling Information to Be Shared by Neighboring Cells
[View]Each Cell Is Programmed to Respond to Specific Combinations of Signaling Molecules
[View]Different Cells Can Respond Differently to the Same Chemical Signal
[View]The Concentration of a Molecule Can Be Adjusted Quickly Only If the Lifetime of the Molecule Is Short
[View]Nitric Oxide Gas Signals by Binding Directly to an Enzyme Inside the Target Cell
[View]Steroid Hormones, Thyroid Hormones, Retinoids, and Vitamin D Bind to Intracellular Receptors That Are Ligand-activated Gene Regulatory Proteins
[View]There Are Three Known Classes of Cell-Surface Receptor Proteins: Ion-Channel-linked, G-Protein-linked, and Enzyme-linked
[View]Activated Cell-Surface Receptors Trigger Phosphate-Group Additions to a Network of Intracellular Proteins
[View]Summary
[View]Introduction
[View]Trimeric G Proteins Relay the Intracellular Signal from G-Protein-linked Receptors
[View]Some Receptors Increase Intracellular Cyclic AMP by Activating Adenylyl Cyclase via a Stimulatory G Protein (G_s)
[View]Trimeric G Proteins Are Thought to Disassemble When Activated
[View]Some Receptors Decrease Cyclic AMP by Inhibiting Adenylyl Cyclase via an Inhibitory Trimeric G Protein (G_i)
[View]Cyclic-AMP-dependent Protein Kinase (A-Kinase) Mediates the Effects of Cyclic AMP
[View]Serine/Threonine Protein Phosphatases Rapidly Reverse the Effects of A-Kinase
[View]To Use Ca²⁺ as an Intracellular Signal, Cells Must Keep Resting Cytosolic Ca²⁺ Levels Low
[View]Ca²⁺ Functions as a Ubiquitous Intracellular Messenger
[View]Some G-Protein-linked Receptors Activate the Inositol Phospholipid Signaling Pathway by Activating Phospholipase C-Beta
[View]Inositol Trisphosphate (IP₃) Couples Receptor Activation to Ca²⁺ Release from the ER
[View]Ca²⁺ Oscillations Often Prolong the Initial IP₃-induced Ca²⁺ Response
[View]Diacylglycerol Activates Protein Kinase C (C-Kinase)
[View]Calmodulin Is a Ubiquitous Intracellular Ca²⁺ Receptor
[View]Ca²⁺/Calmodulin-dependent Protein Kinases (CaM-Kinases) Mediate Most of the Actions of Ca²⁺ in Animal Cells
[View]The Cyclic AMP and Ca²⁺ Pathways Interact
[View]Some Trimeric G Proteins Directly Regulate Ion Channels
[View]Smell and Vision Depend on G-Protein-linked Receptors and Cyclic-Nucleotide-gated Ion Channels
[View]Extracellular Signals Are Greatly Amplified by the Use of Intracellular Mediators and Enzymatic Cascades
[View]Cells Can Respond Suddenly to a Gradually Increasing Concentration of an Extracellular Signal
[View]The Effect of Some Signals Can Be Remembered by the Cell
[View]Summary
[View]Introduction
[View]Receptor Guanylyl Cyclases Generate Cyclic GMP Directly
[View]The Receptors for Most Growth Factors Are Transmembrane Tyrosine-specific Protein Kinases
[View]Phosphorylated Tyrosine Residues Are Recognized by Proteins with SH2 Domains
[View]The Ras Proteins Provide a Crucial Link in the Intracellular Signaling Cascades Activated by Receptor Tyrosine Kinases
[View]An SH Adaptor Protein Couples Receptor Tyrosine Kinases to Ras: Evidence from the Developing Drosophila Eye
[View]Ras Activates a Serine/Threonine Phosphorylation Cascade That Activates MAP-Kinase
[View]Tyrosine-Kinase-associated Receptors Depend on Nonreceptor Tyrosine Kinases for Their Activity
[View]Some Receptors Are Protein Tyrosine Phosphatases
[View]Cancer-promoting Oncogenes Have Helped Identify Many Components in the Receptor Tyrosine Kinase Signaling Pathways
[View]Proteins in the TGF-beta Superfamily Activate Receptors That Are Serine/Threonine Protein Kinases
[View]The Notch Transmembrane Receptor Mediates Lateral Inhibition by an Unknown Mechanism
[View]Summary
[View]Introduction
[View]Slow Adaptation Depends on Receptor Down-Regulation
[View]Rapid Adaptation Often Involves Receptor Phosphorylation
[View]Some Forms of Adaptation Are Due to Downstream Changes
[View]Adaptation Plays a Crucial Role in Bacterial Chemotaxis
[View]Bacterial Chemotaxis Is Mediated by a Family of Four Homologous Transmembrane Receptors and a Phosphorylation Relay System
[View]Receptor Methylation Is Responsible for Adaptation in Bacterial Chemotaxis
[View]Summary
[View]Introduction
[View]Computer-based Neural Networks Can Be Trained
[View]Cell Signaling Networks Can Be Viewed as Neural Networks Trained by Evolution
[View]Signaling Networks Enable Cells to Respond to Complex Patterns of Extracellular Signals
[View]Signaling Networks Are Robust
[View]Summary
16:The Cytoskeleton
[View]Introduction
[View]The Cytoplasm of a Eucaryotic Cell Is Spatially Organized by Actin Filaments, Microtubules, and Intermediate Filaments
[View]Dynamic Microtubules Emanate from the Centrosome
[View]The Microtubule Network Can Find the Center of the Cell
[View]Motor Proteins Use the Microtubule Network as a Scaffold to Position Membrane-bounded Organelles
[View]The Actin Cortex Can Generate and Maintain Cell Polarity
[View]Actin Filaments and Microtubules Usually Act Together to Polarize the Cell
[View]The Functions of the Cytoskeleton Are Difficult to Study
[View]Summary
[View]Introduction
[View]Intermediate Filaments Are Polymers of Fibrous Proteins
[View]Epithelial Cells Contain a Highly Diverse Family of Keratin Filaments
[View]Many Nonepithelial Cells Contain Their Own Distinctive Cytoplasmic Intermediate Filaments
[View]The Nuclear Lamina Is Constructed from a Special Class of Intermediate Filament Proteins - the Lamins
[View]Intermediate Filaments Provide Mechanical Stability to Animal Cells
[View]Summary
[View]Introduction
[View]Microtubules Are Hollow Tubes Formed from Tubulin
[View]Microtubules Are Highly Labile Structures That Are Sensitive to Specific Antimitotic Drugs
[View]Elongation of a Microtubule Is Rapid, Whereas the Nucleation of a New Microtubule Is Slow
[View]The Two Ends of a Microtubule Are Different and Grow at Different Rates
[View]Centrosomes Are the Primary Site of Nucleation of Microtubules in Animal Cells
[View]Microtubules Depolymerize and Repolymerize Continually in Animal Cells
[View]GTP Hydrolysis Can Explain the Dynamic Instability of Individual Microtubules
[View]The Dynamic Instability of Microtubules Provides an Organizing Principle for Cell Morphogenesis
[View]Microtubules Undergo a Slow "Maturation" Revealed by Posttranslational Modifications of Their Tubulin
[View]Microtubule-associated Proteins (MAPs) Bind to Microtubules and Modify Their Properties
[View]MAPs Help Create Functionally Differentiated Cytoplasm
[View]Kinesin and Dynein Direct Organelle Movement Along Microtubules
[View]The Rate and Direction of Movement Along a Microtubule Are Specified by the Head Domain of Motor Proteins
[View]Summary
[View]Introduction
[View]Cilia Move by the Bending of an Axoneme - a Complex Bundle of Microtubules
[View]Dynein Drives the Movements of Cilia and Flagella
[View]Flagella and Cilia Grow from Basal Bodies That Are Closely Related to Centrioles
[View]Centrioles Usually Arise by the Duplication of Preexisting Centrioles
[View]Summary
[View]Introduction
[View]Actin Filaments Are Thin and Flexible
[View]Actin and Tubulin Polymerize by Similar Mechanisms
[View]ATP Hydrolysis Is Required for the Dynamic Behavior of Actin Filaments
[View]The Functions of Actin Filaments Are Inhibited by Both Polymer-stabilizing and Polymer-destabilizing Drugs
[View]The Actin Molecule Binds to Small Proteins That Help to Control Its Polymerization
[View]Many Cells Extend Dynamic Actin-containing Microspikes and Lamellipodia from Their Leading Edge
[View]The Leading Edge of Motile Cells Nucleates Actin Polymerization
[View]Some Pathogenic Bacteria Use Actin to Move Within and Between Cells
[View]Polymerization of Actin in the Cell Cortex Is Controlled by Cell-Surface Receptors
[View]Heterotrimeric G Proteins and Small GTPases Relay Signals from the Cell Surface to the Actin Cortex
[View]Mechanisms of Cell Polarization Can Be Analyzed in Yeast Cells
[View]Summary
[View]Introduction
[View]A Simple Membrane-attached Cytoskeleton Provides Mechanical Support to the Plasma Membrane of Erythrocytes
[View]Cross-linking Proteins with Different Properties Organize Particular Actin Assemblies
[View]Actin-binding Proteins with Different Properties Are Built Up from Similar Modules
[View]Gelsolin Fragments Actin Filaments in Response to Ca²⁺ Activation
[View]Multiple Types of Myosin Are Found in Eucaryotic Cells
[View]There Are Transient Musclelike Assemblies in Nonmuscle Cells
[View]Focal Contacts Allow Actin Filaments to Pull Against the Substratum
[View]Microvilli Illustrate How Bundles of Cross-linked Actin Filaments Can Stabilize Local Extensions of the Plasma Membrane
[View]The Behavior of the Cell Cortex Depends on a Balance of Cooperative and Competitive Interactions Among a Large Set of Actin-binding Proteins
[View]The Migration of Animal Cells Can Be Divided into Three Distinct Actin-dependent Subprocesses
[View]The Mechanism of Cell Locomotion Can Be Dissected Genetically
[View]Summary
[View]Introduction
[View]Myofibrils Are Composed of Repeating Assemblies of Thick and Thin Filaments
[View]Contraction Occurs as the Myosin and Actin Filaments Slide Past Each Other
[View]A Myosin Head "Walks" Toward the Plus End of an Actin Filament
[View]Muscle Contraction Is Initiated by a Sudden Rise in Cytosolic Ca²⁺
[View]Troponin and Tropomyosin Mediate the Ca²⁺ Regulation of Skeletal Muscle Contraction
[View]Other Accessory Proteins Maintain the Architecture of the Myofibril and Provide It with Elasticity
[View]The Same Contractile Machinery, in Modified Form, Is Found in Heart Muscle and Smooth Muscle
[View]The Activation of Myosin in Many Cells Depends on Myosin Light-Chain Phosphorylation
[View]Summary
17:The Cell-Division Cycle
[View]Introduction
[View]Replication of the Nuclear DNA Occurs During a Specific Part of Interphasethe S Phase
[View]Discrete Cell-Cycle Events Occur Against a Background of Continuous Growth
[View]A Central Control System Triggers the Essential Processes of the Cell Cycle
[View]The Cell-Cycle Control System Is a Protein-Kinase-based Machine
[View]Summary
[View]Introduction
[View]Growth of the Xenopus Oocyte Is Balanced by Cleavage of the Egg
[View]A Cytoplasmic Regulator, MPF, Controls Entry into Mitosis
[View]Oscillations in MPF Activity Control the Cell-Division Cycle
[View]Cyclin Accumulation and Destruction Control the Activation and Inactivation of MPF
[View]Degradation of Cyclin Triggers Exit from Mitosis
[View]MPF Can Act Autocatalytically to Stimulate Its Own Activation
[View]Active MPF Induces the Downstream Events of Mitosis
[View]The Cell-Cycle Control System Allows Time for One Round of DNA Replication in Each Interphase
[View]A Re-replication Block Ensures That No Segment of DNA Is Replicated More Than Once in a Cell Cycle
[View]Passage Through Mitosis Removes the Re-replication Block
[View]Summary
[View]Introduction
[View]Cell Growth Requires a Prolonged Interphase with Cell-Cycle Checkpoints
[View]Fission and Budding Yeasts Change Their Shape as They Progress Around the Cell Cycle
[View]Cell-Division-Cycle Mutations Halt the Cycle at Specific Points; wee Mutations Let the Cycle Skip Past a Size Checkpoint
[View]The Subunits of MPF in Yeasts Are Homologous to Those of MPF in Animals
[View]MPF Activity Is Regulated by Phosphorylation and Dephosphorylation
[View]The MPF-Activation Mechanism Controls Size in Fission Yeast
[View]For Most Cells the Major Cell-Cycle Checkpoint Is in G₁ at Start
[View]The Cdc2 Protein Associates with G₁ Cyclins to Drive a Cell Past Start
[View]The G₁ Cyclins Mediate Multiple Controls That Operate at Start
[View]Start Kinase Triggers Production of Components Required for DNA Replication
[View]Feedback Controls Ensure That Cells Complete One Cell-Cycle Process Before They Start the Next
[View]Damaged DNA Generates a Signal to Delay Mitosis
[View]Feedback Controls in the Cell Cycle Generally Depend on Inhibitory Signals
[View]Summary
[View]Introduction
[View]The Mammalian Cell-Cycle Control System Is More Elaborate Than That of the Yeast
[View]The Regulation of Mammalian Cell Growth and Proliferation Is Commonly Studied in Cultured Cell Lines
[View]Growth Factors Stimulate the Proliferation of Mammalian Cells
[View]Cell Growth and Cell Division Can Be Independently Regulated
[View]Cells Can Delay Division by Entering a Specialized Nongrowing State
[View]Serum Deprivation Prevents Passage Through the G₁ Checkpoint
[View]The Cell-Cycle Control System Can Be Rapidly Disassembled But Only Slowly Reassembled
[View]Neighboring Cells Compete for Growth Factors
[View]Normal Animal Cells in Culture Need Anchorage in Order to Pass Start
[View]Studies of Cancer Cells Reveal Genes Involved in the Control of Cell Proliferation
[View]Growth Factors Trigger Cascades of Intracellular Signals
[View]Cyclins and Cdk Are Induced by Growth Factor After a Long Delay
[View]The Retinoblastoma Protein Acts to Hold Proliferation in Check
[View]The Probability of Entering G₀ Increases with the Number of Times That a Cell Divides: Cell Senescence
[View]Intricately Regulated Patterns of Cell Division Generate and Maintain the Body
[View]Summary
18:The Mechanics of Cell Division
[View]Introduction
[View]Three Features Are Unique to M Phase: Chromosome Condensation, the Mitotic Spindle, and the Contractile Ring
[View]Cell Division Depends on the Duplication of the Centrosome
[View]M Phase Is Traditionally Divided into Six Stages
[View]Large Cytoplasmic Organelles Are Fragmented During M Phase to Ensure That They Are Faithfully Inherited
[View]Summary
[View]Introduction
[View]Formation of the Mitotic Spindle in an M-Phase Cell Is Accompanied by Striking Changes in the Dynamic Properties of Microtubules
[View]Interactions Between Oppositely Oriented Microtubules Drive Spindle Assembly
[View]Replicated Chromosomes Attach to Microtubules by Their Kinetochores
[View]Kinetochore Protein Complexes Assemble on Specific Centromeric DNA Sequences in Yeast Chromosomes
[View]Kinetochores Capture Microtubules Nucleated by the Spindle Poles
[View]The Plus Ends of Kinetochore Microtubules Can Add and Lose Tubulin Subunits While Attached to the Kinetochore
[View]Spindle Poles Repel Chromosomes
[View]Sister Chromatids Attach by Their Kinetochores to Opposite Spindle Poles
[View]Balanced Bipolar Forces Hold Chromosomes on the Metaphase Plate
[View]Microtubules Are Dynamic in the Metaphase Spindle
[View]Sister Chromatids Separate Suddenly at Anaphase
[View]Anaphase Is Delayed Until All Chromosomes Are Positioned at the Metaphase Plate
[View]Two Distinct Processes Separate Sister Chromatids at Anaphase
[View]Kinetochore Microtubules Disassemble During Anaphase A
[View]Two Separate Forces May Contribute to Anaphase B
[View]At Telophase the Nuclear Envelope Initially Re-forms Around Individual Chromosomes
[View]Summary
[View]Introduction
[View]The Mitotic Spindle Determines the Site of Cytoplasmic Cleavage During Cytokinesis
[View]The Spindle Is Specifically Repositioned to Create Asymmetric Cell Divisions
[View]Actin and Myosin Generate the Forces for Cleavage
[View]In Special Cases, Selected Cell Components Can Be Segregated to One Daughter Cell Only
[View]Cytokinesis Occurs by a Special Mechanism in Higher Plant Cells
[View]A Cytoskeletal Framework Determines the Plane of Plant Cell Division
[View]The Elaborate M Phase of Higher Organisms Evolved Gradually from Procaryotic Fission Mechanisms
[View]Summary
19:Cell Junctions, Cell Adhesion, and the Extracellular Matrix
[View]Introduction
[View]Tight Junctions Form a Selective Permeability Barrier Across Epithelial Cell Sheets
[View]Anchoring Junctions Connect the Cytoskeleton of a Cell to Those of Its Neighbors or to the Extracellular Matrix
[View]Adherens Junctions Connect Bundles of Actin Filaments from Cell to Cell or from Cell to Extracellular Matrix
[View]Desmosomes Connect Intermediate Filaments from Cell to Cell; Hemidesmosomes Connect Them to the Basal Lamina
[View]Gap Junctions Allow Small Molecules to Pass Directly from Cell to Cell
[View]Gap-Junction Connexons Are Composed of Six Subunits
[View]Most Cells in Early Embryos Are Coupled by Gap Junctions
[View]The Permeability of Gap Junctions Is Regulated
[View]In Plants, Plasmodesmata Perform Many of the Same Functions as Gap Junctions
[View]Summary
[View]Introduction
[View]There Are Two Basic Ways in Which Animal Cells Assemble into Tissues
[View]Dissociated Vertebrate Cells Can Reassemble into Organized Tissues Through Selective Cell-Cell Adhesion
[View]The Cadherins Mediate Ca²⁺-dependent Cell-Cell Adhesion in Vertebrates
[View]Cadherins Mediate Cell-Cell Adhesion by a Homophilic Mechanism
[View]Ca²⁺-independent Cell-Cell Adhesion Is Mediated Mainly by Members of the Immunoglobulin Superfamily of Proteins
[View]Multiple Types of Cell-Surface Molecules Act in Parallel to Mediate Selective Cell-Cell and Cell-Matrix Adhesion
[View]Nonjunctional Contacts May Initiate Tissue-specific Cell-Cell Adhesions That Junctional Contacts Then Orient and Stabilize
[View]Summary
[View]Introduction
[View]The Extracellular Matrix Is Made and Oriented by the Cells Within It
[View]Glycosaminoglycan (GAG) Chains Occupy Large Amounts of Space and Form Hydrated Gels
[View]Hyaluronan Is Thought to Facilitate Cell Migration During Tissue Morphogenesis and Repair
[View]Proteoglycans Are Composed of GAG Chains Covalently Linked to a Core Protein
[View]Proteoglycans Can Regulate the Activities of Secreted Signaling Molecules
[View]GAG Chains May Be Highly Organized in the Extracellular Matrix
[View]Cell-Surface Proteoglycans Act as Co-Receptors
[View]Collagens Are the Major Proteins of the Extracellular Matrix
[View]Collagens Are Secreted with a Nonhelical Extension at Each End
[View]After Secretion Fibrillar Procollagen Molecules Are Cleaved to Collagen Molecules, Which Assemble into Fibrils
[View]Fibril-associated Collagens Help Organize the Fibrils
[View]Cells Help Organize the Collagen Fibrils They Secrete by Exerting Tension on the Matrix
[View]Elastin Gives Tissues Their Elasticity
[View]Fibronectin Is an Extracellular Adhesive Protein That Helps Cells Attach to the Matrix
[View]Multiple Forms of Fibronectin Are Produced by Alternative RNA Splicing
[View]Glycoproteins in the Matrix Help Define Cell Migration Pathways
[View]Type IV Collagen Molecules Assemble into a Sheetlike Meshwork to Help Form Basal Laminae
[View]Basal Laminae Are Composed Mainly of Type IV Collagen, Heparan Sulfate Proteoglycan, Laminin, and Entactin
[View]Basal Laminae Perform Diverse and Complex Functions
[View]The Degradation of Extracellular Matrix Components Is Tightly Controlled
[View]Summary
[View]Introduction
[View]Integrins Are Transmembrane Heterodimers
[View]Integrins Must Interact with the Cytoskeleton in Order to Bind Cells to the Extracellular Matrix
[View]Integrins Enable the Cytoskeleton and Extracellular Matrix to Communicate Across the Plasma Membrane
[View]Cells Can Regulate the Activity of Their Integrins
[View]Integrins Can Activate Intracellular Signaling Cascades
[View]Summary
[View]Introduction
[View]The Composition of the Cell Wall Depends on the Cell Type
[View]The Tensile Strength of the Cell Wall Allows Plant Cells to Develop Turgor Pressure
[View]The Cell Wall Is Built from Cellulose Microfibrils Interwoven with a Network of Polysaccharides and Proteins
[View]Microtubules Orient Cell-Wall Deposition
[View]Summary
20:Germ Cells and Fertilization
[View]Introduction
[View]In Multicellular Animals the Diploid Phase Is Complex and Long, the Haploid Simple and Fleeting
[View]Sexual Reproduction Gives a Competitive Advantage to Organisms in an Unpredictably Variable Environment
[View]Summary
[View]Introduction
[View]Meiosis Involves Two Nuclear Divisions Rather Than One
[View]Genetic Reassortment Is Enhanced by Crossing-over Between Homologous Nonsister Chromatids
[View]Meiotic Chromosome Pairing Culminates in the Formation of the Synaptonemal Complex
[View]Recombination Nodules Are Thought to Mediate Chromatid Exchanges
[View]Chiasmata Play an Important Part in Chromosome Segregation in Meiosis
[View]Pairing of the Sex Chromosomes Ensures That They Also Segregate
[View]Meiotic Division II Resembles a Normal Mitosis
[View]Summary
[View]Introduction
[View]An Egg Is the Only Cell in a Higher Animal That Is Able to Develop into a New Individual
[View]An Egg Is Highly Specialized for Independent Development, with Large Nutrient Reserves and an Elaborate Coat
[View]Eggs Develop in Stages
[View]Oocytes Grow to Their Large Size Through Special Mechanisms
[View]Summary
[View]Introduction
[View]Sperm Are Highly Adapted for Delivering Their DNA to an Egg
[View]Sperm Are Produced Continuously in Many Mammals
[View]Summary
[View]Introduction
[View]Binding to the Zona Pellucida Induces the Sperm to Undergo an Acrosomal Reaction
[View]The Egg Cortical Reaction Helps to Ensure That Only One Sperm Fertilizes the Egg
[View]A Transmembrane Fusion Protein in the Sperm Plasma Membrane Catalyzes Sperm-Egg Fusion
[View]The Sperm Provides a Centriole for the Zygote
[View]Summary
21:Cellular Mechanisms of Development
[View]Introduction
[View]The Polarity of the Amphibian Embryo Depends on the Polarity of the Egg
[View]Cleavage Produces Many Cells from One
[View]The Blastula Consists of an Epithelium Surrounding a Cavity
[View]Gastrulation Transforms a Hollow Ball of Cells into a Three-layered Structure with a Primitive Gut
[View]Gastrulation Movements Are Organized Around the Dorsal Lip of the Blastopore
[View]Active Changes of Cell Packing Provide a Driving Force for Gastrulation
[View]The Three Germ Layers Formed by Gastrulation Have Different Fates
[View]The Mesoderm on Either Side of the Body Axis Breaks Up into Somites from Which Muscle Cells Derive
[View]Changing Patterns of Cell Adhesion Molecules Regulate Morphogenetic Movements
[View]Embryonic Tissues Are Invaded in a Strictly Controlled Fashion by Migratory Cells
[View]The Vertebrate Body Plan Is First Formed in Miniature and Then Maintained as the Embryo Grows
[View]Summary
[View]Introduction
[View]Initial Differences Among Xenopus Blastomeres Arise from the Spatial Segregation of Determinants in the Egg
[View]Inductive Interactions Generate New Types of Cells in a Progressively More Detailed Pattern
[View]A Simple Morphogen Gradient Can Organize a Complex Pattern of Cell Responses
[View]Cells Can React Differently to a Signal According to the Time When They Receive It: The Role of an Intracellular Clock
[View]In Mammals the Protected Uterine Environment Permits an Unusual Style of Early Development
[View]All the Cells of the Very Early Mammalian Embryo Have the Same Developmental Potential
[View]Mammalian Embryonic Stem Cells Show How Environmental Cues Can Control the Pace as well as the Pathway of Development
[View]Summary
[View]Introduction
[View]Cells Often Become Determined for a Future Specialized Role Long Before They Differentiate Overtly
[View]The Time of Cell Determination Can Be Discovered by Transplantation Experiments
[View]Cell Determination and Differentiation Reflect the Expression of Regulatory Genes
[View]The State of Determination May Be Governed by the Cytoplasm or Be Intrinsic to the Chromosomes
[View]Cells in Developing Tissues Remember Their Positional Values
[View]The Pattern of Positional Values Controls Cell Proliferation and Is Regulated by Intercalation
[View]Summary
[View]Introduction
[View]Caenorhabditis elegans Is Anatomically and Genetically Simple
[View]Nematode Development Is Almost Perfectly Invariant
[View]Developmental Control Genes Define the Rules of Cell Behavior That Generate the Body Plan
[View]Induction of the Vulva Depends on a Large Set of Developmental Control Genes
[View]Genetic and Microsurgical Tests Reveal the Logic of Developmental Control; Gene Cloning and Sequencing Help to Reveal Its Biochemistry
[View]Heterochronic Mutations Identify Genes That Specify Changes in the Rules of Cell Behavior as Time Goes By
[View]The Tempo of Development Is Not Controlled by the Cell-Division Cycle
[View]Cells Die Tidily as a Part of the Program of Development
[View]Summary
[View]Introduction
[View]The Insect Body Is Constructed by Modulation of a Fundamental Pattern of Repeating Units
[View]Drosophila Begins Its Development as a Syncytium
[View]Two Orthogonal Systems Define the Ground Plan of the Embryo
[View]The Patterning of the Embryo Begins with Influences from the Cells Surrounding the Egg
[View]The Dorsoventral Axis Is Specified Inside the Embryo by a Gene Regulatory Protein with a Graded Intranuclear Concentration
[View]The Posterior System Specifies Germ Cells as well as Posterior Body Segments
[View]mRNA Localized at the Anterior Pole Codes for a Gene Regulatory Protein That Forms an Anterior Morphogen Gradient
[View]Three Classes of Segmentation Genes Subdivide the Embryo
[View]The Localized Expression of Segmentation Genes Is Regulated by a Hierarchy of Positional Signals
[View]The Product of One Segmentation Gene Controls the Expression of Another to Create a Detailed Pattern
[View]Egg-Polarity, Gap, and Pair-Rule Genes Create a Transient Pattern That Is Remembered by Other Genes
[View]Segment-Polarity Genes Label the Basic Subdivisions of Every Parasegment
[View]Summary
[View]Introduction
[View]The Homeotic Selector Genes of the Bithorax Complex and the Antennapedia Complex Specify the Differences Among Parasegments
[View]Homeotic Selector Genes Encode a System of Molecular Address Labels
[View]The Control Regions of the Homeotic Selector Genes Act as Memory Chips for Positional Information
[View]The Adult Fly Develops from a Set of Imaginal Discs That Carry Remembered Positional Information
[View]Homeotic Selector Genes Are Essential for the Memory of Positional Information in Imaginal Disc Cells
[View]The Homeotic Selector Genes and Segment-Polarity Genes Define Compartments of the Body
[View]Localized Expression of Specific Gene Regulatory Proteins Foreshadows the Production of Sensory Bristles
[View]Lateral Inhibition Regulates the Fine-grained Pattern of Differentiated Cell Types
[View]The Developmental Control Genes of Drosophila Have Homologues in Vertebrates
[View]Mammals Have Four Homologous HOM Complexes
[View]Hox Genes Specify Positional Values in Vertebrates as in Insects
[View]Subsets of Hox Genes Are Expressed in Order Along Two Orthogonal Axes in the Vertebrate Limb Bud
[View]Summary
[View]Introduction
[View]Embryonic Development Starts by Establishing a Root-Shoot Axis and Then Halts Inside the Seed
[View]The Repetitive Modules of a Plant Are Generated Sequentially by Meristems
[View]The Shaping of Each New Structure Depends on Oriented Cell Division and Expansion
[View]Each Plant Module Grows from a Microscopic Set of Primordia in a Meristem
[View]Long-range Hormonal Signals Coordinate Developmental Events in Separate Parts of the Plant
[View]Arabidopsis Serves as a Model Organism for Plant Molecular Genetics
[View]Homeotic Selector Genes Specify the Parts of a Flower
[View]Summary
[View]Introduction
[View]Stocks of Neurons Are Generated at the Outset of Neural Development and Are Not Subsequently Replenished
[View]The Time and Place of a Neuron's Birth Determine the Connections It Will Form
[View]Each Axon or Dendrite Extends by Means of a Growth Cone at Its Tip
[View]The Growth Cone Pilots the Developing Neurite Along a Precisely Defined Path in Vivo^81-84
[View]Target Tissues Release Neurotrophic Factors That Control Nerve Cell Growth and Survival
[View]The Positional Values of Neurons Guide the Formation of Orderly Neural Maps: The Doctrine of Neuronal Specificity
[View]Axons from Opposite Sides of the Retina Respond Differently to a Gradient of Repulsive Molecules in the Tectum
[View]Diffuse Patterns of Synaptic Connections Are Sharpened by Activity-dependent Synapse Elimination
[View]Experience Molds the Pattern of Synaptic Connections in the Brain
[View]Summary
22:Differentiated Cells and the Maintenance of Tissues
[View]Introduction
[View]Most Differentiated Cells Remember Their Essential Character Even in a Novel Environment
[View]The Differentiated State Can Be Modulated by a Cell's Environment
[View]Summary
[View]Introduction
[View]The Cells at the Center of the Lens of the Adult Eye Are Remnants of the Embryo
[View]Most Permanent Cells Renew Their Parts: The Photoreceptor Cells of the Retina
[View]Summary
[View]Introduction
[View]The Liver Functions as an Interface Between the Digestive Tract and the Blood
[View]Liver Cell Loss Stimulates Liver Cell Proliferation
[View]Regeneration Requires Coordinated Growth of Tissue Components
[View]Endothelial Cells Line All Blood Vessels
[View]New Endothelial Cells Are Generated by Simple Duplication of Existing Endothelial Cells
[View]New Capillaries Form by Sprouting
[View]Angiogenesis Is Controlled by Growth Factors Released by the Surrounding Tissues
[View]Summary
[View]Introduction
[View]Stem Cells Can Divide Without Limit and Give Rise to Differentiated Progeny
[View]Epidermal Stem Cells Lie in the Basal Layer
[View]Differentiating Epidermal Cells Synthesize a Sequence of Different Keratins as They Mature
[View]Epidermal Stem Cells Are a Subset of Basal Cells
[View]Basal Cell Proliferation Is Regulated According to the Thickness of the Epidermis
[View]Secretory Cells in the Epidermis Are Secluded in Glands That Have Their Own Population Kinetics
[View]Summary
[View]Introduction
[View]There Are Three Main Categories of White Blood Cells: Granulocytes, Monocytes, and Lymphocytes
[View]The Production of Each Type of Blood Cell in the Bone Marrow Is Individually Controlled
[View]Bone Marrow Contains Hemopoietic Stem Cells
[View]A Pluripotent Stem Cell Gives Rise to All Classes of Blood Cells
[View]The Number of Specialized Blood Cells Is Amplified by Divisions of Committed Progenitor Cells
[View]The Factors That Regulate Hemopoiesis Can Be Analyzed in Culture
[View]Erythropoiesis Depends on the Hormone Erythropoietin
[View]Multiple CSFs Influence the Production of Neutrophils and Macrophages
[View]Hemopoietic Stem Cells Depend on Contact with Cells Expressing the Steel Factor
[View]The Behavior of a Hemopoietic Cell Depends Partly on Chance
[View]Regulation of Cell Survival Is as Important as Regulation of Cell Proliferation
[View]Summary
[View]Introduction
[View]New Skeletal Muscle Cells Form by the Fusion of Myoblasts
[View]Muscle Cells Can Vary Their Properties by Changing the Protein Isoforms That They Contain
[View]Some Myoblasts Persist as Quiescent Stem Cells in the Adult
[View]Summary
[View]Introduction
[View]Fibroblasts Change Their Character in Response to Signals in the Extracellular Matrix
[View]The Extracellular Matrix May Influence Connective-Tissue Cell Differentiation by Affecting Cell Shape and Attachment
[View]Different Signaling Molecules Act Sequentially to Regulate Production of Fat Cells
[View]Bone Is Continually Remodeled by the Cells Within It
[View]Osteoblasts Secrete Bone Matrix, While Osteoclasts Erode It
[View]During Development, Cartilage Is Eroded by Osteoclasts to Make Way for Bone
[View]The Structure of the Body Is Stabilized by Its Connective-Tissue Framework and by the Selective Cohesion of Cells
[View]Summary
[View]Introduction
23:The Immune System
[View]Introduction
[View]B Lymphocytes Make Humoral Antibody Responses; T Lymphocytes Make Cell-mediated Immune Responses
[View]Lymphocytes Develop in Primary Lymphoid Organs and React with Foreign Antigens in Secondary Lymphoid Organs
[View]Cell-Surface Markers Make It Possible to Distinguish and Separate T and B Cells
[View]The Immune System Works by Clonal Selection
[View]Most Antigens Stimulate Many Different Lymphocyte Clones
[View]Most Lymphocytes Continuously Recirculate
[View]Immunological Memory Is Due to Clonal Expansion and Lymphocyte Maturation
[View]The Failure to Respond to Self Antigens Is Due to Acquired Immunological Tolerance
[View]Summary
[View]Introduction
[View]The Antigen-specific Receptors on B Cells Are Antibody Molecules
[View]B Cells Can Be Stimulated to Secrete Antibodies in a Culture Dish
[View]Antibodies Have Two Identical Antigen-binding Sites
[View]An Antibody Molecule Is Composed of Two Identical Light Chains and Two Identical Heavy Chains
[View]There Are Five Classes of Heavy Chains, Each with Different Biological Properties
[View]Antibodies Can Have Either k or l Light Chains, but Not Both
[View]The Strength of an Antibody-Antigen Interaction Depends on Both the Number of Antigen-binding Sites Occupied and the Affinity of Each Binding Site
[View]Antibodies Recruit Complement to Help Fight Bacterial Infections
[View]Summary
[View]Introduction
[View]Light and Heavy Chains Consist of Constant and Variable Regions
[View]The Light and Heavy Chains Each Contain Three Hypervariable Regions That Together Form the Antigen-binding Site
[View]The Light and Heavy Chains Are Folded into Repeating Similar Domains
[View]X-ray Diffraction Studies Have Revealed the Structure of Ig Domains and Antigen-binding Sites in Three Dimensions
[View]Summary
[View]Introduction
[View]Antibody Genes Are Assembled from Separate Gene Segments During B Cell Development
[View]Each V Region Is Encoded by More Than One Gene Segment
[View]Imprecise Joining of Gene Segments Greatly Increases the Diversity of V Regions
[View]Antigen-driven Somatic Hypermutation Fine-tunes Antibody Responses
[View]Antibody Gene-Segment Joining Is Regulated to Ensure That B Cells Are Monospecific
[View]When Stimulated by Antigen, B Cells Switch from Making a Membrane-bound Antibody to Making a Secreted Form of the Same Antibody
[View]B Cells Can Switch the Class of Antibody They Make
[View]Summary
[View]Introduction
[View]T Cell Receptors Are Antibodylike Heterodimers
[View]Different T Cell Responses Are Mediated by Distinct Classes of T Cells
[View]Summary
[View]Introduction
[View]There Are Two Principal Classes of MHC Molecules
[View]X-ray Diffraction Studies Reveal the Antigen-binding Site of MHC Proteins as well as the Bound Peptide
[View]Class I and Class II MHC Molecules Have Different Functions
[View]CD4 and CD8 Proteins Act as MHC-binding Co-Receptors on Helper and Cytotoxic T Cells, Respectively
[View]Summary
[View]Introduction
[View]Cytotoxic T Cells Recognize Fragments of Viral Proteins on the Surface of Virus-infected Cells
[View]MHC-encoded ABC Transporters Transfer Peptide Fragments from the Cytosol to the ER Lumen
[View]Cytotoxic T Cells Induce Infected Target Cells to Kill Themselves
[View]Summary
[View]Introduction
[View]Helper T Cells Recognize Fragments of Endocytosed Foreign Protein Antigens in Association with Class II MHC Proteins
[View]Helper T Cells Are Activated by Antigen-presenting Cells
[View]The T Cell Receptor Forms Part of a Large Signaling Complex in the Plasma Membrane
[View]Two Simultaneous Signals Are Required for Helper T Cell Activation
[View]Helper T Cells, Once Activated, Stimulate Themselves and Other T Cells to Proliferate by Secreting Interleukin-2⁴⁰
[View]Helper T Cells Are Required for Most B Cells to Respond to Antigen
[View]The Activation of B Cells by Helper T Cells Is Mediated by Both Membrane-bound and Secreted Signals
[View]Some Helper T Cells Help Activate Cytotoxic T Cells and Macrophages by Secreting Interleukins
[View]Summary
[View]Introduction
[View]Developing T Cells That Recognize Peptides in Association with Self MHC Molecules Are Positively Selected in the Thymus
[View]Developing T Cells That React Strongly with Self Peptides Bound to Self MHC Molecules Are Eliminated in the Thymus
[View]Some Allelic Forms of MHC Molecules Are Ineffective at Presenting Specific Antigens to T Cells: Immune Response (Ir) Genes
[View]The Role of MHC Proteins in Antigen Presentation to T Cells Provides an Explanation for Transplantation Reactions and MHC Polymorphism
[View]Immune Recognition Molecules Belong to an Ancient Superfamily
[View]Summary
24:Cancer
[View]Introduction
[View]Cancers Differ According to the Cell Type from Which They Derive
[View]Most Cancers Derive from a Single Abnormal Cell
[View]Most Cancers Are Probably Initiated by a Change in the Cell's DNA Sequence
[View]A Single Mutation Is Not Enough to Cause Cancer
[View]Cancers Develop in Slow Stages from Mildly Aberrant Cells
[View]Tumor Progression Involves Successive Rounds of Mutation and Natural Selection
[View]The Development of a Cancer Can Be Promoted by Factors That Do Not Alter the Cell's DNA Sequence
[View]Most Cancers Result from Avoidable Combinations of Environmental Causes
[View]The Search for Cancer Cures Is Hard but Not Hopeless
[View]Cancerous Growth Often Depends on Deranged Control of Cell Differentiation or Cell Death
[View]To Metastasize, Cancer Cells Must Be Able to Cross Basal Laminae
[View]Mutations That Increase the Mutation Rate Accelerate the Development of Cancer
[View]The Enhanced Mutability of Cancer Cells Helps Them Evade Destruction by Anticancer Drugs
[View]Summary
[View]Introduction
[View]Retroviruses Can Act as Vectors for Oncogenes That Transform Cell Behavior
[View]Retroviruses Pick Up Oncogenes by Accident
[View]A Retrovirus Can Transform a Host Cell by Inserting Its DNA Next to a Proto-oncogene of the Host
[View]Different Searches for the Genetic Basis of Cancer Converge on Disturbances in the Same Proto-oncogenes
[View]A Proto-oncogene Can Be Made Oncogenic in Many Ways
[View]The Actions of Oncogenes Can Be Assayed Singly and in Combination in Transgenic Mice
[View]Loss of One Copy of a Tumor Suppressor Gene Can Create a Hereditary Predisposition to Cancer
[View]Loss of the Retinoblastoma Tumor Suppressor Gene Plays a Part in Many Different Cancers
[View]DNA Tumor Viruses Activate the Cell's DNA Replication Machinery as Part of Their Strategy for Survival
[View]DNA Tumor Viruses Activate the Cell's Replication Machinery by Blocking the Action of Key Tumor Suppressor Genes
[View]Mutations of the p53 Gene Disable an Emergency Brake on Cell Proliferation and Lead to Genetic Instability
[View]Colorectal Cancers Develop Slowly Via a Succession of Visible Structural Changes
[View]Mutations Leading to Colorectal Cancer Can Be Identified by Scanning the Cancer Cells and by Studying Families Prone to the Cancer
[View]Genetic Deletions in Colorectal Cancer Cells Reveal Sites of Loss of Tumor Suppressor Genes
[View]The Steps of Tumor Progression Can Be Correlated with Specific Mutations
[View]Each Case of Cancer Is Characterized by Its Own Array of Genetic Lesions
[View]Summary