Оглавление
Stephen R. Bolsover. Cell Biology
Table of Contents
List of Tables
List of Illustrations
Guide
Pages
CELL BIOLOGY. A Short Course
PREFACE
ACKNOWLEDGMENTS
ABOUT THE COMPANION WEBSITE
SECTION 1. THE STRUCTURE OF THE CELL
1 A LOOK AT CELLS AND TISSUES
ONLY TWO TYPES OF CELL
Cell Division
VIRUSES
ORIGIN OF EUKARYOTIC CELLS
Example 1.1 Sterilization by Filtration
IN DEPTH 1.1 OUR ANCESTOR, THE ARCHAEON
CELL SPECIALIZATION IN ANIMALS
STEM CELLS AND TISSUE REPLACEMENT
THE CELL WALL
MICROSCOPES REVEAL CELL STRUCTURE
The Modern Light Microscope
The Transmission Electron Microscope
The Scanning Electron Microscope
FLUORESCENCE MICROSCOPY
Increasing the Resolution of Fluorescence Microscopes
Fluorescent Proteins
BrainBox 1.1 Osamu Shimomura, Martin Chalfie, and Roger Tsien
SUMMARY
FURTHER READING
REVIEW QUESTIONS
THOUGHT QUESTION
2 MEMBRANES AND ORGANELLES
BASIC PROPERTIES OF CELL MEMBRANES
ORGANELLES BOUNDED BY DOUBLE‐MEMBRANE ENVELOPES
The Nucleus
IN DEPTH 2.1 WATER, WATER (AND AQUAPORINS) EVERYWHERE
Example 2.1 DNA Destruction in the Cytosol
Mitochondria
ORGANELLES BOUNDED BY SINGLE MEMBRANES
Peroxisomes
Endoplasmic Reticulum
Golgi Apparatus
Lysosomes
Medical Relevance 2.1 Lysosomal Storage Disorders
THE CONNECTED CELL
Organelle Junctions
Cell Junctions
IN DEPTH 2.2 MY OLD MAM
Example 2.2 Gap Junctions Keep Eggs Healthy
SUMMARY
FURTHER READING
REVIEW QUESTIONS
THOUGHT QUESTION
SECTION 2. THE MOLECULAR BIOLOGY OF THE CELL
3 DNA STRUCTURE AND THE GENETIC CODE
THE STRUCTURE OF DNA
IN DEPTH 3.1 WE HAVE A SECOND GENOME IN OUR CELLS
The DNA Molecule Is a Double Helix
Hydrogen Bonds Form Between Base Pairs
DNA Strands Are Antiparallel
Example 3.1 Erwin Chargaff's Puzzling Data
The Two DNA Strands Are Complementary
DNA AS THE GENETIC MATERIAL
PACKAGING OF DNA MOLECULES INTO CHROMOSOMES. Eukaryotic Chromosomes and Chromatin Structure
Medical Relevance 3.1 Anti‐Viral Drugs for HIV
Prokaryotic Chromosomes
BrainBox 3.1 Marie Maynard Daly
Plasmids
IN DEPTH 3.2 DNA – A GORDIAN KNOT
Viruses
THE GENETIC CODE. Amino Acids and Proteins
Reading the Genetic Code
Amino Acid Names Are Abbreviated
The Code Is Degenerate but Unambiguous
Start and Stop Codons and the Reading Frame
The Code Is Nearly Universal
Missense Mutations
BrainBox 3.2 William Warrick Cardozo
Medical Relevance 3.2 Osteogenesis Imperfecta
SUMMARY
FURTHER READING
REVIEW QUESTIONS
THOUGHT QUESTION
4 DNA AS A DATA STORAGE MEDIUM
DNA REPLICATION
The DNA Replication Fork
PROTEINS OPEN UP THE DNA DOUBLE HELIX DURING REPLICATION
DnaA Protein
DnaB and DnaC Proteins
Single‐Stranded DNA‐Binding Proteins
BIOCHEMISTRY OF DNA REPLICATION
Medical Relevance 4.1 Inhibiting DNA Polymerase Fights Cancer
Example 4.1 The Meselson and Stahl Experiment
DNA Synthesis Requires an RNA Primer
RNA Primers Are Removed
The Self‐Correcting DNA Polymerase
Mismatch Repair Backs Up the Proofreading Mechanism
DNA REPAIR AFTER REPLICATION
Spontaneous and Chemically Induced Base Changes
Repair Processes
GENE STRUCTURE AND ORGANIZATION IN EUKARYOTES. Introns and Exons – Additional Complexity in Eukaryotic Genes
Medical Relevance 4.2 Bloom's Syndrome and Xeroderma Pigmentosum
The Major Classes of Eukaryotic DNA
IN DEPTH 4.1 THERE ARE MORE PROTEINS THAN GENES IN MULTI‐CELLULAR ORGANISMS
GENE NOMENCLATURE
IN DEPTH 4.2 GENOME PROJECTS
BrainBox 4.1 Elizabeth Blackburn, Carol Greider, and Jack Szostak
SUMMARY
FURTHER READING
REVIEW QUESTIONS
THOUGHT QUESTION
5 TRANSCRIPTION AND THE CONTROLOF GENE EXPRESSION
STRUCTURE OF RNA
RNA POLYMERASE
GENE NOTATION
BACTERIAL RNA SYNTHESIS
CONTROL OF BACTERIAL GENE EXPRESSION
Lac, an Inducible Operon
Example 5.1 Quorum Sensing: Squid That Glow in the Dark
Trp, a Repressible Operon
EUKARYOTIC RNA SYNTHESIS
Messenger RNA Processing in Eukaryotes
CONTROL OF EUKARYOTIC GENE EXPRESSION
Glucocorticoids Cross the Plasma Membrane to Activate Transcription
Medical Relevance 5.1 Aldosterone in the Kidney
Medical Relevance 5.2 The Glucocorticoid Receptor, Inflammation, and COVID‐19
NONCODING RNAs AND THE CONTROL OF EUKARYOTIC GENE EXPRESSION
Micro RNAs
Long Noncoding RNAs
Circular RNAs
SUMMARY
FURTHER READING
REVIEW QUESTIONS
THOUGHT QUESTION
6 MANUFACTURING PROTEIN
ATTACHMENT OF AN AMINO ACID TO ITS tRNA
Transfer RNA, the Anticodon, and Wobble
IN DEPTH 6.1 HOW WE SEPARATE PROTEINS IN ONE DIMENSION
THE RIBOSOME
BACTERIAL PROTEIN SYNTHESIS. Ribosome‐Binding Site
Chain Initiation
Initiation Factor 2 Is a GTPase
The 70S Initiation Complex
BrainBox 6.1 John Shine
Example 6.1 The Irritating Formyl Methionine
Elongation of the Protein Chain in Bacteria
IN DEPTH 6.2 PEPTIDYL TRANSFERASE IS A RIBOZYME
The Polyribosome
Termination of Protein Synthesis
Medical Relevance 6.1 A Premature STOP
The Ribosome Is Recycled
EUKARYOTIC PROTEIN SYNTHESIS IS A LITTLE MORE COMPLEX
BrainBox 6.2 Venkatraman Ramakrishnan, Thomas Steitz, and Ada Yonath
Example 6.2 The Diptheria Bacterium Inhibits Protein Synthesis
ANTIBIOTICS AND PROTEIN SYNTHESIS
PROTEIN DESTRUCTION
IN DEPTH 6.3 PROTEOMICS
SUMMARY
FURTHER READING
REVIEW QUESTIONS
THOUGHT QUESTION
7 PROTEIN STRUCTURE
NAMING PROTEINS
POLYMERS OF AMINO ACIDS
The Amino Acid Building Blocks
IN DEPTH 7.1 HYDROPATHY PLOTTING – THE PDGF RECEPTOR
The Unique Properties of Each Amino Acid
Example 7.1 The Salt Bridges in ROMK Hold the Channel Open
Medical Relevance 7.1 Adding a Hydrophobic Group to Ras
OTHER AMINO ACIDS ARE FOUND IN NATURE
THE THREE‐DIMENSIONAL STRUCTURES OF PROTEINS
Hydrogen Bonds
Electrostatic Interactions
Van der Waals Forces
Hydrophobic Interactions
Disulfide Bonds
LEVELS OF COMPLEXITY
The Primary Structure
The Secondary Structure
IN DEPTH 7.2 CHIRALITY AND AMINO ACIDS
Tertiary Structure: Domains and Motifs
BrainBox 7.1 Christine Orengo and Janet Thornton
Quaternary Structure: Assemblies of Protein Subunits
PROSTHETIC GROUPS
THE PRIMARY STRUCTURE CONTAINS ALL THE INFORMATION NECESSARY TO SPECIFY HIGHER‐LEVEL STRUCTURES
Medical Relevance 7.2 Protein Folding Gone Awry: Congenital Hypothyroidism
Medical Relevance 7.3 Protein Folding Gone Awry: Alzheimer's Disease
PROTEIN–PROTEIN INTERACTIONS UNDERLIE ALL OF CELL BIOLOGY
IN DEPTH 7.3 LEVINTHAL'S PARADOX
SUMMARY
FURTHER READING
REVIEW QUESTIONS
THOUGHT QUESTION
8 RECOMBINANT DNA TECHNOLOGYAND GENETIC ENGINEERING
DNA CLONING
CREATING THE CLONE
Introduction of Foreign DNA Molecules into Bacteria
Joining Foreign DNAs to a Cloning Vector
Medical Relevance 8.1 mRNA Therapeutics
Introduction of Recombinant Plasmids into Bacteria
Genomic DNA Clones
Example 8.1 Cloning a Receptor Protein cDNA
USES OF DNA CLONES
Southern Blotting
In‐Situ Hybridization
Northern Blotting
Production of Mammalian Proteins in Bacteria and Eukaryotic Cells
Polymerase Chain Reaction
DNA Sequencing
Next‐Generation Sequencing
Example 8.2 Steps Toward Clinical Gene Therapy
“OMICS”
Transcriptomics
Microarrays
RNA‐Seq
Medical Relevance 8.2 Microarrays and Cancer Classification
ChIP‐Seq and Epigenomics
IN DEPTH 8.1 GENETICALLY MODIFIED (GM) PLANTS – CAN THEY HELP FIGHT MALNUTRITION?
Other “Omics”
IDENTIFYING THE GENE RESPONSIBLE FOR A DISEASE
REVERSE GENETICS
TRANSGENIC AND KNOCKOUT MICE
RNA INTERFERENCE (RNAi)
BrainBox 8.1 Andrew Fire and Craig Mello
CRISPR/CAS9
BrainBox 8.2 Emmanuelle Charpentier and Jennifer Doudna
ETHICS OF DNA TESTING FOR INHERITED DISEASE
SUMMARY
FURTHER READING
REVIEW QUESTIONS
THOUGHT QUESTION
SECTION 3. CELL COMMUNICATION
9 CARRIERS, CHANNELS, AND VOLTAGES
CARRIERS
Medical Relevance 9.1 Cytochrome c – Vital but Deadly
The Glucose Carrier
Example 9.1 The Glucose Carrier Is Essential
The Sodium/Calcium Exchanger
The Sodium/Potassium ATPase
The Calcium ATPase
Medical Relevance 9.2 Poisoned Hearts Are Stronger
THE POTASSIUM GRADIENT AND THE RESTING VOLTAGE
Potassium Channels Make the Plasma Membrane Permeable to Potassium Ions
IN DEPTH 9.1 MEASURING THE MEMBRANE VOLTAGE
Concentration Gradients and Electrical Voltage Can Balance
IN DEPTH 9.2 THE NERNST EQUATION
THE ACTION POTENTIAL
The Pain Receptor Neuron
Example 9.2 Peppers and Pain
The Voltage‐Gated Sodium Channel
The Sodium Action Potential
Example 9.3 Chewing off the Inactivation Plug
The Strength of a Signal Is Coded by Action Potential Frequency
Example 9.4 Local Anesthetic, Overall Wellbeing
Myelination and Rapid Action Potential Transmission
IN DEPTH 9.3 VOLTAGE‐GATED POTASSIUM CHANNELS
SUMMARY
FURTHER READING
REVIEW QUESTIONS
THOUGHT QUESTION
10 SIGNALING THROUGH IONS
CALCIUM AS A SIGNALING ION
Calcium Can Enter Cells from the Extracellular Medium
Calcium Can Be Released from Organelles
Processes Activated by Cytosolic Calcium Are Extremely Diverse
Example 10.1 Visualizing Calcium Signals
Return of Calcium to Resting Levels
PROPAGATING THE SIGNAL
Transmitters Are Released at Synapses
Example 10.2 A Toxic Glutamate Analogue
Ligand‐Gated Ion Channels Respond to Transmitters
RAPID COMMUNICATION: FROM NEURONS TO THEIR TARGETS
Inhibitory Transmission
IN DEPTH 10.1 ION CHANNEL STRUCTURE: VARIATIONS ON A THEME
Signaling at the Neuromuscular Junction
SUMMARY
REVIEW QUESTIONS
THOUGHT QUESTION
11 SIGNALING THROUGH ENZYMES
G PROTEIN‐COUPLED RECEPTORS AND SECOND MESSENGERS
G Protein‐Coupled Receptors Are an Abundant Class of Cell Surface Receptors
Inositol Trisphosphate Controls Secretion in the Exocrine Pancreas
Cyclic Adenosine Monophosphate Helps Us Smell
IN DEPTH 11.1 HETEROTRIMERIC G PROTEINS: A FORTUITOUS DISCOVERY
RECEPTOR TYROSINE KINASES AND THE MAP KINASE CASCADE
Medical Relevance 11.1 Blocking Growth Factor Receptors
Growth Factors Can Trigger a Calcium Signal
Akt and the Glucose Carrier: How Insulin Works
CYTOKINE RECEPTORS
SIGNALING THROUGH PROTEOLYSIS
Wnt Proteins Signal Through Receptors that Prevent Proteolysis of Beta Catenin
Low Oxygen Levels Are Sensed by Preventing Proteolysis of Hypoxia‐Inducing Factor
INTRACELLULAR RECEPTORS
Guanylate Cyclase Is a Receptor for Nitric Oxide
Many Steroid Hormone Receptors Are Transcription Factors
CROSSTALK – SIGNALING PATHWAYS OR SIGNALING WEBS?
BrainBox 11.1 Stephen Mayo
SIGNALING IN THE CONTROL OF MUSCLE BLOOD SUPPLY
The Blood Supply Is Under Local Control
Example 11.1 Nitroglycerine Relieves Angina
Example 11.2 Viagra
The Blood Supply Is Under Nervous System Control
The Blood Supply Is Under Hormonal Control
New Blood Vessels in Growing Muscle
IN DEPTH 11.2 FIGHT OR FLIGHT: SHOULD I STAY OR SHOULD I GO?
Answer to Thought Question:
SUMMARY
FURTHER READING
REVIEW QUESTIONS
THOUGHT QUESTION
SECTION 4. THE MECHANICS OF THE CELL
12 INTRACELLULAR TRAFFICKING
PRINCIPLES OF PROTEIN TRANSPORT
Proteins Enter Organelles in Different Ways
Vesicles Shuttle Proteins Around the Cell Through Fission and Fusion
Example 12.1 SNARES, Food Poisoning, and Face‐Lifts
The Destination of a Protein Is Determined by Sorting Signals
Example 12.2 Holding Calcium Ions in the Endoplasmic Reticulum
GTPases Are Master Regulators of Traffic
TRAFFICKING TO THE ENDOPLASMIC RETICULUM AND PLASMA MEMBRANE
Synthesis on the Rough Endoplasmic Reticulum
Glycosylation: The Endoplasmic Reticulum and Golgi System
Example 12.3 Cyclists and Glycosylation
Coatomer‐Coated Vesicles
Trans Golgi Network and Protein Secretion
TRAFFICKING TO THE LYSOSOME
Endocytosis Is a Gateway into the Cell
IN DEPTH 12.1 SNEAKING INTO THE CELL
Clathrin‐Coated Vesicles
Delivery of Enzymes to Lysosomes
Medical Relevance 12.1 Failure of the Lysosome‐Targeting Signal
Lysosomes Degrade Proteins from both Outside and Inside of the Cell: Autophagy
TRAFFICKING TO AND FROM THE NUCLEUS
The Nuclear Pore Complex
Gated Transport Through the Nuclear Pore
GTPases in Nuclear Transport
TRAFFICKING TO OTHER ORGANELLES. Transport to Mitochondria
Medical Relevance 12.2 Blocking Calcineurin – How Immunosuppressants Work
Transport to Peroxisomes
SUMMARY
Medical Relevance 12.3 How Protein Mistargeting Can Give You Kidney Stones
FURTHER READING
REVIEW QUESTIONS
THOUGHT QUESTION
13 CELLULAR SCAFFOLDING
MICROTUBULES
Example 13.1 Microtubule Dynamic Instability Helps Them “Search and Capture” Chromosomes in Mitosis
FUNCTIONS OF MICROTUBULES
Intracellular Transport and Cellular Architecture
Cell Movement by Cilia and Flagella
MICROFILAMENTS
Medical Relevance 13.1 Some Bacteria Highjack the Cytoskeleton for Their Own Purposes
FUNCTIONS OF MICROFILAMENTS
Muscle Contraction
Microfilament‐Based Cell Migration
INTERMEDIATE FILAMENTS
IN DEPTH 13.1 CYTOSKELETAL PROTEINS IN PROKARYOTES
FUNCTIONS OF INTERMEDIATE FILAMENTS. Anchoring Cell Junctions
IN DEPTH 13.2 DYSTROPHIN: A STRONG MULTILINKER
The Nuclear Lamina
Medical Relevance 13.2 Protected by the Dead
SUMMARY
FURTHER READING
REVIEW QUESTIONS
THOUGHT QUESTION
14 CONTROLLING CELL NUMBER
IN DEPTH 14.1 STEM CELLS
M‐PHASE
Mitosis
Example 14.1 Taxol Stops Mitosis
Cytokinesis
Example 14.2 Counting Chromosomes
CONTROL OF THE CELL CYCLE. The Cell Cycle Is Driven by Kinase Activities
Checkpoints Tell the Cell Cycle When to Stop and When to Go
Medical Relevance 14.1 Retinoblastoma
The Mitotic Checkpoint Determines When the Cell Cycle Ends
Cell Cycle Control and Cancer
MEIOSIS AND FERTILIZATION
Meiosis
Medical Relevance 14.2 Down's Syndrome
Crossing Over and Linkage
CELL DEATH
Example 14.3 Sunburn, Cell Death, and Skin Cancer
Cell Stress Activates the Intrinsic Apoptotic Pathway
Communication with the External Environment Can Activate the Extrinsic Apoptotic Pathway
Example 14.4 Neurotrophin Trafficking
Default Death: Apoptosis as a Result of Absence of Growth Factors
SUMMARY
FURTHER READING
REVIEW QUESTIONS
THOUGHT QUESTION
SECTION 5. CASE STUDY
15 CASE STUDY: CYSTIC FIBROSIS
CYSTIC FIBROSIS IS A SEVERE GENETIC DISEASE
THE FUNDAMENTAL LESION IN CYSTIC FIBROSIS LIES IN CHLORIDE TRANSPORT
CLONING THE CFTR GENE
THE CFTR GENE CODES FOR A CHLORIDE ION CHANNEL
Brain Box 15.1 Dorothy Hansine Anderson, Lap‐Chee Tsui, and Michael Welsh
IN DEPTH 15.1 LIPID BILAYER VOLTAGE CLAMP
REPLACING OR REPAIRING THE GENE
Medical Relevance 15.1 Gene Therapy for Leber Congenital Amaurosis
TAILORING TREATMENT TO THE PATIENT'S LESION
NEW TREATMENTS FOR CF
DIAGNOSTIC TESTS FOR CF
Prenatal implantation diagnosis for CF
CONCLUSION
SUMMARY
FURTHER READING
REVIEW QUESTIONS
THOUGHT QUESTIONS
ANSWERS TO REVIEW QUESTIONS
GLOSSARYGlossary
INDEX
WILEY END USER LICENSE AGREEMENT
