Cell Biology

Stephen Bolsover is Professor Emeritus of Cell Physiology at University College London (UCL). His research focussed on the role of calcium as an intracellular messenger. Andrea Townsend-Nicholson is Professor of Biochemistry & Molecular Biology at UCL. She is particularly interested in integrating high performance computing and experimental methodologies for the study of G protein-coupled receptors. She served as the Head of Teaching for Molecular Biosciences at UCL from 2010-2019. Greg FitzHarris was previously a student and then lecturer at UCL, and is now Professor and Head of the Department of Pathology and Cell Biology at Université de Montréal. Elizabeth Shephard is a Professorial Research Associate at UCL. She has a particular interest in rare genetic disorders and is a scientific advisor for the patient advocacy group, MEBO Research. She has served terms as Vice-Dean Education, Faculty Life Sciences, UCL. Jeremy Hyams was Professor of Cell Biology at UCL. He left in 2003 to become head of the Institute of Molecular Biosciences at Massey University, New Zealand. He retired in 2008. Sandip Patel is Professor of Cell Signalling and Deputy Head of the Department of Cell and Developmental Biology at UCL. He has been teaching cell biology to variety of students for more years than he cares to remember but finds time to run a research lab.

• Preface, xiAcknowledgments, xiiiAbout the companion website, xvSection 1: The Structure of the Cell, 11 A Look at Cells and Tissues, 3Only Two Types of Cell, 3Cell Division, 4Viruses, 4Origin of Eukaryotic Cells, 6Cell Specialization in Animals, 8Stem Cells and Tissue Replacement, 10The Cell Wall, 11Microscopes Reveal Cell Structure, 11The Modern Light Microscope, 11The Transmission Electron Microscope, 12The Scanning Electron Microscope, 14Fluorescence Microscopy, 14Increasing the Resolution of Fluorescence Microscopes, 15Fluorescent Proteins, 152 Membranes and Organelles, 21Basic Properties of Cell Membranes, 21Organelles Bounded by Double-Membrane Envelopes, 22The Nucleus, 22Mitochondria, 24Organelles Bounded by Single Membranes, 24Peroxisomes, 25Endoplasmic Reticulum, 25Golgi Apparatus, 25Lysosomes, 25The Connected Cell, 26Organelle Junctions, 26Cell Junctions, 26Section 2: The Molecular Biology Of The Cell, 333 DNA Structure And The Genetic Code, 35The Structure of DNA, 35The DNA Molecule Is a Double Helix, 37Hydrogen Bonds Form Between Base Pairs, 37DNA Strands Are Antiparallel, 37The Two DNA Strands Are Complementary, 39DNA as the Genetic Material, 39Packaging of DNA Molecules into Chromosomes, 39Eukaryotic Chromosomes and Chromatin Structure, 39Prokaryotic Chromosomes, 40Plasmids, 41Viruses, 42The Genetic Code, 42Amino Acids and Proteins, 42Reading the Genetic Code, 42Amino Acid Names Are Abbreviated, 44The Code Is Degenerate but Unambiguous, 44Start and Stop Codons and the Reading Frame, 45The Code Is Nearly Universal, 45Missense Mutations, 464 DNA As A Data Storage Medium, 51DNA Replication, 51The DNA Replication Fork, 51Proteins Open up the DNA Double Helix During Replication, 51DnaA Protein, 52DnaB and DnaC Proteins, 52Single-Stranded DNA-Binding Proteins, 52Biochemistry of DNA Replication, 52DNA Synthesis Requires an RNA Primer, 55RNA Primers Are Removed, 55The Self-Correcting DNA Polymerase, 55Mismatch Repair Backs Up the Proofreading Mechanism, 55DNA Repair after Replication, 56Spontaneous and Chemically Induced Base Changes, 56Repair Processes, 57Gene Structure and Organization in Eukaryotes, 59Introns and Exons – Additional Complexity in Eukaryotic Genes, 59The Major Classes of Eukaryotic DNA, 60Gene Nomenclature, 615 Transcription and the Control of Gene Expression, 67Structure of RNA, 67RNA Polymerase, 67Gene Notation, 68Bacterial RNA Synthesis, 69Control of Bacterial Gene Expression, 71Lac, an Inducible Operon, 71Trp, a Repressible Operon, 74Eukaryotic RNA Synthesis, 75Messenger RNA Processing in Eukaryotes, 76Control of Eukaryotic Gene Expression, 77Glucocorticoids Cross the Plasma Membrane to Activate Transcription, 79Noncoding RNAs and the Control of Eukaryotic Gene Expression, 80Micro RNAs, 80Long Noncoding RNAs, 81Circular RNAs, 816 Manufacturing Protein, 85Attachment of an Amino Acid to Its tRNA, 85Transfer RNA, the Anticodon, and Wobble, 85The Ribosome, 89Bacterial Protein Synthesis, 89Ribosome-Binding Site, 89Chain Initiation, 90Initiation Factor 2 Is a GTPase, 90The 70S Initiation Complex, 91Elongation of the Protein Chain in Bacteria, 92The Polyribosome, 94Termination of Protein Synthesis, 94The Ribosome Is Recycled, 95Eukaryotic Protein Synthesis Is a Little More Complex, 95Antibiotics and Protein Synthesis, 97Protein Destruction, 987 Protein Structure, 103Naming Proteins, 103Polymers of Amino Acids, 104The Amino Acid Building Blocks, 104The Unique Properties of Each Amino Acid, 107Other Amino Acids Are Found in Nature, 109The Three-Dimensional Structures of Proteins, 109Hydrogen Bonds, 109Electrostatic Interactions, 109Van der Waals Forces, 109Hydrophobic Interactions, 109Disulfide Bonds, 109Levels of Complexity, 110The Primary Structure, 110The Secondary Structure, 111Tertiary Structure: Domains and Motifs, 114Quaternary Structure: Assemblies of Protein Subunits, 118Prosthetic Groups, 118The Primary Structure Contains all the Information Necessary to Specify Higher-Level Structures, 119Protein–Protein Interactions Underlie all of Cell Biology, 1198 Recombinant DNA Technology and Genetic Engineering, 123DNA Cloning, 123Creating the Clone, 124Introduction of Foreign DNA Molecules into Bacteria, 124Genomic DNA Clones, 126Uses of DNA Clones, 128Southern Blotting, 129In-Situ Hybridization, 130Northern Blotting, 130Production of Mammalian Proteins in Bacteria and Eukaryotic Cells, 130Polymerase Chain Reaction, 132DNA Sequencing, 133“Omics”, 135Transcriptomics, 135Microarrays, 135RNA-Seq, 136ChIP-Seq and Epigenomics, 136Other “Omics”, 137Identifying the Gene Responsible for a Disease, 137Reverse Genetics, 137Transgenic and Knockout Mice, 137RNA Interference (RNAi), 139CRISPR/Cas9, 139Ethics of DNA Testing for Inherited Disease, 140Section 3: Cell Communication, 1459 Carriers, Channels, And Voltages, 147Carriers, 147The Glucose Carrier, 149The Sodium/Calcium Exchanger, 150The Sodium/Potassium ATPase, 150The Calcium ATPase, 151The Potassium Gradient and the Resting Voltage, 152Potassium Channels Make the Plasma Membrane Permeable to Potassium Ions, 152Concentration Gradients and Electrical Voltage Can Balance, 154The Action Potential, 156The Pain Receptor Neuron, 156The Voltage-Gated Sodium Channel, 158The Sodium Action Potential, 158The Strength of a Signal Is Coded by Action Potential Frequency, 159Myelination and Rapid Action Potential Transmission, 16110 Signalling Through Ions, 165Calcium as a Signaling Ion, 165Calcium Can Enter Cells from the Extracellular Medium, 165Calcium Can Be Released from Organelles, 166Processes Activated by Cytosolic Calcium Are Extremely Diverse, 167Return of Calcium to Resting Levels, 169Propagating the Signal, 170Transmitters Are Released at Synapses, 170Ligand-Gated Ion Channels Respond toTransmitters, 170Rapid Communication: From Neurons to Their Targets, 171Inhibitory Transmission, 172Signaling at the Neuromuscular Junction, 17511 Signalling Through Enzymes, 179G Protein-Coupled Receptors and Second Messengers, 179G Protein-Coupled Receptors Are an Abundant Class of Cell Surface Receptors, 179Inositol Trisphosphate Controls Secretion in the Exocrine Pancreas, 179Cyclic Adenosine Monophosphate Helps Us Smell, 181Receptor Tyrosine Kinases and the Map Kinase Cascade, 183Growth Factors Can Trigger a Calcium Signal, 185Akt and the Glucose Carrier: How Insulin Works, 185Cytokine Receptors, 187Signaling Through Proteolysis, 188Wnt Proteins Signal Through Receptors that Prevent Proteolysis of Beta Catenin, 188Low Oxygen Levels Are Sensed by Preventing Proteolysis of Hypoxia-Inducing Factor, 189Intracellular Receptors, 190Guanylate Cyclase Is a Receptor for Nitric Oxide, 190Many Steroid Hormone Receptors Are Transcription Factors, 190Crosstalk – Signaling Pathways or Signaling Webs?, 190Signaling in the Control of Muscle Blood Supply, 192The Blood Supply Is Under Local Control, 193The Blood Supply Is Under Nervous System Control, 193The Blood Supply Is Under Hormonal Control, 194New Blood Vessels in Growing Muscle, 194Section 4: The Mechanics Of The Cell, 19912 Intracellular Trafficking, 201Principles of Protein Transport, 201Proteins Enter Organelles in Different Ways, 201Vesicles Shuttle Proteins Around the Cell Through Fission and Fusion, 202The Destination of a Protein Is Determined by Sorting Signals, 204GTPases Are Master Regulators of Traffic, 205Trafficking to the Endoplasmic Reticulum and Plasma Membrane, 205Synthesis on the Rough Endoplasmic Reticulum, 205Glycosylation: The Endoplasmic Reticulum and Golgi System, 206Coatomer-Coated Vesicles, 207Trans Golgi Network and Protein Secretion, 208Trafficking to the Lysosome, 209Endocytosis Is a Gateway into the Cell, 209Clathrin-Coated Vesicles, 209Delivery of Enzymes to Lysosomes, 209Lysosomes Degrade Proteins from both Outside and Inside of the Cell: Autophagy, 210Trafficking to and from the Nucleus, 210The Nuclear Pore Complex, 211Gated Transport Through the Nuclear Pore, 212GTPases in Nuclear Transport, 212Trafficking to Other Organelles, 212Transport to Mitochondria, 212Transport to Peroxisomes, 21513 CELLULAR SCAFFOLDING, 219Microtubules, 219Functions of Microtubules, 222Intracellular Transport and Cellular Architecture, 222Cell Movement by Cilia and Flagella, 223Microfilaments, 225Functions of Microfilaments, 226Muscle Contraction, 226Microfilament-Based Cell Migration, 227Intermediate Filaments, 228Functions of Intermediate Filaments, 229Anchoring Cell Junctions, 229The Nuclear Lamina, 23014 Controlling Cell Number, 233M-phase, 235Mitosis, 235Cytokinesis, 236Control of the Cell Cycle, 238The Cell Cycle Is Driven by Kinase Activities, 238Checkpoints Tell the Cell Cycle When to Stop and When to Go, 239The Mitotic Checkpoint Determines When the Cell Cycle Ends, 241Cell Cycle Control and Cancer, 241Meiosis and Fertilization, 242Meiosis, 242Crossing Over and Linkage, 245Cell Death, 246Cell Stress Activates the Intrinsic Apoptotic Pathway, 246Communication with the External Environment Can Activate the Extrinsic Apoptotic Pathway, 247Default Death: Apoptosis as a Result of Absence of Growth Factors, 248Section 5 Case Study, 25315 Case Study: Cystic Fibrosis, 255Cystic Fibrosis Is a Severe Genetic Disease, 255The Fundamental Lesion in Cystic Fibrosis Lies in Chloride Transport, 256Cloning the CFTR Gene, 256The CFTR Gene Codes for a Chloride Ion Channel, 257Replacing or Repairing the Gene, 259Tailoring Treatment to the Patient’s Lesion, 260New Treatments for CF, 261Diagnostic Tests for CF, 261Prenatal implantation diagnosis for CF, 262Conclusion, 262Answers to Review Questions, 265Glossary, 273Index, 307