Medical Cell Biology THIRD EDITION Companion Web Site: http://www.books.elsevier.com/companions/9780123704580 Medical Cell Biology, Third Edition, by Steven R Goodman Resources for Professors: • All figures from the book available as PowerPoint slides • Links to web sites carefully chosen to supplement the content of the textbook • Contact the editor with questions and/or suggestions To adopt this book for course use, visit http://textbooks.elsevier.com Medical Cell Biology THIRD EDITION Edited by Steven R Goodman, PhD C.L and Amelia A Lundell Professor of Life Sciences The University of Texas at Dallas Richardson, Texas Adjunct Professor of Cell Biology University of Texas Southwestern Medical Center Dallas, Texas AMSTERDAM • BOSTON • HEIDELBERG • LONDON NEW YORK • OXFORD • PARIS • SAN DIEGO SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Academic Press is an imprint of Elsevier Academic Press is an imprint of Elsevier 30 Corporate Drive, Suite 400, Burlington, MA 01803, USA 525 B Street, Suite 1900, San Diego, California 92101-4495, USA 84 Theobald’s Road, London, WC1X 8RR, UK This book is printed on acid-free paper Copyright © 2008, Elsevier Inc All rights reserved Notice No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher Permissions may be sought directly from Elsevier’s Science & Technology Rights Department in Oxford, UK: phone: (+44) 1865 843830, fax: (+44) 1865 853333, E-mail: permissions@elsevier com You may also complete your request online via the Elsevier homepage (http://elsevier.com), by selecting “Support and Contact” then “Copyright and Permissions” and then “Obtaining Permissions.” The Publisher Library of Congress Cataloging-in-Publication Data 2007926489 British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library ISBN 978-0-12-370458-0 For information on all Elsevier Academic Press publications, visit our Web site at www.books.elsevier.com Working together to grow libraries in developing countries www.elsevier.com | www.bookaid.org | www.sabre.org Printed in China 07 08 09 10 11 12 I dedicate this third edition of Medical Cell Biology to my family wife, Cindy; sister, Sue; and children, Laela, Gena, Jessie, David, Christie, and Laurie my friends Obe, Ian, Charlie, Lynn, Santosh, Sandi, Rocky, Steve L., Stephen, Da Hsuan, and many others my scientific heroes Britton Chance, Aaron Ciechanover, Russell Hulse, and Alan MacDiarmid and my students, past and current This page intentionally left blank Contents Contributors Preface Chapter Tools of the Cell Biologist Microscopy: One of the Earliest Tools of the Cell Biologist Fluorescence Microscopy Immunolabeling Genetic Tagging Electron Microscopy Transmission Electron Microscopy Scanning Electron Microscopy Atomic-Force Microscopy More Tools of Cell Biology Cell Culture Flow Cytometry Subcellular Fractionation The Techniques of Proteomics and Genomics Are Discussed in Later Chapters Summary Chapter Cell Membranes Membrane Lipids The Lipid Composition of Human and Animal Biological Membranes Includes Phospholipids, Cholesterol, and Glycolipids Membrane Lipids Undergo Continuous Turnover Membrane Lipids Are Constantly in Motion Membrane Protein–Lipid Interactions Are Important Mediators of Function Integral and Peripheral Membrane Proteins Differ in Structure and Function Membrane Protein Organization Optical Technologies Such as Microscopy and Flow Cytometry Have Revolutionized the Study of Membranes Important Changes in Membrane Phospholipids Occur in Sickle Cell Disease The Cell Membrane Is a Selective Permeability Barrier That Maintains Distinct Internal and External Cellular Environments xi xiii 14 15 15 18 18 19 19 22 23 25 25 27 29 29 30 33 36 36 38 38 41 43 Water Movement across Membranes Is Based on Osmosis Donnan Effect and Its Relation to Water Flow Facilitated Transport Active Transport Secondary Active Transport Ion Channels and Membrane Potentials The Membrane Potential Is Caused by a Difference in Electric Charge on the Two Sides of the Plasma Membrane Action Potentials Are Propagated at the Axon Hillock Summary Chapter Cytoskeleton Microfilaments Actin-Based Cytoskeletal Structures Were First Described in Muscle Tissue Skeletal Muscle Is Formed from Bundles of Muscle Fibers The Functional Unit of Skeletal Muscle Is the Sarcomere Thin Filaments Are Built from the Proteins Actin, Tropomyosin, Troponin, and Tropomodulin Thick Filaments Are Composed of the Protein Myosin Accessory Proteins Are Responsible for Maintenance of Myofibril Architecture Muscle Contraction Involves the Sliding of the Thick and Thin Filaments Relative to Each Other in the Sarcomere Adenosine Triphosphate Hydrolysis Is Necessary for Cross-Bridge Interactions with Thin Filaments Calcium Regulation of Skeletal Muscle Contraction Is Mediated by Troponin and Tropomyosin Intracellular Calcium in Skeletal Muscle Is Regulated by a Specialized Membrane Compartment, the Sarcoplasmic Reticulum Three Types of Muscle Tissue Exist The Contractile Apparatus of Smooth Muscle Contains Actin and Myosin 44 46 47 48 48 49 52 54 56 59 59 59 60 60 60 64 64 66 67 68 69 70 73 vii viii Contents Smooth-Muscle Contraction Occurs via Myosin-Based Calcium Ion Regulatory Mechanisms Smooth-Muscle Contraction Is Influenced at Multiple Levels Actin-Myosin Contractile Structures Are Found in Nonmuscle Cells Members of the Myosin Supergene Family Are Responsible for Movement of Vesicles and Other Cargo Along Actin Tracks in the Cytoplasm Bundles of F-Actin Form a Structural Support for the Microvilli of Epithelial Cells The Gel-Sol State of the Cortical Cytoplasm Is Controlled by the Dynamic Status of Actin Cell Motility Requires Coordinated Changes in Actin Dynamics Inhibitors of Actin-Based Function Actin-Binding Proteins The ERM Family Mediates End-on Association of Actin with the Cytoplasmic Surface of the Plasma Membrane Spectrin Membrane Skeleton The Structure and Function of the Erythrocyte Spectrin Membrane Skeleton Are Understood in Exquisite Detail Spectrin Is a Ubiquitous Component of Nonerythroid Cells Spectrins I and II, α-Actinin, and Dystrophin Form the Spectrin Supergene Family Regulation of Actin Dynamics Intermediate Filaments A Heterogeneous Group of Proteins Form Intermediate Filaments in Various Cells How Can Such a Heterogeneous Group of Proteins All Form Intermediate Filaments? Microtubules Microtubules Are Polymers Composed of Tubulin Microtubules Undergo Rapid Assembly and Disassembly By Capping the Minus Ends of Microtubules, the Centrosome Acts as a Microtubule-Organizing Center The Behavior of Cytoplasmic Microtubules Can Be Regulated Microtubules Are Involved in Intracellular Vesicle and Organelle Transport Cilia and Flagella Are Specialized Organelles Composed of Microtubules Axonemal Microtubules Are Stable Microtubule Sliding Results in Axonemal Motility 74 Microtubules and Motor Proteins Are Responsible for the Function of the Mitotic Spindle Summary 98 100 75 75 77 78 78 79 81 81 81 82 82 85 86 88 89 89 90 91 91 91 92 94 95 95 97 97 Chapter Organelle Structure and Function The Nucleus Endoplasmic Reticulum Smooth Endoplasmic Reticulum Rough Endoplasmic Reticulum Leaving the Endoplasmic Reticulum: A Paradigm for Vesicular Traffic Overview of Vesicle Budding, Targeting, and Fusion Endoplasmic Reticulum to Golgi Vesicle Transport and COPII-Coated Vesicles The Golgi Apparatus Glycosylation and Covalent Modification of Proteins in the Golgi Apparatus Retrograde Transport through the Golgi Complex Anterograde Transport through the Golgi Complex Leaving the Golgi Complex Constitutive and Regulated Secretion Lysosomal Enzymes Are Targeted via a Mannose 6-Phosphate Signal Endocytosis, Endosomes, and Lysosomes Clathrin-Dependent Endocytosis Receptor-Mediated Endocytosis of LowDensity Lipoprotein and Transferrin Multivesicular Endosomes Lysosomes The Ubiquitin-Proteasome System Is Responsible for Nonlysosomal Protein Degradation Mitochondria ATP Production by Oxidative Phosphorylation Mitochondrial Genetic System Defects in Mitochondrial Function Can Cause Disease Mitochondria Import Most of Their Proteins from the Cytosol Peroxisomes Summary Chapter Regulation of Gene Expression Cell Nucleus Nucleus Structure Nuclear Function DNA Replication and Repair Are Critical Nuclear Functions Replication of DNA Occurs during the Synthetic (S) Phase of the Cell Cycle DNA Repair Is a Critical Process of Cell Survival 101 103 104 104 107 118 118 121 121 122 123 125 125 125 126 128 128 129 131 132 132 134 134 140 140 143 145 147 149 149 149 155 156 156 159 Contents Regulation of Gene Expression Genomics and Proteomics Restriction Nucleases: Enzymes That Cleave DNA at Specific Nucleotide Sequences Gene Cloning Can Produce Large Quantities of Any DNA Sequence The Primary Structure of a Gene Can Be Rapidly Determined by DNA Sequencing Specific Regions of the Genome Can Be Amplified with the Polymerase Chain Reaction Bioinformatics: Genomics and Proteomics Offer Potential for Personalized Medicine Transgenic Mice Offer Unique Models of Genetic Diseases Gene Expression: The Transfer of Information from DNA to Protein Genetic Therapy There Are Many Obstacles to the Development of Effective Gene Therapies Many Strategies Are Available for Gene-Based Therapies Summary Cell Adhesion and the Extracellular Matrix Cell Adhesion Most Cell Adhesion Molecules Belong to One of Four Gene Families Cadherins Are Calcium-Dependent Cell-Cell Adhesion Molecules The Immunoglobulin Family Contains Many Important Cell Adhesion Molecules Selectins Are Carbohydrate-Binding Adhesion Receptors Integrins Are Dimeric Receptors for Cell-Cell and Cell-Matrix Adhesion Intercellular Junctions Tight Junctions Regulate Paracellular Permeability and Cell Polarity Adherens Junctions Are Important for Cell-Cell Adhesion Desmosomes Maintain Tissue Integrity Gap Junctions Are Channels for Cell-Cell Communication Hemidesmosomes Maintain Cell-Matrix Adhesion Focal Contacts Are Adhesions Formed with the Substratum by Cultured Cells Cell Adhesion Has Many Important Roles in Tissue Function Junctions Maintain Epithelial Barrier Function and Polarity Leukocytes Must Adhere and Migrate to Combat Infection and Injury 165 165 165 167 167 168 170 172 174 189 189 189 190 Platelets Adhere to Form Blood Clots Embryonic Development Involves Many Adhesion-Dependent Events Cell Adhesion Receptors Transmit Signals That Regulate Cell Behavior Cell Growth and Cell Survival Are Adhesion Dependent Cell Adhesion Regulates Cell Differentiation Extracellular Matrix Collagen Is the Most Abundant Protein in the Extracellular Matrix Glycosaminoglycans and Proteoglycans Absorb Water and Resist Compression Elastin and Fibrillin Provide Tissue Elasticity Fibronectin Is Important for Cell Adhesion Laminin Is a Key Component of Basement Membranes Basement Membranes Are Thin Matrix Layers Specialized for Cell Attachment Fibrin Forms the Matrix of Blood Clots and Assembles Rapidly When Needed von Willebrand Factor in Normal and Abnormal Blood Clotting Summary ix 210 212 213 214 215 215 216 218 220 220 220 221 222 223 224 Chapter 191 192 192 192 193 194 195 195 196 198 200 203 203 206 207 207 209 Chapter Intercellular Signaling General Modes of Intercellular Signaling Intercellular Signaling Molecules Act as Ligands Cells Exhibit Differential Responses to Signaling Molecules Intercellular Signaling Molecules Act via Multiple Mechanisms Hormones Lipophilic Hormones Activate Cytosolic Receptors Receptors for Lipophilic Hormones Are Members of the Nuclear Receptor Superfamily Peptide Hormones Activate Membrane-Bound Receptors The Hypothalamic-Pituitary Axis Growth Factors Nerve Growth Factor Growth Factor Families Growth Factor Synthesis and Release Growth Factor Receptors Are Enzyme-Linked Receptors Growth Factors Are Paracrine and Autocrine Signalers Some Growth Factors Can Act over Long Distances Some Growth Factors Interact with Extracellular Matrix Components Histamine Histamine Receptor Subtypes 227 227 227 227 228 228 228 231 231 233 234 235 235 236 236 236 237 237 237 238 ... Are Dimeric Receptors for Cell- Cell and Cell- Matrix Adhesion Intercellular Junctions Tight Junctions Regulate Paracellular Permeability and Cell Polarity Adherens Junctions Are Important for Cell- Cell... Hypothalamic-Pituitary Axis Growth Factors Nerve Growth Factor Growth Factor Families Growth Factor Synthesis and Release Growth Factor Receptors Are Enzyme-Linked Receptors Growth Factors Are Paracrine and...Medical Cell Biology THIRD EDITION Companion Web Site: http://www.books.elsevier.com/companions/9780123704580 Medical Cell Biology, Third Edition, by Steven R Goodman Resources for Professors: •