JWCL151_fendpapers.qxd 9/14/09 11:09 AM Page 2 Nobel Prizes Awarded for Research in Cell and Molecular Biology Since 1958 Year Recipient* Prize Area ofResearch Pages in Text 2008 Francoise Barré-Sinoussi M & P** Discovery of HIV 23 Luc Montagnier Harald zur Hausen Role of HPV in cancer 654 Martin Chalfie Chemistry Discovery and development 267,720 Osamu Shimomura of GFP Roger Tsien 2007 Mario R.Capecchi M & P Development of techniques 760 Martin J.Evans for knockout mice Oliver Smithies 2006 Andrew Z.Fire M&P RNA Interference 449,762 Craig C.Mello Roger D.Kornberg Chemistry Transcription in eukaryotes 427,481 2004 Richard Axel M& P Olfactory receptors 622 Linda B.Buck Aaron Ciechanover Chemistry Ubiquitin and proteasomes 529 Avram Hershko Irwin Rose 2003 Peter Agre Chemistry Structure of membrane 146,148 Roderick MacKinnon channels 2002 Sydney Brenner M & P Introduction of C.elegans 17 John Sulston as a model organism H.Robert Horvitz Apoptosis in C.elegans 643 John B.Fenn Chemistry Electrospray ionization in MS 740 Koichi Tanaka MALDI in MS 740 Kurt Wüthrich NMR analysis of proteins 56 2001 Leland H.Hartwell M & P Control of the cell cycle 564,600 Tim Hunt Paul Nurse 2000 Arvid Carlsson M & P Synaptic transmission and 163 Paul Greengard signal transduction 605 Eric Kandel 1999 Günter Blobel M & P Protein trafficking 276 1998 Robert Furchgott M & P NO as intercellular 641 Louis Ignarro messenger Ferid Murad (cid:2) (cid:2) 1997 Jens C.Skou Chemistry Na /K -ATPase 153 Paul Boyer Mechanism of ATP synthesis 195 John Walker Stanley B.Prusiner M & P Protein nature of prions 64 1996 Rolf M.Zinkernagel M & P Recognition of virus-infected cells 709 Peter C.Doherty by the immune system 1995 Edward B.Lewis M & P Genetic control of EP12 Christiane Nüsslein-Volhard embryonic development Eric Wieschaus 1994 Alfred Gilman M & P Structure and function of 610 Martin Rodbell GTP-binding (G) proteins 1993 Kary Mullis Chemistry Polymerase chain reaction (PCR) 751 Michael Smith Site-directed mutagenesis (SDM) 760 Richard J.Roberts M & P Intervening sequences 438 Phillip A.Sharp JWCL151_fendpapers.qxd 9/14/09 11:09 AM Page 3 Year Recipient* Prize Area ofResearch Pages in Text 1992 Edmond Fischer M & P Alteration of enzyme activity by 112,614 Edwin Krebs phosphorylation/dephosphorylation 1991 Erwin Neher M & P Measurement of ion flux by 147 Bert Sakmann patch-clamp recording 1989 J.Michael Bishop M & P Cellular genes capable of causing 677 Harold Varmus malignant transformation Thomas R.Cech Chemistry Ability of RNA to catalyze reactions 469 Sidney Altman 1988 Johann Deisenhofer Chemistry Bacterial photosynthetic reaction 213 Robert Huber center Hartmut Michel 1987 Susumu Tonegawa M & P DNA rearrangements responsible 696 for antibody diversity 1986 Rita Levi-Montalcini M & P Factors that affect nerve outgrowth 372 Stanley Cohen 1985 Michael S.Brown M & P Regulation of cholesterol metabolism 312 Joseph L.Goldstein and endocytosis 1984 Georges Köhler M & P Monoclonal antibodies 763 Cesar Milstein Niels K.Jerne Antibody formation 687 Bruce Merrifield Chemistry Chemical synthesis of peptides 746 1983 Barbara McClintock M & P Mobile elements in the genome 402 1982 Aaron Klug Chemistry Structure of nucleic acid-protein 76 complexes 1980 Paul Berg Chemistry Recombinant DNA technology 748 Walter Gilbert DNA sequencing technology 753 Frederick Sanger Baruj Bennacerraf M & P Major histocompatibility complex 699 Jean Dausset George D.Snell 1978 Werner Arber M & P Restriction endonuclease technology 746 Daniel Nathans Hamilton O.Smith Peter Mitchell Chemistry Chemiosmotic mechanism of 181 oxidative phosphorylation 1976 D.Carleton Gajdusek M & P Prion-based diseases 64 1975 David Baltimore M & P Reverse transcriptase and tumor 676 Renato Dulbecco virus activity Howard M.Temin 1974 Albert Claude M & P Structure and function of internal 267 Christian de Duve components of cells George E.Palade 1972 Gerald Edelman M & P Immunoglobulin structure 693 Rodney R.Porter Christian B.Anfinsen Chemistry Relationship between primary and 62 tertiary structure of proteins 1971 Earl W.Sutherland M & P Mechanism of hormone 614 action and cyclic AMP 1970 Bernard Katz M & P Nerve impulse propagation 160 Ulf von Euler and transmission Luis F.Leloir Chemistry Role of sugar nucleotides in 280 carbohydrate synthesis 1969 Max Delbrück M & P Genetic structure of viruses 22,415 Alfred D.Hershey Salvador E.Luria JWCL151_fendpapers.qxd 9/14/09 11:09 AM Page 4 Year Recipient* Prize Area ofResearch Pages in Text 1968 H.Gobind Khorana M & P Genetic code 456 Marshall W.Nirenberg Robert W.Holley Transfer RNA structure 457 1966 Peyton Rous M & P Tumor viruses 676 1965 Francois Jacob M & P Bacterial operons and messenger 500,421 Andre M.Lwoff RNA Jacques L.Monod 1964 Dorothy C.Hodgkin Chemistry X-ray structure of complex biological molecules 740 1963 John C.Eccles M & P Ionic basis of nerve 159 Alan L.Hodgkin membrane potentials Andrew F.Huxley 1962 Francis H.C.Crick M & P Three-dimensional structure 386 James D.Watson of DNA Maurice H.F.Wilkins John C.Kendrew Chemistry Three-dimensional structure 56 Max F.Perutz of globular proteins 1961 Melvin Calvin Chemistry Biochemistry of CO assimilation 221 2 during photosynthesis 1960 F.MacFarlane Burnet M & P Clonal selection theory of 687 Peter B.Medawar antibody formation 1959 Arthur Kornberg M & P Synthesis of DNA and RNA 538,456 Severo Ochoa 1958 George W.Beadle M & P Gene expression 420 Joshua Lederberg Edward L.Tatum Frederick Sanger Chemistry Primary structure of proteins 54 *In a few cases,corecipients whose research was in an area outside of cell and molecular biology have been omitted from this list. **Medicine and Physiology JWCL151_fm_i-xviii.qxd 8/7/09 8:54 PM Page i This online teaching and learning environment integrates the entire digital textbook with the most effective instructor and student resources to fi t every learning style. 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JWCL151_fm_i-xviii.qxd 8/7/09 8:54 PM Page iii 6 th edition Cell and Molecular Biology Concepts and Experiments Gerald Karp John Wiley & Sons, Inc. JWCL151_fm_i-xviii.qxd 8/7/09 8:54 PM Page iv ACQUISITIONS EDITOR Kevin Witt PROJECT EDITOR Merilatt Staat SR.PRODUCTION EDITOR Patricia McFadden MARKETING MANAGER Ashaki Charles SENIOR PHOTO EDITOR Hilary Newman SENIOR DESIGNER Madelyn Lesure ILLUSTRATION EDITOR Anna Melhorn ILLUSTRATIONS Imagineering,Inc. MEDIA EDITOR Linda Muriello COVER PHOTO From Shigeo Takamori et al.,courtesy of Reinhard Jahn of the Max-Planck Institute for Biophysical Chemistry,Cell127:841,2006. PRODUCTION SERVICES Furino Production This book was set in 10.5/12 Adobe Caslon by Aptara,and printed and bound by RR Donnelley.The cover was printed by RR Donnelley. This book is printed on acid free paper. Copyright © 2010 John Wiley & Sons,Inc.All rights reserved.No part of this publication may be reproduced,stored in a retrieval system or transmitted in any form or by any means,electronic, mechanical,photocopying,recording,scanning or otherwise,except as permitted under Sections 107 or 108 of the 1976 United States Copyright Act,without either the prior written permission of the Publisher,or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center,Inc.,222 Rosewood Drive,Danvers,MA 01923,website www.copyright.com.Requests to the Publisher for permission should be addressed to the Permissions Department,John Wiley & Sons,Inc.,111 River Street,Hoboken,NJ 07030-5774, (201)748-6011,fax (201)748-6008,website http://www.wiley.com/go/permissions. To order books or for customer service,please call 1-800-CALL WILEY (225-5945). ISBN-13 978-0-470-48337-4 Printed in the United States of America 10 9 8 7 6 5 4 3 2 1 JWCL151_fm_i-xviii.qxd 8/7/09 8:54 PM Page v About the Author G erald C. Karp received a bachelor’s degree gastrulation, and cell determination in slime molds. For from UCLA and a Ph.D. from the University 13 years,he taught courses in molecular,cellular,and devel- of Washington. He conducted postdoctoral opmental biology at the University of Florida. During this research at the University of Colorado Medical period, Gerry coauthored a text in developmental biology Center before joining the faculty at the University of with N.John Berrill and authored a text in cell and molec- Florida. Gerry is the author of numerous research articles ular biology. Finding it impossible to carry on life as both on the cell and molecular biology of early development. full-time professor and author, Gerry gave up his faculty His interests have included the synthesis of RNA in early position to concentrate on writing. He hopes to revise this embryos, the movement of mesenchyme cells during text every three years About the Cover A molecular model of the membrane of a synaptic in green. The image on the back cover shows the surface vesicle. Within nerve cells, a synaptic vesicle structure of an intact vesicle.Most of the proteins present in consists of a cellular membrane surrounding a this membrane are required for the interaction of the vesicle soluble compartment filled with neurotransmit- with the plasma membrane. The large blue protein at the ter molecules.Vesicles of this type are assembled in the vicin- lower right of the vesicle contains a ring of subunits that ity of a nerve cell’s nucleus and then transported to the tip of rotates within the lipid bilayer as the protein pumps hydrogen the axon. There the vesicle awaits the arrival of a nerve ions into the vesicle. The elevated concentration of hydro- impulse that will induce it to fuse with the overlying plasma genions within the vesicle is subsequently used as an energy membrane, releasing its contents into the narrow cleft that source for the uptake of neurotransmitter molecules from the separates the nerve cell from a neighboring cell.The three- surrounding cytosol.These images provide the most compre- dimensional model of this membrane was constructed using hensive model of any cellular membrane yet to be studied known structures of the various proteins along with informa- and they reveal how much this membrane is dominated by tion on their relative numbers obtained from the analysis of protein—both within the bilayer itself and on both mem- purified synaptic vesicles. The image on the front cover brane surfaces. (From Shigeo Takamori et al., courtesy of shows a synaptic vesicle that has been cut in half; the lipid Reinhard Jahn of the Max-Planck Institute for Biophysical bilayer that forms the core of the vesicle membrane is shown Chemistry,Cell 127:841,2006.) JWCL151_fm_i-xviii.qxd 8/7/09 8:54 PM Page vi To Patsy and Jenny