Cold Spring Harbor Symposia on Quantitative Biology

COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY

VOLUME LVII COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY

VOLUME LVII

The Cell Surface

COLD SPRING HARBOR LABORATORY PRESS 1992 COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY VOLUME LVII 1992 by The Cold Spring Harbor Laboratory Press International Standard Book Number 0-87969-063-1 (cloth) International Standard Book Number 0-87969-064-X (paper) International Standard Serial Number 0091-7451 Library of Congress Catalog Card Number 34-8174

COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY

Founded in 1933 by REGINALD G. HARRIS Director of the Biological Laboratory 1924 to 1936

Previous Symposia Volumes

I (1933) Surface Phenomena xxvII (1962) Basic Mechanisms in Animal Virus Biology II (1934) Aspects of Growth XXVIII (1963) Synthesis and Structure of Macromolecules III (1935) Photochemical Reactions XXIX (1964) Human Genetics IV (1936) Excitation Phenomena XXX (1965) Sensory Receptors V (1937) Internal Secretions XXXI (1966) The Genetic Code VI (1938) Protein Chemistry XXXII (1967) Antibodies VII (1939) Biological Oxidations XXXIII (1968) Replication of DNA in Microorganisms VIII (1940) Permeability and the Nature of Cell Membranes XXXIV (1969) The Mechanism of Protein Synthesis IX (1941) Genes and Chromosomes: Structure and Organi- XXXV (1970) Transcription of Genetic Material zation XXXVI (1971) Structure and Function of Proteins at the X (1942) The Relation of Hormones to Development Three-dimensional Level XI (1946) Heredity and Variation in Microorganisms XXXVII (1972) The Mechanism of Muscle Contraction XII (1947) Nucleic Acids and Nucleoproteins XXXVIII (1973) Chromosome Structure and Function XIII (1948) Biological Applications of Tracer Elements XXXIX (1974) Tumor Viruses XIV (1949) Amino Acids and Proteins XL (1975) The Synapse XV (1950) Origin and Evolution of Man XLI (1976) Origins of Lymphocyte Diversity XVI (1951) Genes and Mutations XLII (1977) Chromatin XVII (1952) The Neuron XLIII (1978) DNA: Replication and Recombination XVIII (1953) Viruses XLIV (1979) Viral Oncogenes XIX (1954) The Mammalian Fetus: Physiological Aspects of XLV (1980) Movable Genetic Elements Development XLVI (1981) Organization of the Cytoplasm XX (1955) Population Genetics: The Nature and Causes of XLVII (1982) Structures of DNA Genetic Variability in Population XLVIII (1983) Molecular Neurobiology XXI (1956) Genetic Mechanisms: Structure and Function XLIX (1984) Recombination at the DNA Level XXII (1957) Population Studies: Animal Ecology and De- L (1985) Molecular Biology of Development mography LI (1986) Molecular Biology of Homo sapiens XXIII (1958) Exchange of Genetic Material: Mechanism and LII (1987) Evolution of Catalytic Function Consequences LIII (1988) Molecular Biology of Signal Transduction XXIV (1959) Genetics and Twentieth Century Darwinism LIV (1989) Immunological Recognition XXV (1960) Biological Clocks LV (1990) The Brain XXVI (1961) Cellular Regulatory Mechanisms LVI (1991) The Cell Cycle

Front Cover (Paperback): Ablation of neurons at the optic chiasm prevents growth of axons of retinal ganglion cells into the optic chiasm. (For details, see Reichardt et al., p. 426, this volume.) Back Cover (Paperback): Agrin-transfected cells induce clustering of AChRs. (For details, see Campanelli et al., p. 467, this volume.) Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Cold Spring Harbor Laboratory for libraries and other users registered with the Copyright Clearance Center (CCC) Transactional Reporting Service, provided that the base fee of $3.00 per article is paid directly to CCC, 21 Congress St., Salem MA 01970. [0-87969-063-1/92 $3.00 + .00]. This consent does not extend to other kinds of copying, such as copying for general distribution, for advertising or promotional purposes, for creating new collective works, or for resale. All Cold Spring Harbor Laboratory Press publications may be ordered directly from Cold Spring Harbor Laboratory Press, 10 Skyline Drive, Plainview, New York 11803. Phone: 1-800-843-4388 (Continental U.S. and Canada); (516)349-1930 (All other locations). FAX: (516)349-1946. Symposium Participants

ADIE, ELAINE, Dept. of Biochemistry, University Molecular Medicine, Howard Hughes Medi- of Glasgow, Scotland cal Institute, University of California, San AGER, ANN, Dept. of Celt and Structural Biolo- Diego gy, University of Manchester, United BmNBAUMER, LUTZ, Dept. of Cell Biology, Kingdom Baylor College of Medicine, Houston, AKESON, RICHARD, Dept. of Basic Science Re- Texas search, Children's Hospital Research Foun- BIRNBAUMER, MARIEL, Dept. of Cell Biology, dation, Cincinnati, Ohio Baylor College of Medicine, Houston, ALTSCHULER, DANIEL, Dept. of Cell Biology, Texas Burroughs Wellcome Co., Research Tri- BLOBEL, GUNTER, Howard Hughes Medical Insti- angle Park, North Carolina tute, Rockefeller University, New York, AMANN, EGON, Pharma Research Laboratories, New York Hoechst Japan, Ltd., Kawagoe-Saitama, BLOOM, THEODORA, Nature, London, United Japan Kingdom ANDERSON, KATHRYN, Dept. of Molecular and BONHOEFFER, FRIEDRICH,Abteilung Physikalische Cell Biology, University of California, Ber- Biologie, Max Planck Institute, Tubingen, keley Germany ANDERSON, RICHARD, Dept. of Cell Biology and BOOTH, PAUL, Dept. of Cellular Biochemistry, Neuroscience, University of Texas South- Life Technologies Inc., Gaithersburg, western Medical Center, Dallas Maryland APPLEBURY, MEREDITH, Eye Research Laborator- BORST, JANNIE, Dept. of Immunology, Nether- ies, University of Chicago, Illinois lands Cancer Institute, Amsterdam, The ARTAVANIS-TsAKONAS, SPYRIDON, Dept. of Molec- Netherlands ular and Developmental Neurobiology, BossY, BLAISE, Howard Hughes Medical Insti- Boyer Center for Molecular Medicine, Yale tute, University of California, San Francisco University, New Haven, Connecticut BOURNE, HENRY, Department of Pharmacology, ASHKENAZI, AVI, Dept. of Molecular Biology, University of California, San Francisco Genentech, Inc., South San Francisco, Cali- BRANDLEY, BRIAN, Glycomed Inc., Alameda, fornia California ATTISANO, LILLIAN, Dept. of Cell Biology, Me- BRONSON, RICHARD, Dept. of Obstetrics and morial Sloan-Kettering Cancer Center, New Gynecology, State University of New York, York, New York Stony Brook AXLE, RICHARD, Howard Hughes Medical Insti- BROWN, ABRAHAM, Lederle Laboratory, Pearl tute, Columbia University, New York, New River, New York York BROWN, MICHAEL, Center for Genetic Disease, BAUER, MARGARET, Dept. of Medical Microbiol- University of Texas Southwestern Medical ogy and Immunology, University of Wiscon- Center, Dallas sin, Madison BROWNING, JEFFREY, Dept. of Cell Biology, BEKKERS, AUGUST, Dept. of Enzymology and Biogen, Cambridge, Massachusetts Protein Engineering, Institute of Biomem- BRUGGE, JOAN, Dept. of Microbiology, Universi- branes, Utrecht, The Netherlands ty of Pennsylvania School of Medicine, Phil- BELL, GREGORY, Dept. of Medicine, University adelphia of California, San Francisco BURLtNGAME, A.L., Dept. of Pharmaceutical BERSTEIN, GABRIEL, Dept. of Pharmacology, Chemistry, University of California, San University of Texas Southwestern Medical Francisco Center, Dallas BURNETT, J. PAUL, Dept. of Molecular and Cell BEVlLACQUA, MICHAEL, Dept. of Cellular and Biology Research, Lilly Research Labora- vi SYMPOSIUM PARTICIPANTS

tories, Lilly Corporate Center, Indianapolis, Molecular Pathology, Merck Research Lab- Indiana oratories, Rahway, New Jersey BURRIDGE, KEITH, Dept. of Cell Biology and DEVREOTES, PETER, Dept. of Biological Chemis- Anatomy, University of North Carolina, try, Johns Hopkins Medical School, Balti- Chapel Hill more, Maryland BYTH, KATE, Dept. of Immunology and Pathol- DICKESON, KENT, Dept. of Biotechnology and ogy, Cambridge University, United Microbiology, Wyeth-Ayerst Research, Kingdom Radnor, Pennsylvania CAMPBELL, BOB, Ares Advanced Technology, DILIBERTO, EMANUEL, Dept. of Medical Bio- Randolph, Massachusetts chemistry, Burroughs Wellcome Co., Re- CARAS, INGRID, Dept. of Immunobiology, search Triangle Park, North Carolina Genentech, Inc., South San Francisco, Cali- DILORENZO, TERESA, Dept. of Otolaryngology, fornia Long Island Jewish Medical Center, New CARMELIET, PETER, Whitehead Institute, Cam- Hyde Park, New York bridge, Massachusetts DRICKAMER, KURT, Dept. of Biochemistry and CARPEN, OLLI, Dept. of Pathology, University of Molecular Biophysics, Columbia University, Helsinki, Finland New York, New York CATTERALL, CATHERINE, Dept. of Inflammation DUDLEY, DAVID, Signal Transduction, Parke- Biology, CellTech Ltd., Slough, Berkshire, Davis Pharmaceutical Corp., Ann Arbor, United Kingdom Michigan CHAN, Po-YING, Dept. of Cellular Interactions, EDELMAN, GERALD, Dept. of Developmental and Bristol-Myers Squibb PRI, Seattle, Molecular Biology, Rockefeller University, Washington New York, New York CHANG, CHIA-PING, School of Medicine, Uni- EINSTEIN, RICHARD, Dept. of Molecular Ge- versity of California at San Diego, La Jolla netics, SmithKline Beecham, King of Prus- CHANG, XIO-JIA, Dept. of Cell Adhesion Pro- sia, Pennsylvania teins, Genetics Institute, Cambridge, Massa- ENDEMANN, GERDA, Scios, Inc., Mountain View, chusetts California CHARDIN, PIERRE, CNRS-Institut de Pharmacol- FARRELL, FRANCIS, Dept. of Cell Biology, Bur- ogie, Valbonne, France roughs Wellcome Co., Research Triangle CHEN, MANN-JY, Dept. of Microbiology and Im- Park, North Carolina munology, Jefferson Cancer Institute, Phila- FAULDS, DARYL, Dept. of Cell Biology and Im- delphia, Pennsylvania munology, Berlex Biosciences, South San CHERESH, DAVID, Dept. of Immunology, Scripps Francisco, California Clinic and Research Foundation, La Jolla, FEATHERSTONE, CAROL, Trends in Cell Biology, California Cambridge, United Kingdom CHU, KETING, Dept. of Microbiology and Immu- FIRTEL, RICHARD, Dept. of Biology, Center for nology, University of California, San Fran- Molecular Genetics, University of California cisco at San Diego, La Jolla CLARK, CHRIS, Dept. of Genetics, Stanford Uni- FISKIN, MAX, Dept. of Microbiology, Kansas versity, Stanford, California University Medical Center, Kansas City COUEZ, DOMINIQUE, Dept. of Cellular Biochem- FLEISSNER, ERWIN, Div. of Science and Mathe- istry and Immunology, SmithKline Beech- matics, Hunter College, City University of am, King of Prussia, Pennsylvania New York, New York COUGHLIN, SHAUN, Department of Medicine, FRANKE, WERNER, Institute of Cell and Tumor Cardiovascular Research Institute, Universi- Biology, German Cancer Research Center, ty of California, San Francisco Heidelberg, Germany CRESSWELL, PETER, Dept. of Immunobiology, FRASER, IAN, Dunn School of Pathology, Oxford Howard Hughes Medical Institute, Yale University, Oxford, United Kingdom University School of Medicine, New Haven, FREMEAU, BOB, Dept. of Neurobiology, Duke Connecticut University Medical Center, Durham, North DANIELS, ALEJANDRO, Dept. of Pharmacology, Carolina Burroughs Wellcome Co., Research Tri- FURTH, MARK, Dept. of Molecular and Cell Biol- angle Park, North Carolina ogy, Regeneron Pharmaceuticals, Inc., Tar- DEMARTINO, JULIE, Dept. of Biochemical and rytown, New York SYMPOSIUM PARTICIPANTS vii

GALAKATOS, NICHOLAS, Pharmaceuticals, Ciba- HEIDARAN, MOHAMMAD, National Cancer Insti- Geigy Corp., Summit, New Jersey tute, Bethesda, Maryland GARBERS, DAVID, Dept. of Pharmacology, How- HELPER, JOHN, Dept. of Pharmacology, Universi- ard Hughes Medical Institute, University of ty of Texas Southwestern Medical Center, Texas Southwestern Medical Center, Dallas DalLas GEIGE~, BENJAMIN, Dept. of Chemical Immunol- HEMLER, MART~N, Dept. of Tumor Virology, ogy, Weizmann Institute of Science, Re- Dana-Farber Cancer Institute, Boston, hovot, Israel Massachusetts GERARD, CRAIG, Dept. of Pediatrics, Children's HEMPERLY, JOHN, Dept. of Neurobiology, Becton Hospital, Boston, Massachusetts Dickinson Co., Research Triangle Park, GERTLER, FRANK, Dept. of Oncology, University North Carolina of Wisconsin, Madison HEN, RENE, LGME de CNRS, Strasbourg, GILMAN, ALFRED, Dept. of Pharmacology, Uni- France versity of Texas Southwestern Medical Cen- HENDRICKSON, WAYNE, Dept. of Biochemistry ter, Dallas and Molecular Biophysics, Columbia Uni- GINSBERG, MARK, Dept. of Immunology, Scripps versity, New York, New York Clinic and Research Foundation, La Jolla, HEPLER, JOHN, Dept. of Pharmacology, Universi- California ty of Texas, Dallas GOLDSTEIN, JOSEPH, Dept. of Molecular Ge- HETZEL, DONALD, Corporate Research and De- netics, University of Texas Southwestern velopment, Becton Dickinson and Co., Medical Center, Dallas Franklin Lakes, New Jersey GOMPERTS, MIRANDA, Wellcome CRL Institute, HIGGINS, LINDA, Dept. of Cell Biology, Scios, University of Cambridge, United Kingdom Inc., Mountain View, California GOODMAN, COREY, Dept. of Molecular and Cell HINCK, LINDSAV, Dept. of Molecular and Cell Biology, Howard Hughes Medical Institute, Physiology, Stanford University, Stanford, University of California, Berkeley California GUREVICH, VSEVOLOD, Dept. of Pharmacology, HOBART, PETER, Dept. of Molecular Genetics, Thomas Jefferson University, Philadelphia, Pfizer Central Research, Groton, Connec- Pennsylvania ticut HAAG, FR1EDRICH, Dept. of Clinical Immunol- HOLGERSSON, JAN, Dept. of Molecular Biology, ogy, University Hospital, Hamburg, Massachusetts General Hospital, Boston Germany HORVITZ, H. ROBERT, Dept. of Biology, Howard HADINGHAM, KAREN, Dept. of Biochemistry, Hughes Medical Institute, Massachusetts In- Merck Sharp and Dohme Research Lab- stitute of Technology, Cambridge oratories, Harlow, Essex, United Kingdom Hsv, YEN-MING, Dept. of Protein Chemistry, HARRISON, STEPHEN, Dept. of Biochemistry and Biogen Research Corp., Cambridge, Massa- Molecular Biology, Harvard University, chusetts Cambridge, Massachusetts Hu, SYLVIA, Mammalian Cell Research, Amgen, HATTORI, YUTAKA, Dept. of Genetics, National Inc., Thousand Oaks, California Cancer Center Research Institute, Chou- HUNTER, TONY, Dept. of Molecular Biology and Ku, Tokyo, Japan Virology, Salk Institute for Biological Sci- HAWKINS, PHILIP, Dept. of Biochemistry, AFRC ences, La Jolla, California Institute of Animal Physiology and Genetics HUTCHCROFT, JILL, Dept. of Medicinal Chemistry Research, Cambridge, United Kingdom and Pharmacology, Purdue University, West HAYASHI, MASAO, Dept. of Biology, Ochanomizu Lafayette, Indiana University, Bunkyo-ku, Tokyo, Japan HYNES, RICHARD, Dept. of Biology, Center for HEDMAN, HAKAN, Unit for Applied Cell and Cancer Research, Massachusetts Institute of Molecular Biology, University of Umea, Technology, Cambridge Sweden IMBODEN, JOHN, Dept. of Medicine, University of HEDmCK, LORA, Dept. of Oncology and Pathol- California, San Francisco ogy, Johns Hopkins School of Medicine, IWASHITA, SHINTARO, Dept. of Cellular Biochem- Baltimore, Maryland istry, Mitsubishi-Kasei Institute of Life Sci- HEEMELS, THERESE, Dept. of Cellular Biochemis- ences, Machida-shi, Tokyo, Japan try, The Netherlands Cancer Institute, Am- IZUMO, SEIGO, Dept. of Molecular Medicine, sterdam, The Netherlands Beth Israel Hospital, Boston, Massachusetts viii SYMPOSIUM PARTICIPANTS

JACKSON, TREVOR, Dept. of Biochemistry, AFRC California Pacific Medical Center, San Fran- Institute of Animal Physiology and Genetic cisco Research, Cambridge, United Kingdom LAMPUGNANI, MARIA GRAZIA, Dept. of Vascular JACOBSON, KEN, Dept. of Cell Biology and Biology, Mario Negri Institute, Milan, Italy Anatomy, University of North Carolina, LANG, RICHARD, G.W. Hooper Research Foun- Chapel Hill dation, University of California, San Fran- JAIN, NEERAJ, Centre for Cellular and Molecular cisco Biology, Hyderabad, India LANGNER, KLAuS-DIETER, Preclinical Research, JAN, LILY, Howard Hughes Medical Institute, Behringwerke AG, Marburg/Lahn, Ger- University of California, San Francisco many JANIS, RICHARD, Dept. of Corporate Molecular LAROSA, GREGORY, Dept. of Molecular Biology, Biology, Abbott Laboratories, Abbott Park, Repligen Corp., Cambridge, Massachusetts Illinois LASKY, LAURENCE, Genentech, Inc., South San JAVAHERIAN, KASHI, Dept. of Molecular Biology, Francisco, California Repligen Corp., Cambridge, Massachusetts LEAHY, DAN, Dept. of Biochemistry, Columbia JESSELL, THOMAS, Center for Neurobiology and University, New York, New York Behavior, Columbia University College of LEE, CHONG-CHOU, Dept. of Developmental Physicians & Surgeons, New York, New Biology, National Institutes of Health, York Bethesda, Maryland JONES, GARETH, Biological Spectroscopy, Serc LEE, MONG-HONG, Dept. of Biological Sciences, Daresbury Laboratory, Warrington, Che- University of Pittsburg, Pennsylvania shire, United Kingdom LEFKOWITZ, ROBERT, Department of Medicine, KANDEL, ERIC, Center for Neurobiology and Be- Duke University Medical Center, Durham, havior, Columbia University College of Phy- North Carolina sicians & Surgeons, New York, New York LEHTO, VELI-PEKKA, Dept. of Pathology, Uni- KAWAHARA, DOUGLAS, Advanced Cellular Biolo- versity of Oulu, Finland gy, Becton Dickinson, San Jose, California LEVI, GIOVANNI, Physiopathologie du Develope- KIM, SUNG-HOU, Dept. of Chemistry, Lawrence ment, C.N.R.S., Paris, France Berkeley Laboratory, University of Califor- LEVIN, MARGARET, Dept. of Biological Sciences, nia, Berkeley University of Pittsburgh, Pennsylvania KIMBLE, JUDITH, Dept. of Molecular Biology, LI, JIANXUN,Dept. of Signal Transduction, Rock- University of Wisconsin, Madison efeller University, New York, New York KINTNER, CHRIS, Dept. of Molecular Neuro- LI, MIN, Howard Hughes Medical Institute, Uni- biology, The Salk Institute for Biological versity of California, San Francisco Sciences, San Diego, California LIMBIRD, LEE, Dept. of Pharmacology, Van- KLEIN, PETER, Dept. of Biochemistry and Mo- derbilt University School of Medicine, lecular Biology, Harvard University, Cam- Nashville, Tennessee bridge, Massachusetts LING, LEONA, Dept. of Molecular Biology, KOLANUS, WALDEMAR,Dept. of Molecular Biolo- Biogen, Inc., Cambridge, Massachusetts gy, Massachusetts General Hospital, Boston LID, YAFANG, Dept. of Pharmacology, McGill KOSHLAND, DANIEL, Dept. of Molecular and Cel- University, Montreal, Quebec, Canada lular Biology, University of California, Ber- LODISH, HARVEY, Whitehead Institute, Mas- keley sachusetts Institute of Technology, Cam- KRAMER, HELMUT, Dept. of Biological Chemis- bridge try, School of Medicine, University of Cali- LOMEDICO, PETER, Dept. of Molecular/Cellular fornia, Los Angeles Biology and Biochemistry, Hoffmann- KRIEGER, MONTY, Dept. of Biology, Massachu- LaRoche & Co., Ltd., Nutley, New Jersey setts Institute of Technology, Cambridge LOOR, FRANCIS, Preclinical Research, Sandoz KUBLER, DIETER, Dept. of Pathochemistry, Ger- Pharma, Ltd., Basel, Switzerland man Cancer Research Center, Heidelberg LOWE, DAVID, Dept. of Molecular Biology, KUHSTOSS, STUART, Natural Products Research, Genentech, Inc., South San Francisco, Cali- Eli Lilly & Co., Indianapolis, Indiana fornia KUROSAKI, TOMOH1RO, Dept. of Biochemical MAGEE, ANTHONY, Dept. of Eukaryotic Mo- Genetics, Memorial Sloan-Kettering Cancer lecular Genetics, National Institute of Medi- Institute, New York, New York cal Research, Mill Hill, London, United KUSHNER, PINKY DROSTEN, ALS Research Ctr., Kingdom SYMPOSIUM PARTICIPANTS ix

MARcO-MAGAZIN, MARILYN, Protein Chemistry NELSON, W. JAMES, Dept. of Molecular and Cell Unit, Sanofi ELF Bio Recherches, Labege- Physiology, Stanford University School of Innopole Vole, France Medicine, Stanford, California MASSAGUI~, JOAN, Dept. of Cell Biology, Ge- NEUBERT, THOMAS, Dept. of Biochemistry, How- netics Program, Memorial Sloan-Kettering ard Hughes Medical Institute, University of Cancer Center, New York, New York Washington, Seattle MCALMON, KAREN, Dept. of Neonatology, Chip NIESSEN, CARIEN, Dept. of Immunohematology, dren's Hospital, Boston, Massachusetts Central Laboratory of Blood Tranfusion McCAFFREY, PATRICIA,Dept. of Tumor Virology, Ser., Amsterdam, The Netherlands Dana-Farber Cancer Institute, Boston, NIGAM, SANJAY, Dept. of Medicine, Harvard Massachusetts Medical School, Brigham & Women's Hos- MCMAHON, ANDY, Dept. of Cell and Develop- pital, Boston, Massachusetts mental Biology, Roche Institute of Mo- NITABACH, MICHAEL, Dept. of Biological Sci- lecular Biology, Nutley, New Jersey ences, Columbia University, New York, MCNEILL, HELEN, Dept. of Molecular and Cel- New York -" lular Physiology, Stanford University, Stan- NOLTE, FREDRICK, Dept. of Immunology, Uni- ford, California versity Hospital, First Medical Clinic, Ham- MIAKE-LYE, RYN, Cell, Cambridge, Massachu- burg, Germany setts NORDMANN, RENE, Preclinical Research, Sandoz MILLER, LINDA, Science, Washington, D.C. Pharma, Ltd., Basel, Switzerland MILLER, R. TYLER, Dept. of Internal Medicine, NORTH, GEOFFREY, Current Biology, London, University of Texas Southwestern Medical United Kingdom Center, Dallas NI~ISSLEIN-VOLHARD, CHRISTIANE, Max Planck In- MINAM1, YASUHIRO, Institute for Molecular and stitut fur Entwicklungsbiologie, Tubingen, Cellular Biology, Osaka University, Suita- Germany shi, Osaka, Japan OFFORD, JIM, Dept. of Biotechnology, Parke- MOOLENAAR, WOUTER, Dept. of Cellular Bio- Davis, Ann Arbor, Michigan chemistry, Netherlands Cancer Institute, OHANJAN, VASKEN,Dept. of Medicine, Universi- Amsterdam ty of Manchester, United Kingdom MOSCHUETZKY, HEINZ, Max Planck Institute, OMER, CHARLES, Dept. of Cancer Research, Freiburg, Germany Merck Research Laboratories, West Point, MURPHY, CHRISTINE, Dept. of Pharmacology, Pennsylvania University of Bath, Avon, United Kingdom ORTEGA, EDWARDO, Dept. of Geographic Medi- MURPHY-ERDOSH, CYNTHIA, Dept. of Neuro- cine, New England Medical Center, Boston, science, Howard Hughes Medical Institute, Massachusetts University of California, San Francisco OZENBERGER, BRAD, American Cyanamid Co., MUSIL, LINDA, Dept. of Anatomy and Cellular Princeton, New Jersey Biology, Harvard Medical School, Boston, PAHLSSON, PETER, Dept. of Pathology, University Massachusetts of Pennsylvania, Philadelphia MUTA, TATSUSHI, Dept. of Biology, Faculty of PANDE, GOPAL, Dept. of Pathology, Harvard Medicine, Kyushu University, Higashi-Ku, Medical School, Boston, Massachusetts Fukuoka, Japan PAPKOFF, JACKIE, Dept. of Tumor Biology, Syn- MYNARCIK, DENNIS, Dept. of Endocrinol- rex Resarch, Palo Alto, California ogy, State University of New York, Stony PARADA, LUIS, Mammalian Genetics Section, Brook Frederick Cancer Research & Development NA, SONG-QING, Dept. of Biology, Brandeis Uni- Center, Frederick, Maryland versity, Waltham, Massachusetts PARKER, VANN, Dept. of Mammalian Cell and NAKANISHI, SHIGETADA,Institute of Immunology, Molecular Biology, Amgen, Inc., Thousand Faculty of Medicine, Kyoto University, Oaks, California Sakyo-ku, Kyoto, Japan PAUSCH, MARK, Agricultural Research Division, NAPIER, MARY, Dept. of Cardiovascular Re- American Cyanamid Co., Princeton, New search, Genentech, Inc., South San Francis- Jersey co, California PEACH, ROBERT, Dept. of Cellular Interactions, NASTUK, MARY, Dept. of Biology, Worcester Bristol-Myers Squibb Pharmaceuticals, Seat- Foundation for Experimental Biology, tle, Washington Shrewsbury, Massachusetts PELLETIER, ANTHONY, Dept. of Cell Genetics, x SYMPOSIUM PARTICIPANTS

Genentech, Inc., South San Francisco, Cali- RUOSLAHTI, ERKK1, La Jolla Cancer Research fornia Foundation, La Jolla, California PLOEGH, HIDDE, Netherlands Cancer Institute, SAAVEDRA, RAUL, Dept. of Skeletal Disorders, Amsterdam Harvard Medical School, Boston, Massa- POULIOT, YANNICK, Dept. of Muscle Biochemis- chusetts try, Montreal Neurological Institute, Mon- SANES, JOSHUA, Dept. of Anatomy and Neuro- treal, Quebec, Canada biology, Washington University School of PREMONT, RICHARD, Dept. of Pharmacology, Medicine, St. Louis, Missouri Mount Sinai School of Medicine, New York, SAWADA, IKUHISA, Dept. of Research and Plan- New York ning, Yamanouchi Pharmaceutical Co., QWARNSTROM, EVA, Dept. of Pathology, Uni- Ltd., Itabashi-ku, Tokyo, Japan versity of Washington, Seattle SCHELLER, RICHARD, Dept. of Biological Sci- RADICE, GLENN, Center for Cancer Research, ences, Stanford University, Stanford, Cali- Massachusetts Institute of Technology, fornia Cambridge SCHLESSINGER, JOSEPH, Dept. of Pharmacology, RALPH, LLOYD, Dept. of Pharmaceutics and New York University Medical Center, New Drug Delivery, Amgen, Inc., Thousand York, New York Oaks, California SCHUESSLER, PETRA, Dept. of Microbiology and RANDI, ANNA, Howard Hughes Medical Insti- Hygiene, Institut fur Medizinische, tute, Washington University School of Med- Freiburg, Germany icine, St. Louis, Missouri SCHUMACHER, TON, Dept. of Cellular Biochemis- REDDY, PRANHITHA, Dept. of Pharmacology, try, The Netherlands Cancer Institute, Am- University of Washington, Seattle sterdam REED, RANDALL,Dept. of Molecular Biology and SEAMAN, WILLIAM, Dept. of Medicine and Mi- Genetics, Johns Hopkins University, Balti- crobiology/Immunology, University of Cali- more, Maryland fornia, San Francisco REICHARDT, LOUIS, Howard Hughes Medical In- SEED, BRIAN, Dept. of Molecular Biology, Har- stitute, University of California, San Fran- vard Medical School, Massachusetts Gener- cisco al Hospital, Boston REYNOLDS, FREDERICK, Oncogene Science, Inc., SEEGER, ROBERT, Dept. of Hematology and On- Uniondale, New York cology, Childrens Hospital, Los Angeles, RIDLEY, ANNE, Dept. of Cell and Molecular Biol- California ogy, Institute of Cancer Research, London, SHARFE, NIGEL, Dept. of Immunology and Pa- United Kingdom thology, Cambridge University, Cambridge, ROBERTSON, MIRANDA, Garland Publishing, New United Kingdom York SHARIF, MOHAMMED, Dept. of Medical Biological RODER, JOIJN, Dept. of Molecular Immunology, Chemistry, University of California, Davis University of Toronto, Canada SHIH, AH-SHING, Dept. of Molecular Biology, RODRIGUES, MAURICIO, Dept. of Medical and Canji, Inc., San Diego, California Molecular Parasitology, New York Universi- SHISHIDO, TOMOYUKI, Dept. of Signal Transduc- ty School of Medicine, New York, New tion, Rockefeller University, New York, York New York ROMEO, CHARLES, Dept. of Molecular Biology, SHOWELL, HENRY, Dept. of Immunology and In- Massachussetts General Hospital, Boston fectious Disease, Pfizer Central Research, ROSENBERG, ROBERT, Dept. of Biology, Massa- Groton, Connecticut chusetts Institute of Technology, Cambridge SIEH, MONICA, Howard Hughes Medical Insti- ROSS, CHRISTOPHER, Dept. of Psychiatry and tute, University of California, San Francisco Neuroscience, Johns Hopkins University, SIMON, MELVIN, Dept. of Biology, California In- Baltimore, Maryland stitute of Technology, Pasadena RUBIN, BEATRIX, Brain Research Institute, Uni- SIMONS, KAI, Cell Biology Program, EMBL, versity of Zurich, Switzerland Heidelberg, Germany RUBIN, GERALD, Dept. of Molecular and Cell SIMPSON, PAT, Facult6 de M6decine, Laboratoire Biology, Howard Hughes Medical Institute, de Gdn6tique Moldculaire, Strasbourg, University of California, Berkeley France SYMPOSIUM PARTICIPANTS xi

SINGH, SUNIL, Affymax Research Institute, PaiD TEMPLE, GARY, Life Technologies, Inc., Gaith- Alto, California ersburg, Maryland SMRCKA, ALAN, Dept. of Pharmacology, Uni- THE1BERT, ANNE, Neurobiology Research Cen- versity of Texas Southwestern Medical Cen- ter, University of Alabama, Birmingham ter, Dallas THIELE, HEINz-GuNTHER, Dept. of Immunology, SONG, ZHIWEI, Dept. of Biological Chemistry, University of Hamburg, Germany University of Michigan, Ann Arbor THORNER, JEREMY, Dept. of Molecular and Cell SPALDING, TRACY, Dept. of Physical Chemistry, Biology, University of California, Berke- National Institute for Medical Research, ley London, United Kingdom TOLSTRUP, ANNE, Dept. of Molecular Biology, SPRINGER, TIMOTHY, Center for Blood Research, University of Aarhus, Denmark Harvard Medical School, Boston, Massa- TONEGAWA, SUSUMU, Center for Cancer Re- chusetts search, Massachusetts Institute of Technolo- STASSEN, FRANS, Research Dept., CIBA-GEIGY gy, Cambridge Pharmaceuticals, Summit, New Jersey TONKS, NICHOLAS, Cold Spring Harbor Labora- STEPHENS, LEN, Dept. of Biochemistry, AFRC tory, Cold Spring Harbor, New York Institute of Animal Physiology and Genetics TROPAK, MICHAEL, Dept. of Immunology and Research, Cambridge, United Kingdom Neurobiology, Mt. Sinai Hospital Research STERNBERG, PAUL, Dept. of Biology, California Center, University of Toronto, Ontario, Institute of Technology, Pasadena Canada STILLMAN, BRUCE, Cold Spring Harbor Labora- TSYGANKOV, ALEXANDER, Dept. of Molecular tory, Cold Spring Harbor, New York Biology, Bristol Meyers Squibb Research STROPP, UDO, Dept. of Biotechnology, Central Institute, Princeton, New Jersey Research, Bager-AG, Leverkusen, Ger- TUCKER, GORDON, Institut de Recherches Ser- many vier, Suresnes, France STRYER, LUBERT, Dept. of Cell Biology, Stanford TYRRELL, DAVID, Dept. of Biochemistry, University School of Medicine, Stanford, Glycomed, Inc., Alameda, California California UNANUE, EMIL, Dept. of Pathology, Washington SUDHOF, THOMAS, Dept. of Molecular Genetics, University School of Medicine, St. Louis, University of Texas Southwestern Medical Missouri Center, Dallas VAN DAMME, HENK, Dept. of Medical Biochemis- SUZUKI, SHINTARO,Dept. of Ophthalmology and try, University of Leiden, The Netherlands Microbiology, Doheny Eye Institute, Uni- VAN HUIJSDUIJNEN, R. HOOFT, Glaxo I.M.B., versity of Southern California School of Geneva, Switzerland Medicine, Los Angeles VAN NOESEL, CAREL, Clinical Viro Immunology, SWIMMER, CANDACE, ImmunoGen, Inc., Cam- Central Laboratory of Blood Transfusion, bridge, Massachusetts Amsterdam, The Netherlands TAKEICHI, MASATOSHI,Dept. of Biophysics, Fa- VAN SCHRAVENDIJK,MARIE ROSE, Dept. of Infec- culty of Science, Kyoto University, Sakyo- tious Diseases, DNA Research Institute, ku, Kyoto, Japan Palo Alto, California TAKUM1, TORU, Whitehead Institute for Biomedi- VARTICOVSKI,LYUBA, Dept. of Medical Research, cal Research, Cambridge, Massachusetts Tufts University School of Medicine, Bos- TAN, AGNES, Dept. of Cellular Biochemistry, ton, Massachusetts The Netherlands Cancer Institute, Am- VICENTINI, LUCIA, Dept. of Pharmacology, Uni- sterdam versity of Milan, Italy TANAKA, TOSHIAKI, Dept. of Tumor Immunol- VILLAFRANCA, J. ERNEST, Dept. of Protein En- ogy, Dana-Father Cancer Institute, Boston, gineering, Agouron Pharmaceuticals, Inc., Massachusetts San Diego, California TANG, WEI JEN, Dept. of Pharmacology, Uni- VILLANO, JOHN, Dept. of Biochemistry, Universi- versity of Texas Southwestern Medical Cen- ty of Texas Southwestern Medical Center, ter, Dallas Dallas TEIXEIRA, A., Dept. of Medical Oncology, Im- VOGELI, GABRIEL, Dept. of Molecular Biology, perial Cancer Research Fund, London, Upjohn Co., Kalamazoo, Michigan United Kingdom WALSH, FRANK, Dept. of Experimental Pathol- xii SYMPOSIUM PARTICIPANTS

ogy, Guy's Hospital, London, United WILLIAMS, LEWIS, Dept. of Cardiovascular Re- Kingdom search, University of California, San Fran- WANG, SY-SHI, Biomembrane Institute, Seattle, cisco Washington WITUNSKI, MICHAEL, Kiawah Island, South WARD, REBECCA, Research Dept., Genentech, Carolina Inc., South San Francisco, California WONG, WINNIE, Dept. of Biochemistry, BASF WARD, S., Dept. of Pharmacology and Phar- Bioresearch Corp., Cambridge, Massachu- macy, University of Bath, Avon, United setts Kingdom WONG, YEE WAH, Dept. of Physiology and Bio- WATSON, STEVE, Dept. of Pharmacology, Oxford physics, Columbia University, New York, University, Oxford, United Kingdom New York WATT, SUSANNE, Dept. of Medical Oncology, WRANA, JEFFREY, Dept. of Cell Biology and Imperial Cancer Research Fund, West Smith- Genetics, Memorial Sloan-Kettering Cancer field, United Kingdom Center, New York, New York WATT, TERRI, Dept. of Osteobiology, Research WRIGHT, CLIFFORD, Dept. of Immunopathology, and Development, Boehringer Mannheim, Parke Davis Pharmacology Research, Ann Indianapolis, Indiana Arbor, Michigan WEAVER, CHRISTINA, Dept. of Neuroscience, Wu, MIN, Center for Cancer Research, Massa- University of California, San Francisco chusetts Institute of Technology, Cambridge WEINMASTER, GERRY, Dept. of Neurobiology, XlE, MINGSHENG, Dept. of Physiology, Columbia Salk Institute, San Diego, California University, New York, New York WEIS, WILLIAM, Dept. of Biochemistry and Mo- Xu, HuA, Dept. of Microbiology, University of lecular Biophysics, Columbia University, California, San Francisco New York, New York YAMADA, KENNETH M., Lab. of Developmental WEISS, ARTHUR, Howard Hughes Medical Insti- Biology, National Institute of Dental Re- tute, University of California, San Francisco search, National Institutes of Health, WEISSMAN, IRVING, Dept. of Pathology, Lab. of Bethesda, Maryland Experimental Oncology, Stanford Universi- YAMAGATA, MASAHITO, Dept. of Anatomy and ty Medical Center, Stanford, California Neurobiology, Washington University, St. WESSENDORF, LISA, Dept. of Molecular Biology, Louis, Missouri Medical Research Council, Cambridge, YAMAMOTO, KYOHEI, Dept. of Cell Biology, Bur- United Kingdom roughs Wellcome Co., Research Triangle WESTMACOTT, DON, Dept. of Anti-Inflammatory Park, North Carolina Biology, Roche Products, Ltd., Hertford- YANCOPOULOS, GEORGE, Regeneron Phar- shire, United Kingdom maceuticals, Inc., Tarrytown, New York WETZEL, RONALD, Dept. of Macromolecular Sci- YANG, Yu-CHUNG, Dept. of Medicine and Hema- ences, SmithKline Beecham, King of Prus- tology/Oncology, Indiana University School sia, Pennsylvania of Medicine, Indianapolis WHEELER, GRANT, Center for Cancer Research, YOSHIHARA, YOSHIHIRO, Dept. of Neuroscience, Massachusetts Institute of Technology, Osaka Bioscience Institute, Suita, Osaka, Cambridge Japan WIESCHAUS, ERIC, Dept. of Molecular Biology, Yu, QIANG, Pulmonary Center, Boston Universi- Princeton University, Princeton, New Jersey ty School of Medicine, Boston, Massachu- WILEY, DON, Dept. of Biochemistry and Mol- setts ecular Biology, Harvard University, Cam- YUAN, JUNYING, Cardiovascular Research Cen- bridge, Massachusetts ter, Massachusetts General Hospital, Charles- WILKIE, THOMAS, Div. of Biology, California In- town stitute of Technology, Pasadena ZIPURSKY, LARRY, Dept. of Biological Chemistry, WILLERT, KARL, Dept. of Microbiology and Im- University of California, Los Angeles munology, University of California, San ZOLNIEROWICZ, STANISLAW, Friedrich Miescher Francisco Institute, Basel, Switzerland WILLIAMS, CAROL, Dept. of Immunology, Mayo Clinic, Rochester, Minnesota First row: M. Brown; Picnic Second row: D. Leahy, K. Drickamer, R. Anderson; H.R. Horvitz, B. Stillman, D. Luke III Third row: A. Ager, G. Jones; C. Goodman, L. Reichardt Fourth row: Picnic; T. Springer i 84184, 9 ~

First row: A. Ager, J. Witkowski, G. Jones, F. Walsh; M. Mathews, R. Hynes Second row: B. Stillman, J. Kimble; H. Lodish, J. Goldstein Third row: A. Tolstrup; M. Simon; R. Scheller First row: J. Schlessinger, W. Moolenaar; R. Anderson, K. Simons Second row: R. Miake-Lye, C. Kintner; S.-H. Kim, P. Steinberg, H. Bourne Third row: Poster session First row: W. Franke; F. Bonhoeffer, H.R. Horvitz; D. Kubler Second row: R. Akeson, L Sanes; D. Mynarcik, J. Whittaker Third row: H. Lodish; J. Brugge; R. Reed Fourth row: L. Lasky; C. Williams; J. Thorner, R. Hynes Foreword

The biochemical processes that occur at the cell surface have profound effects on the well-being of single cells and whole organisms. Cell surface phenomena are principal areas of study in all disciplines of modern biological research, including physiology, development and differentiation, immunology, cancer, neurobiology, and cell growth and death. Moreover, the molecules that lie on or immediately subjacent to the cell surface comprise prime targets for alleviation or treatment of human diseases. Because of the importance of this research, it was decided to focus the 57th Cold Spring Harbor Symposium on the topic of The Cell Surface. There was, however, a considerable challenge to bring together a diverse group of scientists who study biology at the cell surface, but there was also comfort in the fact that common molecular themes appear in all species, from bacteria to man. The very first Symposium, organized by Reginald Harris in 1933, was entitled Surface Phenomena, and in the intervening years, several other Symposia have dealt with many aspects of this broad topic. In 1992, given the breadth of the program, it was not possible to invite all the major scientists working in this field, and difficult decisions were necessary. In the organization of the meeting, I received enormous help and advice from Richard Hynes, a principal co-organizer, with additional help from Richard Axel and Cory Goodman. The meeting took place from May 27 to June 3, 1992. Following an introduction by Jim Watson, the first night speakers, Christiane Nfisslein-Volhard, Dan Koshland, Jr., Tony Hunter, and Gerald Edelman, provided a fascinating overview and a taste of things to come. Over the next six days, 324 participants witnessed a total of 82 oral presentations and 89 posters; the high standard set on the first night was maintained throughout the meeting. An insightful summary was presented by Mel Simon, who displayed an excellent grasp of all the science. Essential funds to hold such a meeting were provided by the National Science Foundation; the U.S. Department of Energy, Office of Health and Environmental Research; and the following divisions of the National Institutes of Health: the National Cancer Institute, the National Institute of Neurological Disorders and Stroke, and the National Institute on Aging. Additional funding came from our corporate sponsors, who provide increasingly vital funding: Akzo Pharma International B. V.; Alafi Capital Company; American Cyanamid Company; Amgen Inc.; Applied Biosystems, Inc.; BASF Bioresearch Corporation; Becton Dickinson and Company; Boehringer Mannheim Corporation; Ciba-Geigy Corporation/ Ciba-Geigy Limited; Diagnostic Products Corporation; The Du Pont Merck Pharmaceutical Company; Eastman Kodak Company; Genentech, Inc.; Glaxo; Hoffmann-La Roche Inc.; Johnson & Johnson; Kyowa Hakko Kogyo Co., Ltd.; Life Technologies, Inc.; Eli Lilly and Company; MetPath Inc.; Millipore Corporation; Monsanto Company; New England BioLabs, Inc.; Oncogene Science, Inc.; Pall Corporation; Perkin-Elmer Cetus Instruments; Pfizer Inc.; Recordati; Sandoz Research Institute; Schering-Plough Corporation; SmithKline Beecham Pharmaceuticals; Sumitomo Pharmaceuticals Co., Ltd.; Toyobo Co., Ltd.; The Upjohn Company; The Wellcome Research Laboratories, Burroughs Wellcome Co.; and Wyeth-Ayerst Research. I thank the industrious staff in our Meetings Office, particularly Barbara Ward, Diane Tighe, and Micki McBride, for handling all the registrations, mailings, and housing arrange- ments in an expert and efficient manner. Herb Parsons and his staff provided wonderful audiovisual assistance. I am particularly indebted to Barbara Weinkauff, who handled much of the correspondence and many telephone calls during the organization of the meeting. Finally, the unfailing efforts of the Publications office, particularly Patricia Barker, Dorothy Brown, Mary Cozza, Joan Ebert, and Inez Sialiano, all under the guidance of Nancy Ford, made publication of this volume possible.

Bruce Stillman

xvii Contents

Symposium Participants V Foreword xvii

Receptors

Receptors and Transmembrane Signaling B.L. Stoddard, H.-P. Biemann, and D.E. Koshland, Jr. 1 A Model for Transmembrane Signaling in a Bacterial Chemotaxis Receptor S.-H. Kim, G.G. Privd, J. Yeh, W.G. Scott, and M.V. Milburn 17 Receptor Protein Tyrosine Kinases and Phosphatases T. Hunter, R.A. Lindberg, D.S. Middlemas, S. Tracy, and P. van der Geer 25 The Trk Family of Tyrosine Kinases: Receptors for NGF-related Neurotrophins L.F. Parada, P. Tsoulfas, L. Tessarollo, J. Blair, S.W. Reid, and D. Soppet 43 Cloning and Analysis of Neurotrophic Factor Receptors Using Function-based Strategies D.J. Glass, D.R. Gies, T. Stitt, S. Davis, P. Hantzopoulos, N.Y. Ip, M. Goldfarb, and G.D. Yancopoulos 53 Interactions of PDGF and FGF Receptors with Cytoplasmic Signaling Mole- cules K.G. Peters, J.A. Escobedo, W.J. Fantl, and L.T. Williams 63 Role of SH2-containing Proteins in Cellular Signaling by Receptor Tyrosine Ki- nases J. Schlessinger, M. Mohammadi, B. Margolis, and A. Ullrich 67 Phosphatidylinositol-3 Kinase and Growth Regulation S.P. Soltoff, C.L. Carpenter, K.R. Auger, R. Kapeller, B. Schaffhausen, and L.C. Cantley 75 The Type II TGF-/3 Receptor Signals Diverse Responses in Cooperation with the Type I Receptor J.L. Wrana, J. Cfrcamo, L. Attisano, S. Cheifetz, A. Zentella, F. L6pez-Casillas, and J. Massagud 81 Protein Tyrosine Phosphatases: The Problems of a Growing Family N.K. Tonks, Q. Yang, A.J. Flint, M.F.B. G. Gebbink, B.R. Franza, Jr., D.E. Hill, H. Sun, and S. Brady-Kalnay. 87 The Erythropoietin Receptor: Dimerization, Activation, and Tumorigenesis H.F. Lodish, D. Hilton, G. Longmore, S.S. Watowich, and A. Yoshimura 95 Regulation of Protein Tyrosine Kinase Activation by the T-cell Antigen Receptor ~" Chain A. Weiss, A.C. Chan, M. Iwashima, D. Straus, and B.A. Irving 107 Activation of Immune System Effector Function by T-cell or Fc Receptor Intracellular Domains C. Romeo, W. Kolanus, M. Amiot, and B. Seed 117

G-Protein-coupled Receptors and Effectors

G-Protein-coupled Receptors: Regulatory Role of Receptor Kinases and Arrestin Proteins R.J. Lefkowitz, J. Inglese, W.J. Koch, J. Pitcher, H. Attramadal, and M. G. Caron 127 Regulation of Mammalian Adenylyl Cyclases by G-Protein a and/33' Subunits W.-J. Tang, J.A. I~iguez-Lluhi, S. Mumby, and A.G. Gilman 135 Detection of Coincident Signals by G Proteins and Adenylyl Cyclase H.R. Bourne, K.D. Lustig, Y.H. Wong, and B.R. Conklin 145 Thrombin Receptor Structure and Function S.R. Coughlin, R.M. Scarborough, T.-K.H. Vu, and D. T. Hung 149 Guanylyl Cyclases: Ligands and Functions T.D. Chrisman, S. Schulz, and D.L. Garbers 155 Lysophosphatidic Acid: A Novel Phospholipid with Hormone- and Growth Factor-like Activities W.H. Moolenaar, R.L. van der Bend, E.J. van Corven, K. Jalink, T. Eichholtz, and W J. van Blitterswijk 163 xix CONTENTS

G-Protein-linked Signaling Pathways Mediate Development in Dictyostelium R.L. Johnson, R. Gundersen, D. Hereld, G.S. Pitt, S. Tugendreich, C.L. Saxe, A.R. Kimmel, and P.N. Devreotes 169 Molecular Genetic Analysis of Signal Transduction Pathways Controlling Multicellular Development in Dictyostelium A.B. Cubitt, F. Carrel, S. Dharmawardhane, C. Gaskins, J. Hadwiger, P. Howard, S. K. O. Mann, K. Okaichi, K. Zhou, and R. A. Firth 177

Adhesion Receptors

Signaling between the Extracellular Matrix and the Cytoskeleton: Tyrosine Phosphor- ylation and Focal Adhesion Assembly L.H. Romer, K. Burridge, and C.E. Turner 193 Mechanisms of Fibronectin and Integrin Function during Cell Adhesion and Migra- tion K.M. Yamada, S. Aota, S.K. Akiyama, and S.E. LaFlamme 203 Functional Roles for Integrin a Subunit Cytoplasmic Domains M.E. Hemler, P.D. Kassner, and B. M. C. Chan 213 Ligand Binding to Integrins: Dynamic Regulation and Common Mechanisms M.H. Ginsberg, T.E. O' Toole, J.C. Loftus, and E.F. Plow 221 Role of a v Integrins and Vitronectin in Human Melanoma Cell Growth L.C. Sanders, B. Felding-Habermann, B.M. Mueller, and D.A. Cheresh 233 Genetic Interactions with Integrins during Wing Morphogenesis in Drosophila L.H.V. Wessendorf, M. Wehrli, A. DiAntonio, and M. Wilcox 241 Toward a Genetic Analysis of Cell-Matrix Adhesion R.O. Hynes, E.L. George, E.N. Georges, J.-L. Guan, H. Rayburn, and J. T. Yang 249 Glycosylation-dependent Cell Adhesion Molecule 1: A Novel Mucin-like Adhesion Ligand for L-Selectin L.A. Lasky, M.S. Singer, D. Dowbenko, Y.Imai, W. Henzel, C. Fennie, S. Watson, and S.D. Rosen 259 Quantitative Determination of Selectin-Carbohydrate Interactions R.M. Nelson, A. Aruffo, S. Dotich, O. Cecconi, G. Mannori, and M.P. Bevilacqua 271 Molecular Mechanisms of Complex Carbohydrate Recognition at the Cell Sur- face W.I. Weis, M.S. Quesenberry, M.E. Taylor, K. Bezougka, W.A. Hendrick- son, and K. Drickamer 281 Lymphocyte Homing Receptors M.C.-T. Hu, M.H. Siegelman, B. Holzmann, D.T. Crowe, and I.L. Weissman 291 Extracellular Matrix/Growth Factor Interactions E. Ruoslahti, Y. Yamaguchi, A. Hildebrand, and W.A. Border 309 Mediation and Inhibition of Cell Adhesion by Morphoregulatory Molecules G.M. Edelman 317 Cytoplasmic Control of Cadherin-mediated Cell-Cell Adhesion M. Takeichi, S. Hirano, N. Matsuyoshi, and T. Fujimori 327 Cadherins and the Morphogenesis of Epithelial Tissues in Xenopus Embryos C. Kintner 335 DCC: A Tumor Suppressor Gene Expressed on the Cell Surface L. Hedrick, K.R. Cho, J. Boyd, J. Risinger, and B. Vogelstein 345

Development

Intercellular Signaling during Caenorhabditis elegans Vulval Induction P.W. Sternberg, R.J. Hill, G. Jongeward, L.S. Huang, and L. Carta 353 Genes Involved in Two Caenorhabditis elegans Cell-signaling Pathways S.G. Clark, M.J. Stern, and H.R. Horvitz 363 Signal Transduction Pathway Initiated by Activation of the sevenless Tyrosine Kinase Receptor M.A. Simon, R.W. Carthew, M.E. Fortini, U. Gaul, G. Mardon, and G.M. Rubin 375 Induction of the R7 Neuron in the Drosophila Compound Eye: The bride of sevenless and sevenless Interaction S.L. Zipursky, H. Kriimer, R. Cagan, A. Hart, and D. Van Vactor, Jr. 381 CONTENTS ~i

Delta, Notch, and shaggy." Elements of a Lateral Signaling Pathway in Drosophila P. Simpson, M. Bourouis, P. Heitzler, L. Ruel, M. Haenlin, and P. Ramain 391 Regulation of Induction by GLP1, a Localized Cell Surface Receptor in Caenorhabditis elegans J. Kimble, S. Crittenden, E. Lambie, V. Kodoyianni, S. Mango, and E. Troemel 401 Extracellular Morphogens in Drosophila Embryonic Dorsal-Ventral Patterning K.V. Anderson, D.S. Schneider, D. Morisato, Y. Jin, and E.L. Ferguson 409

Neurobiology

Adhesive Interactions That Regulate Development of the Retina and Primary Visual Projection L.F. Reichardt, B. Bossy, L de Curtis, K.M. Neugebauer, K. Venstrom, and D. Sretavan 419 Second Messengers Underlying Cell-contact-dependent Axonal Growth Stimulated by Transfected N-CAM, N-cadherin, or L1 F.S. Walsh and P. Doherty 431 Development of Neuromuscular Specificity in Drosophila A. Nose, D. Van Vactor, V. Auld, and C.S. Goodman 441 Rostrocaudal Differences among Muscles Revealed by a Transgene: Graded Expres- sion at Low Copy Number J.R. Sanes, M.J. Donoghue, M. C. Wallace, and J. P. Merlie 451 Agrin: A Synaptic Basal Lamina Protein That Regulates Development of the Neuro- muscular Junction J.T. Campanelli, M. Ferns, W. Hoch, F. Rupp, M. yon Zastrow, Z. Hall, and R.H. Scheller 461 Control of Floor Plate Identity and Function in the Embryonic Nervous System A. Klar, T.M. Jessell, and A. Ruiz i Altaba 473 Neurexins M. Geppert, Y.A. Ushkaryov, Y. Hata, B. Davletov, A. G. Petrenko, and T. C. Siidhof 483 Elucidation of Biophysical and Biological Properties of Voltage-gated Potassium Chan- nels T.J. Baldwin, E. Isacoff, M. Li, G.A. Lopez, M. Sheng, M.L. Tsaur, Y.N. Jan, and L.Y. Jan 491 Mechanisms of Sensitivity and Specificity in Olfaction R.R. Reed 501 Molecular Biology of Smell: Expression of the Multigene Family Encoding Putative Odorant Receptors A. Chess, L. Buck, M.M. Dowling, R. Axel, and J. Ngai 505 Pharmacological and Genetic Approaches to the Analysis of Tyrosine Kinase Function in Long-term Potentiation T.J. O'Dell, S. G.N. Grant, K. Karl, P.M. Soriano, and E.R. Kandel 517 a Calcium/Calmodulin Kinase II Mutant Mice: Deficient Long-term Potentiation and Impaired Spatial Learning A.J. Silva, Y. Wang, R. Paylor, J.M. Wehner, C.F. Stevens, and S. Tonegawa 527 Structure and Interactions of CD4 S. C. Harrison, J. Wang, Y. Yan, T. Garrett, J. Liu, U. Moebius, and E. Reinherz 541 Structural Aspects of CD4 and CD8 Involvement in the Cellular Immune Re- sponse W A. Hendrickson, P.D. Kwong, D.J. Leahy, S.-E. Ryu, H. Yamaguchi, S. Fleury, and R.-P. SOkaly 549 Biochemical Anatomy of Antigen Processing C.A. Nelson, C.V. Harding, and E.R. Unanue 557 MHC Products: Biosynthesis, Intracellular Traffic, and "Empty" Molecules H.L. Ploegh 565 Transport and Expression of Class I MHC Glycoproteins in an Antigen-processing Mutant Cell Line E.-M. Click, K.S. Anderson, M.J. Androlewicz, M.L. Wei, and P. Cresswell 571 Dedicated Transporters for Peptide Export and Intercompartmental Traffic in the Yeast Saccharomyces cerevisiae K. Kuchler, H.M. G6ransson, M.N. Viswanathan, and J. Thorner 579

Membrane Traffic and Cytoskeletal Assembly

Each Caveola Contains Multiple Glycosyl-phosphatidylinositol-anchored Membrane Proteins Y.-S. Ying, R. G.W. Anderson, and K.G. Rothberg 593 xxii CONTENTS

Molecular Flypaper, Atherosclerosis, and Host Defense: Structure and Function of the Macrophage Scavenger Receptor M. Krieger, J.M. Abrams, A. Lux, and H. Steller 605 Biogenesis of Cell-surface Polarity in Epithelial Cells and Neurons K. Simons, P. Dupree, K. Fiedler, L.A. Huber, T. Kobayashi, T. Kurzchalia, V. Olkkonen, S. Pimplikar, R. Parton, and C. Dotti 611 Regulation of Epithelial Cell Polarity: A View from the Cell Surface W.J. Nelson, R. Wilson, D. Wollner, R. Mays, H. McNeill, and K. Siemers 621 Cytoplasmic Control of Cell Adhesion B. Geiger, 0. Ayalon, D. Ginsberg, T. Vol- berg, J.L. Rodriguez Fern~ndez, Y. Yarden, and A. Ben-Ze'ev 631 Desmosomal Proteins: Mediators of Intercellular Coupling and Intermediate Filament Anchorage W..W.. Franke, S.M. Troyanovsky, P.J. Koch, R. Troyanovsky, B. Fouquet, and R.E. Leube 643 Role of the Zygotic Genome in the Restructuring of the Actin Cytoskeleton at the Cycle-14 Transition during Drosophila Embryogenesis E.D. Schejter, L.S. Rose, M.A. Postner, and E. Wieschaus 653 Distinct Patterns of Actin Organization Regulated by the Small GTP-binding Proteins Rac and Rho A.J. Ridley and A. Hall 661 Summary: The Cell Surface Regulates Information Flow, Material Transport, and Cell Identity M.I. Simon 673

Author Index 689

Subject Index 691