CARBOHYDRATE RECOGNITION IN CELLULAR FUNCTION The Ciba Foundation is an international scientific and educational charity. It was established in 1947 by the Swiss chemical and pharmaceutical company of ClBA Limited-now CIBA-GEIGY Limited. The Foundation operates independently in London under English trust law. The Ciba Foundation exists to promote international cooperation in biological, medical and chemical research. It organizes about eight international multidisciplinary symposia each year on topics that seem ready for discussion by a small group of research workers. The papers and discussions are published in the Ciba Foundation symposium series. The Foundation also holds many shorter meetings (not published), organized by the Foundation itself or by outside scientific organizations. The staff always welcome suggestions for future meetings. The Foundation’s house at 41 Portland Place, London WIN 4BN, provides facilities for meetings of all kinds. Its Media Resource Service supplies information to journalists on all scientific and technological topics. The library, open seven days a week to any graduate in science or medicine, also provides information on scientific meetings throughout the world and answers general enquiries on biomedical and chemical subjects. Scientists from any part of the world may stay in the house during working visits to London. Ciba Foundation Symposium 145 CARBOHYDRATE RECOGNITION IN CELLULAR FUNCTION A Wiley-lnterscience Publication 1989 JOHN WILEY & SONS Chichester New York . Brisbane Toronto . Singapore OCiba Foundation 1989 Published in 1989 by John Wiley & Sons Ltd, Chichester, UK. Suggested series entry for library catalogues: Ciba Foundation Symposia Ciba Foundation Symposium 145 x +294 pages, 69 figures, 24 tables Library of Congress Cataloging-in-Publication Data Carbohydrate recognition in cellular function. p. cm.-(Ciba Foundation symposium ; 145) ‘Symposium on Carbohydrate Recognition in Cellular Function, held at the Ciba Foundation, London, 15-17 November 1988.’ ‘Editors: Gregory Bock (organizer) and Sara Harnett.’ ‘A Wiley-Interscience publication.’ Bibliography: p. Includes index. ISBN 0 471 92307 9 1. Cell receptors-Congresses. 2. Carbohydrates-Congresses. 3. Cellular recognition-Congresses. I. Bock, Gregory. 11. Harnett, Sara. 111. Symposium on Carbohydrate Recognition in Cellular Function (1988: Ciba Foundation) IV. Series. QH603.C43C37 1989 574.87’6-dc20 89-9153 CIP British Library Cataloguing in Publication Data Carbohydrate recognition in cellular function. 1. Mammals. Carbohydrates. Metabolism I. Series 599.01 ’924 ISBN 0 471 92307 9 Phototypeset by Dobbie Typesetting Limited, Devon. Printed and bound in Great Britain by Bath Press, Bath, Avon. Contents Symposium on Carbohydrate Recognition in Cellular Function, held at the Ciba Foundation, London, 15-1 7 November 1988 The topic for this symposium was proposed by Dr T. Feizi Editors: Gregory Bock (Organizer) and Sara Harnett E. Ruoslahti Introduction 1 J. P. Carver, S. W. Michnick, A. Imberty and D. A. Cumming Oligosaccharide-protein interactions: a three-dimensional view 6 Discussion 18 M. P. Czech, R. E. Lewis and S. Corvera Multifunctional glycoprotein receptors for insulin and the insulin-like growth factors 27 Discussion 42 K. Drickamer Multiple subfamilies of carbohydrate recognition domains in animal lectins 45 Discussion 58 T. Feizi Glycoprotein oligosaccharides as recognition structures 62 Discussion 74 Y. C. Lee Binding modes of mammalian hepatic Gal/GalNAc receptors 80 Discussion 93 General discussion I Two human lysosomal membrane glycoproteins 96 G. W. Hart, R. S. Haltiwanger, G. D. Holt and W. G. Kelly Nucleoplasmic and cytoplasmic glycoproteins 102 Discussion 11 2 Y. Nagai and S. Tsuji Bioactive ganglioside-mediated carbohydrate recognition in coupling with ecto-protein phosphorylation 1 19 Discussion 130 V VI Contents P. M. Wassarman Role of carbohydrates in receptor-mediated fertilization in mammals 135 Discussion 149 M. Schachner Families of neural adhesion molecules 156 Discussion 169 J. Finne Structural and biological properties of the carbohydrate units of nervous tissue glycoproteins 173 Discussion 183 M. A. Hynes, L. B. Buck, M. Gitt, S. Barondes, J. Dodd and T. M. Jessell Carbohydrate recognition in neuronal development: structure and expression of surface oligosaccharides and 0-galactoside-binding lectins 189 Discussion 2 10 General discussion I1 Expression c;f developmentally regulated carbo- hydrates 219 A. Kohata, T. Mizuochi, T. Endo and K. Furukawa Function and pathology of the sugar chains of human immunoglobulin G 224 Discussion 235 T. W. Rademacher and R. A. Dwek The role of oligosaccharides in modifying protein function 241 Discussion 255 M. Fukuda Leukosialin, a major sialoglycoprotein defining leucocyte differentiation 257 Discussion 268 Final general discussion The diversity of N-linked oligosaccharides on human immunodeficiency virus 277 E. Ruoslahti Chairman’s summing-up 283 Index of contributors 284 Subject index 286 Participants S. Barondes Department of Psychiatry, University of California, San Francisco, CA 94143, USA J. Carver Department of Medical Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8 M. P. Czech Department of Biochemistry, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, MA 01605, USA K. Drickamer Department of Biochemistry & Molecular Biophysics, Columbia University, 630 W 168th Street, New York, NY 10032, USA B. Ernst CIBA-GEIGY AG, CH-4002 Basle, Switzerland T. Feizi Section of Glycoconjugate Research, MRC Clinical Research Centre, Watford Road, Harrow, Middlesex HA1 3UJ, UK J. Finne Department of Medical Biochemistry, University of Turku, Kiinamyllynkatu 10, SF-20520 Turku, Finland M. Fukuda Carbohydrate Chemistry, La Jolla Cancer Research Foundation, Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA C. Gahmberg La Jolla Cancer Research Foundation, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA G. W. Hart Department of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205. USA 0. Hindsgaul Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2 viii Participants R. C. Hughes MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 IAA, UK T. M. Jessell Center for Neurobiology & Behavior, Howard Hughes Medical Institute, College of Physicians & Surgeons, Columbia University, 722 West 168th Street, PI Research Annex, 6th Floor, NY 10032, USA A. Kobata Department of Biochemistry, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan Y. C. Lee Department of Biology & McCollum-Pratt Institute, The Johns Hopkins University, 34th & Charles Streets, Baltimore, MD 21218, USA U. Lindahl Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences, The Biomedical Center, Box 575, S-75 123 Uppsala, Sweden T. Muramatsu Department of Biochemistry, Kagoshima University School of Medicine, 1208-1 Usuki-cho, Kagoshima 890, Japan Y. Nagai Department of Biochemistry, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113, Japan T. W. Rademacher Oxford Glycobiology Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK E. Ruoslahti (Chairman) La Jolla Cancer Research Foundation, Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA M. Schachner Department of Neurobiology, University of Heidelberg, Im Neuenheimer Feld 364, D-6900 Heidelberg 1, Federal Republic of Germany N. Sharon Department of Biophysics, The Weizmann Institute of Science, PO Box 26, 76100 Rehovot, Israel P. Stanley Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA J. E. Thomas-Oates (Ciba Foundation Bursar) Department of Biochemistry, Imperial College of Science & Technology, Exhibition Road, London SW7 2AZ, UK Participants ix J. Wang Department of Biochemistry, Michigan State University, East Lansing, MI 48824-1319, USA P. M. Wassarman Department of Cell & Developmental Biology, Roche Institute of Molecular Biology, Nutley, NJ 071 10, USA W. M. Watkins Division of Immunochemical Genetics, MRC Clinical Research Centre, Watford Road, Harrow, Middlesex HA1 3UJ, UK Novartis Foundation Symposium Edited by GregoIy Bock, Sara Hamett Copyright 0 1989 by Ciba Foundation lntroductio n E. Ruoslahti La Jolla Cancer Research Foundation, Cancer Research Center, 1090 1 North Torrey Pines Road, La Jolla, CA 92037, USA The role of carbohydrate recognition in cellular function is poorly understood. The functions of DNA and proteins (DNA, of course, being a substituted carbohydrate) are generally known. It is much less clear what carbohydrates do. A number of functions have been proposed and it is possible that they all are correct, but they have not been clearly defined. When we ask what carbohydrates do, some standard replies are that bacteria bind to them, that they are immunogenic, and that they glue clams to the hulls of boats. We need a more precise answer; carbohydrates clearly do not exist to help bacteria gain entrance to the body. In this field the study of molecular structure has progressed more rapidly than the understanding of function. I am sure we should all like to see that corrected. Nevertheless, the structural studies have been very interesting, starting with the classic work of Dr Winifred Watkins, whom we are pleased to have with us at this meeting, and progressing to some recent surprises with fascinating functional implications, such as the nuclear and cytoplasmic glycosylation. A persuasive argument used by those who defend the functionality of carbohydrates is that they must be important because there is a tremendous variation to their structure. However, we do not fully understand the basis of that variation. It is likely to be important, but in what way? I find it puzzling that there seems to be no species conservation for the expression of a given carbohydrate group in a given place. There are some very specific, developmentally regulated expression patterns for certain carbohydrate structures, but they do not seem to be conserved from species to species. It is possible that a particular carbohydrate structure may be important only in one or very few places. Then it may be simply coincidentally expressed at many other places. This is going to be difficult to sort out. In this sense, carbohydrate expression may be similar to the alternative splicing of mRNA; there may be only one protein where alternative splicing is important to a given cell, and many 1989 Carbohydrate recognition in cellular function. Wiley, Chichester (Ciba Foundation Symposium 145) p 1-5 1