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Ciba Foundation Symposium 179 - The Molecular Basis of Smell and Taste Transduction PDF

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THE MOLECULAR BASIS OF SMELL AND TASTE TRANSDUCTION , The Ciba Foundation is an international scientific and educational charity (Registered Charity No. 313574). 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 W1 N 48N, provides facilities for meetings of all kinds. Its Media Resource Service supplies information to journalists on all scientific and technological topics. The library, open five 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 SvmDosium 179 THE MOLECULAR BASIS OF SMELL AND TASTE TRANSDUCTION A Wiley-lnterscience Publication 1993 JOHN WILEY & SONS Chichester . New York . Brisbane . Toronto . Singapore OCiba Foundation 1993 Published in 1993 by John Wiley & Sons Ltd Baffins Lane, Chichester West Sussex PO19 lUD, England All rights reserved. No part of this book may be reproduced by any means, or transmitted, or translated into a machine language without the written permission of the publisher. Other Wiley Editorial Offices John Wiley & Sons, Inc., 605 Third Avenue, New York, NY 10158-0012, USA Jacaranda Wiley Ltd, G.P.O. Box 859, Brisbane, Queensland 4001, Australia John Wiley & Sons (Canada) Ltd, 22 Worcester Road, Rexdale, Ontario M9W 1L1, Canada John Wiley & Sons (SEA) Pte Ltd, 37 Jalan Pemimpin #05-04, Block B, Union Industrial Building, Singapore 2057 Suggested series entry for library catalogues: Ciba Foundation Symposia Ciba Foundation Symposium 179 ix+287 pages, 58 figures, 9 tables Library of Congress Cataloging-in-Publication Data The Molecular basis of smell and taste transduction / Derek Chadwick, Joan Marsh, Jamie Goode, editors. p. cm.-(Ciba Foundation symposium; 179) Symposium on the Molecular Basis of Smell and Taste Transduction, held at the Ciba Foundation, London, Feb. 1993. Includes bibliographical references and index. ISBN 0-47 1-93946-3 1. Smell-Molecular aspects-Congresses. 2. Taste-Molecular aspects-Congresses. 3. Cellular signal transduction-Congresses. 4. Second messengers (Biochemistry)-Congresses. 5. G proteins- Congresses. I. Chadwick, Derek. 11. Marsh, Joan. 111. Goode, Jamie. 1V. Symposium on the Molecular Basis of Smell and Taste Transduction (1993 :London, Eng.) V. Series. QP458.M63 1993 591.1 ' 826-dc20 93-28783 CIP British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library ISBN 0 471 93946 3 Phototypeset by Dobbie Typesetting Limited, Tavistock, Devon Printed and bound in Great Britain by Biddles Ltd, Guildford. Contents Symposium on the molecular basis of smell and taste transduction, held at the Ciba Foundation, London 19-21 February 1993 Editors: Derek Chadwick, Joan Marsh (Organizers) and Jamie Goode This symposium is based on a proposal made by Frank Margolis and Tom Getchell F. L. Margolis Introduction 1 F. L. Margolis, K. Kudrycki, C. Stein-Izsak, M. Grillo and R. Akeson From genotype to olfactory neuron phenotype: the role of the Olf-l-binding site 3 Discussion 20 T. V. Getchell, Z. Su and M. L. Getchell Mucous domains: microchemical heterogeneity in the mucociliary complex of the olfactory epithelium 27 Discussion 40 L. B. Buck Receptor diversity and spatial patterning in the mammalian olfactory system 51 Discussion 64 M. M. Wang and R. R. Reed Molecular mechanisms of olfactory neuronal gene regulation 68 Discussion 13 M. R. Lerner, M. N. Potenza, G. F. Graminski, T. McClintock, C. K. Jayawickreme and S. Kame A new tool for investigating G protein-coupled receptors 76 Discussion 84 General discussion I 88 H. Breer Second messenger signalling in olfaction 97 Discussion 109 V vi Contents S. Firestein and F. Zufall Membrane currents and mechanisms of olfactory transduction 115 Discussion 126 D. Lancet, N. Ben-Arie, S. Cohen, U. Gat, R. Gross-Isseroff, S. Horn-Saban, M. Khen, H. Lehrach, M. Natochin, M. North, E. Seidemann and N. Walker Olfactory receptors: transduction, diversity, human psychophysics and genome analysis 131 Discussion 14 1 General Discussion I1 147 J. Carlson Molecular genetics of Drosophila olfaction 150 Discussion 162 H. Schmale, C. Ahlers, M. Blaker, K. Kock and A. I. Spielman Perireceptor events in taste 167 Discussion 180 S. K. McLaughlin, P. J. McKinnon, A. Robichon, N. Spickofsky and R. F. Margolskee Gustducin and transducin: a tale of two G proteins 186 Discussion 196 S. C. Kinnamon Role of apical ion channels in sour taste transduction 201 Discussion 2 10 J. A. DeSimone, Q. Ye and G. E. Heck Ion pathways in the taste bud and their significance for transduction 218 Discussion 229 P. Sengupta, H. A. Colbert, B. E. Kimmel, N. Dwyer and C. I. Bargmann The cellular and genetic basis of olfactory responses in Caenorhabditis e[egans 235 Discussion 244 L. M. Bartoshuk Genetic and pathological taste variation: what can we learn from animal models and human disease? 251 Discussion 262 General discussion 111 268 F. L. Margolis Summing-up 274 Index of contributors 277 Subject index 279 Participants B. W. Ache University of Florida, Whitney Laboratory, 9505 Ocean Shore Boulevard, St Augustine, FL 32086, USA C. I. Bargmann Program in Developmental Biology, University of California, Medical School, 5 13 Parnassus Avenue, San Francisco, CA 94143-0452, USA L. M. Bartoshuk Department of Surgery, Yale University School of Medicine, 333 Cedar Street, PO Box 208041, New Haven, CT 06520-8041, USA H. Breer Institut fur Zoophysiologie, Universitat Hohenheim (230), Postfach 70 05 62, D-7000 Stuttgart 70, Germany L. Buck Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 021 15, USA J. Caprio Department of Zoology and Physiology, Louisiana State University, Baton Rouge, LA 70803, USA J. Carlson Department of Biology, Yale University, Kline Biology Tower, PO Box 6666, New Haven, CT 0651 1-81 12, USA J. A. DeSimone Department of Physiology, Box 55 1, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0551, USA E. E. Fesenko Institute of Cell Biophysics, Academy of Sciences, 142292 Pushchino, Moscow Region, Russia S. Firestein Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, PO Box 208041, New Haven, CT 06520-8041, USA T. V. Getchell Chandler Medical Centre, University of Kentucky, College of Medicine, 800 Rose Street, Lexington, KY 40536-0084, USA vii viii Participants H. Hatt Physiologisches Institut, Technische Universitat Miinchen, Biedersteiner Strasse 29, D-8000 Miinchen 40, Germany P. M. Hwang (Bursar) Department of Neuroscience, The Johns Hopkins University, School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA S. C. Kinnamon Department of Anatomy and Neurobiology, Colorado State University, Fort Collins, CO 80523, USA T. Kurahashi Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104-3308, USA D. Lancet Department of Membrane Research and Biophysics, The Weizmann Institute of Science, 76100 Rehovot, Israel M. Lerner Howard Hughes Medical Institute, Yale University School of Medicine, BCMM 254, PO Box 9812, New Haven, CT 06536-0812, USA B. Lindemann Physiologisches Institut, Universitat des Saarlandes, D-6650 Homburg, Germany 1. Lush Department of Genetics and Biometry, University College London, Wolfson House, 4 Stephenson Way, London NWl 2HE, UK F. L. Margolis (Chairman) Laboratory of Chemosensory Neurobiology, Roche Institute of Molecular Biology, Roche Research Center, 340 Kingsland Street, Nutley, NJ 071 10-11 99, USA R. F. Margolskee Roche Institute of Molecular Biology, Roche Research Center, 340 Kingsland Street, Nutley, NJ 071 10-1 199, USA P. Pelosi Istituto di Industrie Agrarie, Universita di Pisa, Via S Michele degli Scalzi 4, 1-56100 Pisa, Italy R. R. Reed Department of Molecular Biology and Genetics, The Johns Hopkins University, School of Medicine, Howard Hughes Medical Institute, 725 North Wolfe Street, Baltimore, MD 21205, USA G. V. Ronnett Department of Neuroscience, The Johns Hopkins University, School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA H. Schmale Institut fur Zellbiochemie und klinische Neurobiologie, Universitat Hamburg, Martinistrasse 52, D-20246 Hamburg, Germany Participants iX 0. Siddiqi Molecular Biology Unit, Tata Institute of Fundamental Research, Homi Bhabha Road, Bombay 400 005, India J. H. Teeter Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104-3308, USA J. Van Houten Department of Zoology, Marsh Life Science Building, University of Vermont, Burlington, VT 05405-0086, USA Novartis Foundation Symposium Edited by Derek Chadwick, Joan Marsh, Jamie Goode Copyright 0 1993 by Ciba Foundation lntroduc tion Frank L. Margolis Laboratory of Chemosensory Neurobiology, Roche Institute of Molecular Biology, 340 Kingsland Street, Nutley, NJ 071 10-1 199, USA I would like to start by reviewing the origins of this symposium and indicating some of the broad questions that we hope to answer. Two years ago I was in this room as a discussant at a meeting that was held on the regeneration of sensory cells. The one thing, apart from the science, that I came away with at the end of the meeting was the realization that it was essential that I find some way to come back! After discussions with my friend and collaborator, Tom Getchell, we decided to try and put together an equivalent meeting on the chemical senses, to create a period of intense interaction that would serve as an opportunity to identify the state of the field and the next set of questions to be addressed. So we drafted a proposal which we presented to the Ciba Foundation, resulting in this meeting. This is actually the second Ciba Foundation symposium on the chemical senses. The first, held nearly a quarter of a century ago in 1969, was called Taste and Smell in Vertebrates (Ciba Foundation 1970). I would like to quote from Professor Otto Lowenstein’s introduction, where he said ‘we have now arrived at the point where what are sometimes considered to be the Cinderellas of the senses, taste and smell, are to be discussed. You may know only too well how anyone teaching sensory physiology usually enjoys himself until he comes to taste and smell, and then he tends to run out of teachable material. But I have a feeling that we are nearing a breakthrough in this field, and therefore it is very timely that we have this symposium now.’ Finally, nearly 25 years later, we have reached the point where we are seeing the breakthrough predicted by Professor Lowenstein in 1969. Over the last few years, the contemporary techniques of molecular biology and patch-clamp recording have led to major advances. Consequently, we now know a great deal about the mechanisms, molecules and interactions involved in chemosensory transduction. As this meeting proceeds over the next few days, I think we will see how true this is. I want to state what I believe the questions are that we are going to try to answer or, at least, discuss in this symposium. One of the things that became apparent to me in rereading the proposal that Tom Getchell and I had written was that several of the issues we raised as open questions two years ago have already been at least partly answered. Nevertheless, there are several questions that I hope we will address over the next few days: 1

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