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Dominique Bagnard, Ph.D.
Nervous System to
Tumor Biology
Neuropilin: From Nervous System to Vascular and Tumor Biology
Neuropilin:
From Nervous System to Vascular and Tumor Biology
Edited by
Dominique Bagnard, Ph.D.
Maître de Conférences Université Louis Pasteur 67084 Strasbourg, France
email: bagnard@neurochem.u-strasbg.fr
KluwerAcademic / Plenum Publishers New York, Boston, Dordrecht, London, Moscow
Library of Congress Cataloging-in-Publication Data
CIP applied for but not received at time of publication.
Neuropilin: From Nervous System to Vascular and Tumor Biology Edited by Dominique Bagnard
ISBN 0-306-47416-6 AEMB volume number: 515
©2002 Kluwer Academic / Plenum Publishers and Landes Bioscience
Kluwer Academic / Plenum Publishers 233 Spring Street, New York, NY 10013 http://www.wkap.nl
Landes Bioscience
810 S. Church Street, Georgetown, TX 78626 http://www.landesbioscience.com; http://www.eurekah.com Landes tracking number: 1-58706-168-6
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A C.I.P. record for this book is available from the Library of Congress.
All rights reserved.
No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher.
Printed in the United States of America.
PREFACE
Cell adhesion is one of the most important properties controlling embryonic development. Extremely precise cell-cell contacts are established according to the nature of adhesion molecules that are expressed on the cell surface. The identifica-tion of several families of adhesion molecules, well conserved throughout evolu-tion, has been the basis of a considerable amount of work over the past 20 years that contributed to establish functions of cell adhesion in almost all organs. Nowadays, cell adhesion molecules are not just considered as cellular glue but are thought to play critical roles in cell signaling. Their ability to influence cell proliferation, mi-gration, or differentiation depends on both cell surface adhesion properties and acti-vation of intracellular pathways. The next challenge will be to understand how these molecules interact with each other to ensure specific functions in the morphogen-esis of very sophisticated systems. Indeed, by exploring the cellular and molecular mechanisms of nervous system development, the group of H. Fujisawa in Japan identified in 1987 an adhesion molecule, neuropilin, highly expressed in the neuro-pile of amphibian optic tectum. Ten years later, two groups discovered that neuropilin is a receptor for guidance signals of the semaphorin family. Axon guidance is a critical step during brain development and the mechanisms ensuring growth cone navigation are beginning to be well understood. The semaphorins are bifunctional signals defining permissive or inhibitory pathways sensed by the growth cone. Moreover, a semaphorin can be repellent or attractive depending on the axonal popu-lations. The complexity of the signaling cascade triggered by the semaphorin is further illustrated by the capacity of Sema3A to be repulsive for the axon and attrac-tive for the dendrites of cortical neurons. Hence, an appropriate response of the growth cone requires the recruitment of a receptor complex enabling the integration of this varying information. The analysis of the structure of neuropilin revealed a very short intracellular domain lacking transduction capacities. Because of these works, several groups started to analyze the possible interactions of neuropilin and described various binding partners allowing semaphorin transduction. The current view considers neuropilin as the heart of a receptor complex consisting of multiple transmembrane molecules including tyrosine kinase receptors or other adhesion molecules. In front of the growing implication of neuropilin during various physi-ologic and pathophysiologic processes, we decided to edit this comprehensive book designed to illustrate the diverse functions of this basic adhesion molecule. The first part of the volume contains four Chapters presenting the discovery of neuropilin and demonstrating its principal functions in the nervous, vascular and immune sys-tems. In the second part, four Chapters describe the molecular structure of neuropilin and dissect the mechanisms ensuring receptor complex formation with various mol-
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