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Structure and Function of the Neural Cell Adhesion Molecule NCAM
ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
Editorial Board:
NATHAN BACK, State University of New York at Buffalo
IruN r. CoHEN, The Weizmann Institute of Science
ABEL LAJTHA, N. S. Kline Institute for Psychiatric Research
JoHN D. LAMBrIS, University of Pennsylvania
roDoLFo PAoLETTI, University of Milan
For other titles published in the series, go towww.springer.com/series/5584
Vladimir BerezinEditor
Structure and Function of the Neural Cell Adhesion Molecule NCAM
EditorVladimir BerezinDepartment of Neuroscience and PharmacologyPanum Instituteuniversity of CopenhagenCopenhagen N, Denmark [email protected]
ISBN 978-1-4419-1169-8 e-ISBN 978-1-4419-1170-4DoI 10.1007/978-1-4419-1170-4Springer New York Dordrecht Heidelberg London
Library of Congress Control Number: 2009942988
© Springer Science+Business Media, LLC 2010All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, uSA), except for brief excerpts in connection with reviews or scholarly analysis. use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden.The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights.
Printed on acid-free paper
Springer is part of Springer Science+Business Media (www.springer.com)
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This book contains review articles that produce a snapshot of recent developments in the field of the neural cell adhesion molecule NCAM. The chapters are grouped into sections reflecting various aspects of NCAM structure and function. The themes cover the structural basis of cell adhesion mediated by NCAM and NCAM interaction partners, NCAM-mediated signaling determinants of NCAM function under physiological conditions and in disease, and the therapeutic potential of NCAM mimetics.
Section 1, “Structure and Ligands of NCAM,” introduces the reader to the struc-tural basis of NCAM-mediated cell adhesion, discussing the current knowledge of extracellular and intracellular NCAM ligands and the structural basis of NCAM inter-actions with the fibroblast growth factor (FGF) receptor. Section 2, “NCAM and Polysialic Acid,” focuses on NCAM polysialylation, discussing the structural and functional aspects of the most important posttranslational modifications of NCAM by the addition of a long linear homopolymer of sialic acid to the fifth Ig-like NCAM module. Section 3, “NCAM-mediated Signal Transduction,” is devoted to signal
Preface
Dr. Elisabeth Bock (Photo Keenpress)
vi Preface
transduction mechanisms associated with NCAM-mediated adhesion, with a focus on signaling pathways involved in NCAM-mediated neurite outgrowth, the role of growth-associated proteins, signaling through lipid microdomains, and signaling crosstalk with the epidermal growth factor (EGF) receptor. Section 4, “NCAM Metabolism,” focuses on current knowledge about NCAM biosynthesis and the gen-eration and role of soluble NCAM. Section 5, “NCAM, Synapses, Emotions, and Memory,” describes the role of NCAM in spine dynamics, synaptogenesis, and learn-ing and memory. Section 6, “NCAM in Disease,” covers the role of NCAM in neu-ropsychiatric disorders, neurodegenerative disorders, and cancer. Section 7, “Pharmacology of NCAM: NCAM Mimetics,” reviews current achievements in the in vivo and in vitro pharmacology of small NCAM mimetic peptides. Section 8, “orthologs and Paralogs of NCAM,” discusses current knowledge about the structure and function of the NCAM ortholog Fasciclin II and the NCAM paralog NCAM2.
The concluding section is devoted to Professor Elisabeth Bock, to whom this book is dedicated. Prof. Bock in the early 1970s identified the neural cell adhesion molecule NCAM as brain specific protein D2 (published in Journal of Neurochemistry, 1974, vol. 23, pp. 879–880). She has dedicated her professional career to the characterization of this very important and intriguing molecule.
I would like to thank everyone who has contributed to this book by writing review articles on various aspects of NCAM structure and function, Kristine Immediato for her kind assistance in managing the manuscripts, and Michael Arends for his professional proofreading of a number of the manuscripts. I would also like to acknowledge the European union-supported Integrated Project ProMEMorIA, which since 2005 has been a staunch supporter of NCAM-related research.
Denmark Vladimir Berezin
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Contents
Part I Structure and Ligands of NCAM
Structural Biology of NCAM ......................................................................... 3Vladislav Soroka, Christina Kasper, and Flemming M. Poulsen
Extracellular Protein Interactions Mediated by the Neural Cell Adhesion Molecule, NCAM: Heterophilic Interactions Between NCAM and Cell Adhesion Molecules, Extracellular Matrix Proteins, and Viruses ...................................................................................... 23Janne Nielsen, Nikolaj Kulahin, and Peter S. Walmod
Intracelluar Ligands of NCAM ..................................................................... 55Bettina Büttner and rüdiger Horstkorte
NCAM and the FGF-Receptor ...................................................................... 67Vladislav V. Kiselyov
The Role of ATP in the Regulation of NCAM Function .............................. 81Martin V. Hübschmann and Galina Skladchikova
Part II NCAM and Polysialic Acid
Polysialylation of NCAM ................................................................................ 95Herbert Hildebrandt, Martina Mühlenhoff, and rita Gerardy-Schahn
Structural Basis for the Polysialylation of the Neural Cell Adhesion Molecule .......................................................................................... 111Karen J. Colley
The Role of PSA-NCAM in Adult Neurogenesis .......................................... 127Eduardo Gascon, Laszlo Vutskits, and Jozsef Zoltan Kiss
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Use of PSA-NCAM in Repair of the Central Nervous System ................... 137Abderrahman El Maarouf and urs rutishauser
Part III NCAM-Mediated Signal Transduction
Signaling Pathways Involved in NCAM-Induced Neurite Outgrowth ....... 151Dorte Kornerup Ditlevsen and Kateryna Kolkova
Role of the Growth-Associated Protein GAP-43 in NCAM-Mediated Neurite Outgrowth .......................................................................................... 169Irina Korshunova and Mark Mosevitsky
The Neural Cell Adhesion Molecule NCAM and Lipid Rafts .................... 183Gro Klitgaard Povlsen and Dorte Kornerup Ditlevsen
The Neural Cell Adhesion Molecule and Epidermal Growth Factor Receptor: Signaling Crosstalk ........................................................... 199Gro Klitgaard Povlsen
Part IV NCAM Metabolism
Biosynthesis of NCAM .................................................................................... 213Kateryna Kolkova
Soluble NCAM ................................................................................................ 227Thomas Secher
Part V NCAM, Synapses, Emotions, and Memory
Role of NCAM in Spine Dynamics and Synaptogenesis .............................. 245D. Muller, P. Mendez, M. Deroo, P. Klauser, S. Steen, and L. Poglia
NCAM in Long-Term Potentiation and Learning ....................................... 257Barbara P. Hartz and Lars Christian B. rønn
Role of NCAM in Emotion and Learning ..................................................... 271Lisa Conboy, reto Bisaz, Kamila Markram, and Carmen Sandi
Part VI NCAM in Disease
NCAM in Neuropsychiatric and Neurodegenerative Disorders ................. 299Leann H. Brennaman and Patricia F. Maness
ixContents
Neural Cell Adhesion Molecule in Cancer: Expression and Mechanisms .............................................................................................. 319Silvia Zecchini and ugo Cavallaro
Part VII Pharmacology of NCAM: NCAM Mimetics
NCAM Mimetic Peptides: An Update ........................................................... 337Vladimir Berezin and Elisabeth Bock
Synthetic NCAM-Derived Ligands of the Fibroblast Growth Factor Receptor ............................................................................................... 355Stine Maria Hansen, Shizhong Li, Elisabeth Bock, and Vladimir Berezin
Dendritic Spine and Synapse Morphological Alterations Induced by a Neural Cell Adhesion Molecule Mimetic ............................... 373Michael Stewart, Victor Popov, Nikolai Medvedev, Paul Gabbott, Nicola Corbett, Igor Kraev, and Heather Davies
Part VIII Orthologs and Paralogs of NCAM
Fasciclin II: The NCAM Ortholog in Drosophila melanogaster ................. 387Lars V. Kristiansen and Michael Hortsch
The Neural Cell Adhesion Molecule NCAM2/OCAM/ RNCAM, a Close Relative to NCAM ............................................................ 403Nikolaj Kulahin and Peter S. Walmod
Part IX Conclusion
Honoring Dr. Elisabeth Bock ......................................................................... 423Vladimir Berezin
Index ................................................................................................................. 427
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Contributors
Vladimir BerezinProtein Laboratory, Department of Neuroscience and Pharmacology, Panum Institute, university of Copenhagen, 24.2, Blegdamsvej 3, DK-2200, Copenhagen N, Denmark [email protected]
Reto BisazLaboratory of Behavioral Genetics, Brain Mind Institute, EPFL, Lausanne, Switzerland
Elisabeth BockProtein Laboratory, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, university of Copenhagen, Blegdamsvej 3C, Building 6.2, Copenhagen, N, DK-2200, Denmark [email protected]
Leann H. BrennamanDepartment of Biochemistry and Biophysics, Silvio Conte Center for Schizophrenia research, university of North Carolina School of Medicine, Chapel Hill, NC 27599, uSA
Bettina BüttnerInstitut für Physiologische Chemie, Martin-Luther-universität Halle-Wittenberg, Hollystr.1, 06114 Halle, Germany
Ugo CavallaroIFoM, Via Adamello 16, I-20139 Milano, Italy [email protected]
Karen J. ColleyDepartment of Biochemistry and Molecular Genetics, university of Illinois College of Medicine, Chicago, IL, uSA [email protected]
xii Contributors
Lisa ConboyLaboratory of Behavioral Genetics, Brain and Mind Institute, EPFL, Swiss Federal Institute of Technology, CH-1015 Lausanne, Switzerland [email protected]
Nicola CorbettDepartment of Life Sciences, The open university, Milton Keynes, MK7 6AA, uK
Heather DaviesDepartment of Life Sciences, The open university, Milton Keynes, MK7 6AA, uK
M. De RooDepartment of Neuroscience, university of Geneva Medical Center, 1. M. Servet, 1211 Geneva 4, Switzerland
Dorte Kornerup DitlevsenProtein Laboratory, Institute of Neuroscience and Pharmacology, Panum Institute, university of Copenhagen, Building 6.2, Blegdamsvej 3, DK-2200 Copenhagen, DenmarkEnkam Pharmaceuticals A/S, Fruebjergvej 3 P.o. Box 58 2100 Copenhagen, Denmark [email protected]
Abderrahman El MaaroufMemorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, uSA [email protected]
Paul GabbottDepartment of Life Sciences, The open university, Milton Keynes, MK7 6AA, uK
Eduardo GasconDevelopmental Biology Institute of Marseilles-Luminy (IBDML), Case 907, Parc Scientifique de Luminy,13288 Marseille Cedex 9 France
Rita Gerardy-SchahnInstitute of Cellular Chemistry, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany [email protected]
Stine Maria HansenENKAM Pharmaceuticals A/S, Fruebjergvej 3, Copenhagen Ø, DK-2100, Denmark
Barbara P. HartzNeuroSearch A/S, Pederstrupvej 93, DK-2750 Ballerup, Denmark [email protected]
xiiiContributors
Herbert HildebrandtInstitute of Cellular Chemistry, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany
Rüdiger HorstkorteInstitut für Physiologische Chemie, Martin-Luther-universität Halle-Wittenberg, Hollystr.1, 06114 Halle, Germany [email protected]
Michael HortschDepartment of Cell and Developmental Biology, university of Michigan, 109 Zina Pitcher Place, 3063 Biomedical Sciences research Bldg (BSrB), Ann Arbor, MI 48109-2200, uSA [email protected]
Martin V. HübschmannDepartment of Cellular and Molecular Medicine, the Panum Institute, university of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark [email protected]
Christina KasperCMC Biopharmaceuticals A/S, Vandtårnsvej 83, 2860, Søborg, Denmark
Vladislav V. Kiselyovreceptor Systems Biology Laboratory, Hagedorn research Institute, Novo Nordisk A/S, Niels Steensens Vej 6, DK-2820 Gentofte, Denmark [email protected]
Jozsef Zoltan KissDepartment of Neuroscience, university of Geneva Medical School, 1, rue Michel Servet, CH-1211, Geneva, Switzerland [email protected]
P. KlauserDepartment of Neuroscience, university of Geneva Medical Center, 1. M. Servet, 1211 Geneva 4, Switzerland
Kateryna KolkovaProtein Laboratory, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, Panum Institute, university of Copenhagen, Building 24.2, Blegdamsvej 3C, DK-2200 Copenhagen, DenmarkEnkam Pharmaceuticals A/S, Fruebjergvej 3, Box 58, DK-2100 Copenhagen, Denmark [email protected]
Irina KorshunovaProtein Laboratory, Department of Neuroscience and Pharmacology, university of Copenhagen, Copenhagen, DenmarkENKAM Pharmaceuticals A/S, Copenhagen, Denmark [email protected]
xiv Contributors
Igor KraevDepartment of Life Sciences, The open university, Milton Keynes, MK7 6AA, uK
Lars V. KristiansenDepartment of Psychiatry and Behavioral Neurobiology, university of Alabama at Birmingham, Birmingham, AL, uSA [email protected]
Nikolaj KulahinENKAM Pharmaceuticals A/S, Copenhagen, Denmarkreceptor Systems Biology Laboratory, Hagedorn research Institute, Copenhagen, Denmark [email protected]
Shizhong LiENKAM Pharmaceuticals A/S, Fruebjergvej 3, Copenhagen Ø, DK-2100, Denmark [email protected]
Patricia F. ManessDepartment of Biochemistry and Biophysics, university of North Carolina, B#7260, 505 Mary Ellen Jones Building, Chapel Hill, NC 27599 [email protected]
Kamila MarkramLaboratory of Behavioral Genetics, Brain Mind Institute, EPFL, Lausanne, Switzerland
Nikolai MedvedevDepartment of Life Sciences, The open university, Milton Keynes, MK7 6AA, uK
P. MendezDepartment of Neuroscience, university of Geneva Medical Center, 1. M. Servet, 1211 Geneva 4, Switzerland
Mark MosevitskyDivision of Molecular and radiation Biophysics, Petersburg Nuclear Physics Institute, russian Academy of Sciences, Gatchina, Leningrad District, russia [email protected]
Martina MühlenhoffInstitute of Cellular Chemistry, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany
D. MullerDepartment of Neuroscience, university of Geneva Medical Center, 1. M. Servet, 1211 Geneva 4, Switzerland [email protected]
xvContributors
Janne NielsenProtein Laboratory, Department of Neuroscience and Pharmacology, Institute of Health Sciences, university of Copenhagen [email protected]
L. PogliaDepartment of Neuroscience, university of Geneva Medical Center, 1. M. Servet, 1211 Geneva 4, Switzerland
Victor PopovDepartment of Life Sciences, The open university, Milton Keynes, MK7 6AA, uK
Flemming M. Poulsenuniversity of Copenhagen, Department of Biology, ole Maaløes Vej 5 [email protected]
Gro Klitgaard PovlsenENKAM Pharmaceuticals, Fruebjergvej 3, DK-2100 Copenhagen Ø, Denmark [email protected]
Lars Christian B. RønnNeuroSearch A/S, Pederstrupvej 93, DK-2750 Ballerup, Denmark [email protected]
Urs RutishauserDepartment of Cell Biology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, uSA [email protected]
Carmen SandiLaboratory of Behavioral Genetics, Brain Mind Institute, EPFL, Lausanne, Switzerland [email protected]
Thomas SecherProtein Laboratory, Institute of Neuroscience and Pharmacology, Faculty of Health Sciences, university of Copenhagen, Copenhagen, DK-2200, Denmark [email protected]
Galina SkladchikovaDako Denmark A/S, DK-2600 Glostrup, Denmark
Vladislav SorokaNovo Nordisk A/S, Novo Nordisk Park, G6 S.154, DK-2760 Måløv, Denmark [email protected]
S. SteenDepartment of Neuroscience, university of Geneva Medical Center, 1. M. Servet, 1211 Geneva 4, Switzerland