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J. Cell Biol. 149 (6): 1275-1288

Copyright © 2000 by the Rockefeller University Press.

Original Article

Coordinate Regulation of Cadherin and Integrin Function by the Chondroitin Sulfate Proteoglycan Neurocan

Hedong Lia, Tin-Chung Leunga, Stanley Hoffmanb, Janne Balsamoa, , and Jack Liliena

a Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202
b Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, South Carolina 29425-2229
Department of Biological Sciences, Wayne State University, Detroit, MI 48202.(313) 577-6891(313) 577-0133

jlilien{at}biology.biosci.wayne.edu

Abstract: N-cadherin and β1-integrins play decisive roles in morphogenesis and neurite extension and are often present on the same cell. Therefore, the function of these two types of adhesion systems must be coordinated in time and space to achieve the appropriate cell and tissue organization. We now show that interaction of the chondroitin sulfate proteoglycan neurocan with its GalNAcPTase receptor coordinately inhibits both N-cadherin– and β1-integrin–mediated adhesion and neurite outgrowth. Furthermore, the inhibitory activity is localized to an NH2-terminal fragment of neurocan containing an Ig loop and an HA-binding domain. The effect of neurocan on β1-integrin function is dependent on a signal originating from the cadherin cytoplasmic domain, possibly mediated by the nonreceptor protein tyrosine kinase Fer, indicating that cadherin and integrin engage in direct cross-talk. In the developing chick, neural retina neurocan is present in the inner plexiform layer from day 7 on, and the GalNAcPTase receptor becomes restricted to the inner nuclear layer and the ganglion cell layer (as well as the fiber layer), the two forming a sandwich. These data suggest that the coordinate inhibition of cadherin and integrin function on interaction of neurocan with its receptor may prevent cell and neurite migration across boundaries.

Key Words: cadherin • integrin • adhesion • neurite outgrowth • tyrosine kinase Fer

The present address of H. Li is Neuroscience Center, Nelson Biological Laboratories, 604 Allison Road, Rutgers University, Piscataway, NJ 08854-8082. The present address of T.C. Leung is Department of Developmental Biology, Institute Biology I, University of Freiburg, Hauptstrasse 1, D-79104 Freiburg, Germany. The present address of J. Balsamo and J. Lilien is Department of Biological Sciences, University of Iowa, Iowa City, IA 52242-1324.

Abbreviations used in this paper: 250kD PG, 250-kD chondroitin sulfate proteoglycan; CBP, catenin binding peptide; COP, control antennapedia peptide; GalNAcPTase, cell-surface glycosyltransferase; HA, hyaluronic acid; IPL, inner plexiform layer; JMP, juxtamembrane peptide; OPL, outer plexiform layer.

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