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© The Rockefeller University Press, 0021-9525/2000//1275 $5.00
The Journal of Cell Biology, Volume 149, Number 6, , 2000 1275-1288

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

^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

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

© 2000 The Rockefeller University Press

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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