The vertebrate neural cell adhesion molecule NCAM mediates heterophili
c adhesion to heparan sulfate proteoglycans in embryonic chick brain m
embranes. In this study, mouse L cells transfected with chicken NCAM w
ere used to identify two of these ligands as agrin and the target of t
he 6C4 monoclonal antibody. A third heparan sulfate proteoglycan, perl
ecan, appeared not to support NCAM-mediated adhesion. Enzymatic degrad
ation of chondroitin sulfates decreased adhesion in agrin-containing m
embrane fractions but increased adhesion if the agrin had previously b
een removed by immunoprecipitation, suggesting that interactions betwe
en heparan sulfate and chondroitin sulfate proteoglycans have importan
t influences on adhesion. Our experiments support the view that NCAM c
an interact with multiple, but not with all, heparan sulfate and chond
roitin sulfate proteoglycans in chick brain membranes in both positive
and negative ways to influence cell adhesion.