A ROLE FOR POLYSIALIC ACID IN NEURAL CELL-ADHESION MOLECULE HETEROPHILIC BINDING TO PROTEOGLYCANS

The neural cell adhesion molecule (NCAM) is known to participate in bo th hemophilic and heterophilic binding, the latter including mechanism s that involve interaction with proteoglycans. The polysialic acid (PS A) moiety of NCAM can serve as a negative regulator of hemophilic bind ing, but indirect evidence has suggested that PSA can also be involved in heterophilic binding. We have examined this potential positive rol e for PSA in terms of the adhesion of PSA-expressing mouse F11 cells a nd chick embryonic brain cells to substrates composed of the purified heparan sulfate proteoglycans agrin and 6C4. This adhesion was specifi cally inhibited by polyclonal anti-NCAM Fab antibodies, monoclonal ant i-PSA antibodies, PSA itself, and enzymatic removal of either PSA or h eparan sulfate side chains. By contrast, the adhesion was not affected by chondroitinase, and cell binding to laminin was not inhibited by a ny of these treatments. A specific NCAM-heparan sulfate interaction in this adhesion was further indicated by its inhibition with monoclonal anti-NCAM Feb antibodies that recognize the known heparin-binding dom ain of NCAM and with the HBD-2 peptide derived from this region, but n ot with antibodies directed against other regions of the protein inclu ding the homophilic binding region. Together, the results suggest that PSA can act in vitro either as a receptor in NCAM heterophilic adhesi on or as a promoter of binding between een heparan sulfate proteoglyca ns and the NCAM heparin-binding domain.