REGULATION OF MYELIN-ASSOCIATED GLYCOPROTEIN BINDING BY SIALYLATED CIS-LIGANDS

Myelin-associated glycoprotein (MAG) and Schwann cell myelin protein ( SMP) are highly glycosylated members of a newly defined family of cell adhesion molecules belonging to the immunoglobulin superfamily that r ecognize terminal sialic acid residues on N- and O-linked oligosacchar ides. The importance of the N-linked oligosaccharides on MAG were dete rmined by removal of the eight predicted carbohydrate addition sites b y site-directed mutagenesis. The results suggest that all eight N-link ed glycosylation sites are utilized in COS cells. N-linked glycosylati on does not appear to be required for sialic acid-dependent MAG bindin g to erythrocytes. However, N-linked glycosylation of MAG does play a role in the proper folding of MAG. It was also shown that sialylation in the host cell expressing MAG and SMP could inhibit binding to eryth rocytes. The degree to which SMP and MAG erythrocyte binding was affec ted by sialylation in the host cell was dependent on (a) the level at which MAG was expressed on the surface of the host cell and (b) the pr esence of MAG ligands on the host cell. The data suggest that cis-liga nds on the host cell compete with trans-ligands on the target cell for the binding site(s) on MAG.