Two antigenically related neuronal cell adhesion molecules of different specificities mediate neuron-neuron and neuron-glia adhesion (cell-cell adhesion/neuron-glia interaction/neural antigens/neural development/glial cells)

Previous studies in this laboratory have led to the identification of the neural cell adhesion molecule, N- CAM, a homophilic ligand that mediates adhesion between neurons as well as between neurons and striated muscle pre- cursors. By means of a similar immunological approach but with different assays, we have now identified a cell adhesion molecule on neurons (Ng-CAM) that mediates the heterotypic adhesion between neuronal membranes and glial cells. In this paper, we compare certain aspects of the structure and func- tion of Ng-CAM and embryonic N-CAM from the chicken. Ng- CAM was localized by specific antibodies on neurons but not on glia, and double-staining methods showed that individual neurons contained both Ng-CAM and N-CAM. Embryonic Ng-CAM migrates primarily as a single component of Mr 135,000; its apparent Mr shifted to 127,000 after neuramini- dase treatment. In contrast, the embryonic form of N-CAM migrates on NaDodSO4/polyacrylamide gels in the apparent Mr range of 200,000-250,000; after neuraminidase treatment, N-CAM migrates as two components of Mr 170,000 and Mr 140,000. Although both Ng-CAM and N-CAM have calcium- independent binding mechanisms, immunologically based cell adhesion assays suggested that they have different specificities in mediating cell adhesion. Whereas 0.25 ,ug of Ng-CAM par- tially neutralized the ability of 0.5 mg of polyspecific antineu- ral Fab' fragments to inhibit the heterotypic binding of neuro- nal membrane vesicles to glial cells and larger amounts of Ng- CAM completely neutralized this inhibition, 20 lug of N-CAM had no neutralization activity in this assay. Reciprocally, 0.25 lag of N-CAM partially neutralized the ability of 0.5 mg of the same Fab' fragments to inhibit the direct homotypic aggrega- tion of neuronal cells, but 20 ,ug of Ng-CAM had no detectable activity. Although peptide maps of the two cell adhesion mole- cules differed considerably and despite the differences in bind- ing specificity of these molecules, two independently derived monoclonal antibodies were found to crossreact with both Ng- CAM and N-CAM. Therefore, these different neuronal cell ad- hesion molecules with distinct binding specificities share at least one antigenic determinant, raising the possibility that they arose from a common evolutionary precursor.