Two antigenically related neuronal cell adhesion molecules of different specificities mediate neuron-neuron and neuron-glia adhesion.

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Abstract
The neural cell adhesion molecule, N-CAM, a homophilic ligand that mediates adhesion between neurons as well as between neurons and striated muscle precursors was identified. By means of a similar immunological approach but with different assays, a cell adhesion molecule on neurons (Ng-CAM) that mediates the heterotypic adhesion between neuronal membranes and glial cells was also identified. The structure and function of Ng-CAM and embryonic N-CAM from the chicken are compared. Ng-CAM was localized by specific and embryonic N-CAM 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 MW 135,000; its apparent MW shifted to 127,000 after neuraminidase treatment. The embryonic form of N-CAM migrates on NaDodSO4/polyacrylamide gels in the apparent MW range of 200,000-250,000; after neuraminidase treatment, N-CAM migrates as 2 components of MW 170,000 and MW 140,000. Although both Ng-CAM and N-CAM have C-independent binding mechanisms, immunologically based cell adhesion assays suggested that they have different specificities in mediating cell adhesion. Whereas 0.25 .mu.g of Ng-CAM partially neutralized the ability of 0.5 mg of polyspecific antineural Fab'' fragments to inhibit the heterotypic binding of neuronal membrane vesicles to glial cells and larger amounts of Ng-CAM completely neutralized this inhibition, 20 .mu.g of N-CAM had no neutralization activity in this assay. Reciprocally, 0.25 .mu.g of N-CAM partially neutralized the ability of 0.5 mg of the same Fab'' fragments to inhibit the direct homotypic aggregation of neuronal cells, but 20 .mu.g of Ng-CAM had no detectable activity. Although peptide maps of the 2 cell adhesion molecules differed considerably and despite the differences in binding specificity of these molecules, 2 independently derived monoclonal antibodies were found to crossreact with both Ng-CAM and N-CAM. These different neuronal cell adhesion molecules with distinct binding specificities share at least 1 antigenic determinant, raising the possibility that they arose from a common evolutionary precursor.