Evolutionary conservation of key structures and binding functions of neural cell adhesion molecules.

Abstract
The neural cell adhesion molecule (N-CAM) is a sialic acid-rich, cell surface glycoprotein that mediates cell adhesion by a homophilic mechanism. Its binding function was implicated in both morphogenesis and histogenesis; during development it changes in amount at the cell surface and perinatally it undergoes a decrease in sialic acid content (embryonic .fwdarw. adult conversion) with an increase in binding efficacy. Salient aspects of the structure and the mutual binding specificities of N-CAM from a variety of vertebrate species were examined to determine whether (N-CAM)-mediated adhesion mechanisms were conserved during evolution. N-CAM immunoreactivity was detected in a series of polypeptides of characteristic MW extracted from brain tissues of all vertebrate species tested, including mammals, birds, reptiles, amphibia and bony and cartilaginous fish. Adhesion mediated by N-CAM occurred across species lines as indicated by the co-aggregation of chicken and mouse neural cells. By using a quantitative membrane vesicle aggregation assay, the efficacy of cross-species brain membrane vesicle adhesion in various pairings (chicken-mouse, chicken-frog, mouse-frog) was found to be similar to the efficacy of intra-species adhesion. Effective cross-species aggregation of brain membrane vesicles also occurred in embryonic-embryonic, adult-adult, and embryonic-adult pairings. In a control experiment, embryonic chicken liver membrane vesicles (which do not contain N-CAM) did not co-aggregate with embryonic chicken brain membrane vesicles. Cross-species co-aggregation could be inhibited by Fab'' fragments of antibodies to N-CAM and was most effectively inhibited in the presence of mixtures made from the Fab'' fragments of specific antibodies prepared against the N-CAM from each of the animal species constituting a co-aggregating pair. In accord with the proposed role of N-CAM as a regulator of morphogenesis, both the specificity of the binding region of the molecule and its basic chemical structure were highly conserved during evolution.

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