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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1984 Nov;81(21):6881–6885. doi: 10.1073/pnas.81.21.6881

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

S Hoffman, C M Chuong, G M Edelman
PMCID: PMC392036  PMID: 6208560

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 has been 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--adult conversion) with an increase in binding efficacy. In the present study, salient aspects of the structure and the mutual binding specificities of N-CAMs from a variety of vertebrate species were examined to determine whether (N-CAM)-mediated adhesion mechanisms have been conserved during evolution. N-CAM immunoreactivity was detected in a series of polypeptides of characteristic molecular weight 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 of N-CAM and was most effectively inhibited in the presence of mixtures made from the Fab' fragments of specific antibodies prepared against the N-CAMs from each of the animal species constituting a co-aggregating pair. These results suggest that, 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 have been highly conserved during evolution.

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Selected References

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