Cell-cell adhesion is critical in development and in the maintenance of histological integrity. In addition, recent studies suggest that alterations in cell-cell adhesion molecules (CAMs) may be important in such processes as tumor metastasis. The goal of our studies is to characterize in detail the structures of three cell surface glycoproteins involved in adhesion among cells of the chick embryo: the neural cell adhesion molecule, N-CAM, which is involved in the formation of nerve tissues and later in nerve-nerve and nerve-muscle interactions. The liver cell adhesion molecule, L-CAM, mediates the calcium-dependent aggregation of liver cells and is found on nearly all epithelial cells; Ng-CAM is a neuronal molecule involved in nerve-glia interactions. N-CAM and L-CAM appear in very early embryos and may be involved in initial pattern formation, whereas Ng-CAM appears later and may function in the refined organization of the nervous system. Comparable molecules have been identified in mammalian species, including man. We have described an overall linear model of the N-CAM molecule in terms of its binding region, unusual polysialic acid moieties and other prosthetic groups, and its association with the cell surface. We have also described a model of L-CAM in terms of N-linked oligosaccharides, phosphoamino acids and site of proteolytic release of the molecule from the cell surface. Protein chemical techniques and DNA cloning experiments will be used to determine the amino acid sequences of the N-CAM and L-CAM polypeptides and genes. Monoclonal antibodies and electron microscopy will also be used to refine our models of the molecules in detail. In vitro binding assays using N-CAM and its fragments will be used to correlate structural features with biological activity. Similar studies will be carried out on Ng-CAM. Detailed structural information will allow comparison of the CAMs with each other and with molecules involved in junctional complexes and cell-substrate adhesion. These studies should provide the necessary basis for defining precise mechanisms by which the CAMs contribute to the making and breaking of cell-cell contacts. A definition of adhesive mechanisms at this fundamental level will substantially increase our knowledge of their role in embryonic development and could have important consequences for understanding the origins of many birth defects, and a variety of pathological states.
Showing the most recent 10 out of 65 publications
