The eucaryotic cell surface has been implicated in the control of cell adhesion, growth, motility, morphology and differentiation. Presumably, this is accomplished via specific cell surface receptors which """"""""sense"""""""" the cell's molecular and cellular environment and allow the cell to respond accordingly. These control mechanisms are central in the process of orderly morphogenesis and in neoplastic transformation and metastasis. The most highly regulated example of cell surface interactions may be in the development of the vertebrate nervous system, where neurons may be coded to make specific connections with appropriate target cells. The molecular mechanisms for such interactions are unknown, and their elucidation remains a major challenge. This proposal investigates the role of a major class of cell surface molecules -- complex carbohydrates (particularly gangliosides) -- in controlling cell surface interactions in neuronal cells. Neuroblastoma cells in tissue culture and cells dissociated from embryonic neural tissues are used in our studies. Two experimental approaches are in progress: 1. """"""""Cell Surface Analogs"""""""". Incubation of intact cells with carbohydrate-derivatized surfaces led to the demonstration of carbohydrate-specific adhesion followed by post-adhesion cellular responses. This novel approach will be used to directly test the ability of particular synthetic carbohydrates, neutral glycosphingolipids, or gangliosides to support specific adhesion of clonal or primary neuronal cells. Demonstration of carbohydrate recognition by neuronal cells will lead to studies on the identification of the receptors involved and their control during neuronal differentiation. 2. Regulation of the ganglioside metabolism during neuronal differentiation. A hybrid neuroblastom x glioma cell line which displays many developmental characteristics of nerve cells will be used to study the metabolism of gangliosies in response to controlled differentiation. Our previous results indicate that the ganglioside composition of these cells is closely controlled during differentiation in vitro. The enzymes which may be involved in this control, ganglioside glycosyltransferases and glycosidases, will be measured as a function of cellular differentiation.
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