MECHANISM OF NEURITE FORMATION

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Gangliosides have been found to enhance neuritogenesis by neuroblastoma cel s in vitro , and to enhance nerve regeneration in vivo. Recently the oligosaccharide moieties of gangliosides have also been found to enhance neuritogenesis by neuroblastoma cells, suggesting the presence of a cell surface receptor. This hypothesis is supported by the observation that viab e neural retina cells can bind to gangliosides adsorbed to plastic via a trypsin sensitive mechanism. This proposal asks two fundamental questions concerning these observations: 1) how much exogenous ganglioside actually reaches the lesioned area within the brain where it putatively enhances neuritogenesis?; and 2) how does the ganglioside interact with the neuroblastoma or neuron? To answer the first question autoradiographic experiments will be carried out to determine the distribution of labeled ganglioside in the brains of lesioned and unlesioned rats. To answer the second question, experiments will be carried out to determine whether ganglioside responsive neuroblastoma cells have cell surface receptors capable of recognizing the oligosaccharide moiety of the appropriate gangli - side. If receptors are identified they will be isolated and characterized. Primary cultures of neurons will also be assayed for the presence of ganglioside-oligosaccharide cell surface receptors. To determine the effect of this interaction on "differentiation" properties defined as associated with neuronal maturation will be monitored. To determine a possible mechani m for transmitting the binding into an intracellular response, the effect of the ganglioside and the corresponding oligosaccharide on the phosphorylatio activity of the cell plasma membranes will be determined.