The common objective of these projects is to exploit and test the various clues that have recently come to light on the functions of gangliosides in the nervous system. Thus, our recent discovery that gangliosides are present at relatively high levels in synaptic vesicles of Torpedo (and possibly other species) provides an opportunity to investigate their role in neurosecretion. As a first step we shall determine the structures and distributional pattern of molecular species in this organelle and compare them to the structures and distributional pattern of pre-synaptic membrane from the same source. The neuritogenic effect which exogenous gangliosides assert on cultured neurons and certain neuronally- derived cells lines will be studied from the standpoint of mechanism and also by comparing the ganglioside patterns and synthesis potential of responding vs non-responding cells. We shall attempt to determine which pool of exogenous gangliosides causes the effect. These studies will probe the role of differentiation-associated gangliosides in the normal differentiation of neurons. We shall continue our study of gangliosides of the peripheral nervous system, testing our hypothesis that ganglio-type structures are common to all neurons of the CNS and PNS. This system will also be used to study ganglioside role(s) in regeneration. The two ganglioside transfer proteins we have isolated from calf brain will be further purified and characterized as to glycolipid specificity. Their cellular and subcellular localization within brain will be studied by use of antibodies. We shall explore their use as research tools for modifying glycolipid composition of membranes. This will include examination of possible heterogeneity of composition in such membranes from different brain regions and different neuronal types. Using cell culture systems, we shall determine whether growth cone membranes have unique gangliosides not characteristics of the remainder of the differentiating neuron.
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