Ganglioside transport within and between brain cells continues to be a major theme of our research. Having previously established that fast anterograde transport is the mechanism for transfer of gangliosides from the cell body (where they are synthesized) to axonal and nerve-ending membranes, we are now studying retrograde transport. We are using the double-ligation paradigm with motoneurons of the rat sciatic nerve, and observe fast retrograde transport of both gangliosides and glycoproteins. Our next objective is to compare molecular species moving in the anterograde and retrograde directions, both in normal and regenerating nerve. Detailed structure analysis will be carried out for gangliosides of motor and sensory neurons, capitalizing on the specific radio-labeling that arises from use of different injection sites. Preliminary data indicate another mode of ganglioside transport in brain - that which is catalyzed by a gnaglioside (glycolipid) transfer protein. We shall study this protein and its ability to catalyze ganglioside movement between neural membranes and between cells. The nature and origin of astrocytic gangliosides remains a paradox which we shall attempt to solve through a variety of approaches; one possibility being considered is that gangliosides are transferred to astrocytes from neurons, possibly through mediation of the transfer protein. The neuritogenic effect of gangliosides will be studied employing primary cultures of increasing complexity: pure neurons, mixed neurons and glia, and organotypic cultures. These will serve as models for probing the role which gangliosides may have in neuronal differentiation. We shall compare the effects of many different gangliosides, added alone and in the presence of the transfer protein which is expected to significantly alter the ganglioside composition of the neuronal membrane. Finally, we shall determine the lipid profile of growth cone membranes with special emphases on gangliosides and neutral glycosphingolipids.
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