NEUROTRANSMITTER FUNCTION IN C. ELEGANS

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Neurotransmitters are released into the synaptic cleft using a common set of proteins involved in synaptic vesicle exocytosis and endocytosis. By contrast, certain synaptic proteins must be tailored to the needs of each specific neurotransmitter. These neurotransmitter-specific functions include biosynthetic enzymes, transporters for translocation across vesicular and plasma membranes, and specialized receptors on the postsynaptic surface. My laboratory is engaged in a longterm project to identify the gene products required by specific neurotransmitters. We are taking a genetic approach in the nematode Caenorhabditis elegans to identify mutants defective for the functions of a specific neurotransmitter, we then clone the cognate genes and characterize the proteins using biochemical assays. We propose to identify and characterize three proteins which function in neurotransmission: (1) the vesicular glutamate transporter, which as yet, remains uncharacterized, (2) a potential ancillary protein to the vesicular GABA transporter encoded by the unc-46 gene, (3) a novel excitatory GABA receptor encoded by the exp-1 gene. These studies are likely to result directly in the identification of vertebrate homologs of these proteins. Eventually, these experiments will lead to a better understanding of how the molecular structures of these proteins confer their functional properties. Ultimately, these studies might help explain the molecular behavior of neuroactive drugs and lead to the development of new and more specific pharmaceuticals which act on individual neurotransmitter systems.