Exocytotic release of hormones and neurotransmitters is central to intercellular communication and synaptic transmission and is fundamental to the normal function of the endocrine, cardiovascular and nervous systems. The long-term goal of the application is to understand the biochemical and physiological mechanisms underlying regulated exocytosis. Specifically, this application will elucidate the role of rabphilin3a in the pathway. Rab GTPases are involved in vesicular trafficking in the secretory and endocytotic pathways. Rabphilin3a was identified in brain as a possible effector for rab3a. The investigators recently found that rabphilin3a is expressed with rab3a in adrenal chromaffin cells and enhances calcium dependent secretion. The focus of this proposal is to investigate the mechanisms by which rabphilin3a functions in regulated exocytosis. The proposal will: 1) elucidate the mechanism by which rabphilin3a enhances exocytosis in bovine adrenal chromaffin cells using both biochemical and electrophysiological measures of secretion. 2) Determine the relationship between subcellular localization of rabphilin3a and mutants and function in secretion. 3) Investigate possible new members of the rabphilin3a pathway including adducin. A variety of techniques will be used to study rabphilin3a function in chromaffin cells including transient-expression approach for biochemical studies of secretion and electrophysiological/microamperometric techniques from single cell studies.
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