Polarized Exocytosis: Rabs, Tethers, and SNAREs

Project Title: Polarized Exocytosis: Rabs, Tethers and SNAREs Abstract: The overall goal of this proposal is to understand how regulation and coordination of exocytosis and cell polarity is achieved within the cell. Our laboratory has played a central role in determining how Rho/Cdc42 GTPases, the exocyst, and Sro7/Tomosyn family members act in Rab and SNARE-mediated cell surface trafficking. We were the first to suggest that exocyst works as a highly regulated machine directing polarized trafficking and growth to specific sites at the cell surface. In this proposal, we will delineate the mechanism by which exocyst is allosterically regulated, model this regulation in both yeast and mammalian systems, and test the conservation of this activation using a mouse adipocyte model of regulated exocytosis. Finally, we will detail the role of specific phosphoinositide lipids in exocyst tethering, as well as deliver novel structural insights into how Sro7/tomosyn family members are regulated and act as vesicle tethers in exocytosis.