Spatial regulation of exocytosis

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DESCRIPTION (provided by applicant): My goal is to understand how the Rho family of small GTPases control polarized exocytosis through the secretory vesicle docking complex, the exocyst. Spatial regulation of exocytosis is fundamental to many biological processes such as cell growth, polarity establishment, and cell-cell communication. Abnormalities in these fundamental processes may lead to pathological conditions such as cancer cell metastasis, neurological disorders, and kidney diseases. Polarized exocytosis involves directional transport, docking, and fusion of secretory vesicles with specific domains of the plasma membrane. An evolutionarily conserved multi-protein complex, the "exocyst" specifically localizes to sites of active secretion and serves as the basic vesicle docking machinery at the plasma membrane. Our recent studies using the budding yeast Saccharomyces cerevisiae revealed that Rho 1, a member of the Rho family of small GTP-binding proteins, interacts with the exocyst and regulate the localization of the exocyst during each stage of the cell cycle. Here we propose to identify and characterize the proteins involved in the signal transduction from Rho 1 to the exocyst using a combination of genetic, cytological, and biochemical approaches. Furthermore, we will test our hypothesis that Rho 1 interacts with the exocyst components to facilitate their polarized assembly at the plasma membrane. Finally, we will investigate how Rho 1 coordinates exocytosis with morphogenesis and polarized cell growth. These studies are crucial to our understanding of the molecular network controlling polarized secretion in eukaryotic cells.