Abstract #49

Yeast Oxysterol-Binding Proteins affect Cdc42p- and Rho1p-mediated cell polarization. Christopher Beh¹, Gabriel Alfaro¹, Shubha Dighe², Keith Kozminski². 1) Department of Molecular Biology & Biochemistry, Simon Fraser University, Burnaby, BC, Canada; 2) Departments of Biology & Cell Biology, University of Virginia, Charottesville, VA.
   Polarized cell growth requires the establishment of an axis of growth along which secretion can be targeted to a specific site on the cell cortex. How polarity establishment and secretion are choreographed is not fully understood, though Rho and Rab GTPase-mediated signaling is required. Superimposed on this regulation are functions of specific lipids and their cognate binding proteins. In a dosage suppression screen for genes that interact with Rho-family CDC42 to promote polarity establishment, we identified KES1/OSH4, which encodes one of seven yeast Oxysterol-Binding Protein (OSBP) homologues (OSH1-OSH7). In humans and budding yeast, OSBPs represent a multigene family implicated in sterol transport and cell signaling. We previously showed that individual OSH genes are not essential but that the entire gene family is collectively required for cell viability. In the absence of the other family members, each individual OSH gene has the capacity to provide the essential function of the entire gene family. To determine the overlapping essential activities of the OSH family, we created strains in which all OSH function could be concomitantly repressed or inactivated. With these strains, we established that the OSH genes are involved in polarized cell growth. The OSH gene family is necessary to maintain the proper localization of specific proteins necessary for proper bud formation, including Cdc42p, Rho1p, septins, and Sec4p. Disruption of all OSH gene function also caused specific defects in polarized exocytosis, indicating the Osh proteins are collectively required for the function of a specific secretory pathway implicated in polarized cell growth. At different points in the cell cycle, OSH genes differentially affected CDC42 and RHO1 signaling, suggesting a model wherein Osh proteins promote polarized secretion only after cell polarity is established. Our findings suggest that OSBPs link sterol-mediated cell signaling to the control of cell polarization.

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