The Distribution and Function of PI4P During Osh-dependent Polarized Secretion in Saccharomyces cerevisiae 169 views

Polarized secretion is an essential cellular process in which vesicles release exocytic cargo at one pole of the cell after trafficking from the trans-Golgi to the PM. Many studies in the budding yeast S. cerevisiae have identified conserved proteins required for vesicle maturation, a process that converts a PM docking incompetent vesicle to a PM docking competent state. However, the role of lipids in vesicle maturation is less well studied. In the current model for polarized secretion, the lipid transfer protein Osh4p is posited to mediate a loss of vesicle-associated PI4P that drives vesicle maturation. Currently, it is unclear whether other Osh proteins can substitute for Osh4p to support polarized secretion. Due to a lack of direct data, it is also unclear whether vesicle-associated PI4P decreases in an Osh-dependent manner. In this dissertation, I demonstrate Osh6p can independently support polarized secretion in a lipid-dependent manner. I also show that deletion of OSH4 does not alter vesicle-associated PI4P levels, though loss of any individual member of the OSH family or complete loss of OSH family function alters the intracellular distribution of PI4P. I propose a new model for polarized secretion in which the Rab GTPases Ypt32p and Sec4p remain associated with a secretory vesicle during trafficking, independent of PI4P levels and Osh4p. In addition, I highlight that despite sharing a yet unknown function, Osh protein family members play unique roles in establishing and/or maintaining intracellular lipid distribution. Together, these findings provide a strong framework to guide future high spatial and temporal resolution studies of lipids and ORPs in yeast and mammalian cells to elucidate the function of proteins in polarized secretion.

PHD (Doctor of Philosophy)

English

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2023-07-11