Lipid-dependent regulation of exocytosis in by OSBP homolog (Osh) 4.

Polarized exocytosis is an essential process in many organisms and cell types for correct cell division or functional specialization. Previous studies established that homologs of the oxysterol-binding protein (OSBP) in , which comprise the Osh protein family, are necessary for efficient polarized exocytosis by supporting a late post-Golgi step. We define this step as the docking of a specific sub-population of exocytic vesicles with the plasma membrane. In the absence of other Osh proteins, yeast Osh4p can support this process in a manner dependent upon two lipid ligands, PI4P and sterol. Osh6p, which binds PI4P and phosphatidylserine, is also sufficient to support polarized exocytosis, again in a lipid-dependent manner. These data suggest that Osh-mediated exocytosis depends upon lipid binding and exchange without a strict requirement for sterol. We propose a two-step mechanism for Osh protein-mediated regulation of polarized exocytosis by using Osh4p as a model. We describe a specific role for lipid binding by an OSBP-related protein (ORP) in the process of polarized exocytosis, guiding our understanding of where and how OSBP and ORPs may function in more complex organisms.