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.

While glia were once thought to be nothing more than glue‐like cells that hold the nervous system together, there is growing evidence that signals to and from glia are indispensable for development, cell‐to‐cell communication and maintenance of efficient nervous system function. Several studies show that glia often receive conflicting signals during disease progression and can play dual roles as both antagonists and neuroprotectors in distinct settings. Key Concepts Glia play neuroprotective and neurodegenerative role during the initiation and progression stage of neurodegenerative diseases. Astrocytes mediate calcium‐related neurotoxicity in Alzheimer's disease. Microglia regulate neurodegeneration in Parkinson's disease through NO‐related apoptotic pathway. Oligodendrocytes and Schwann cells regulate myelin wasting diseases in central and peripheral nervous system through Wnt and ErbB2/ErbB3 signalling pathways. Glial cells form a scar following spinal cord injury that affects regenerative abilities.

Polarized secretion facilitates polarized cell growth. For a secretory vesicle to dock at the plasma membrane, it must mature with a progressive association or dissociation of molecules that are, respectively, necessary or inhibitory to vesicle docking, including an exchange of Rab GTPases. In current models, oxysterol binding protein homologue 4 (Osh4p) establishes a PI4P gradient along the secretory trafficking pathway such that vesicles have higher PI4P levels after budding from the trans-Golgi relative to when vesicles arrive at the plasma membrane. In this study, using the lipid binding domain P4M and live cell imaging, we show that secretory vesicle-associated PI4P levels remain constant when vesicles traffic from the trans-Golgi to the plasma membrane. We 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. We propose a model in which the Rab GTPases Ypt32p and Sec4p, remain associated with a secretory vesicle during trafficking, independent of PI4P levels and Osh4p. Together these data indicate the necessity of experiments revealing the location and timing of events required for vesicle maturation. [Media: see text] [Media: see text] [Media: see text] [Media: see text]