Smindak Richard J, Heckle Lindsay A, Chittari Supraja S, Hand Marissa A, Hyatt Dylan M, Mantus Grace E, Sanfelippo William A, Kozminski Keith G
Department of Biology, University of Virginia, Charlottesville, VA 22904, USA.
Department of Biology, University of Virginia, Charlottesville, VA 22904, USA
J Cell Sci. 2017 Nov 15;130(22):3891-3906. doi: 10.1242/jcs.205435. Epub 2017 Oct 9.
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.
极化胞吐作用在许多生物体和细胞类型中是正确细胞分裂或功能特化的一个重要过程。先前的研究表明，酿酒酵母中包含Osh蛋白家族的氧甾醇结合蛋白（OSBP）的同源物，通过支持高尔基体后晚期步骤，对于有效的极化胞吐作用是必需的。我们将这一步骤定义为特定亚群的分泌囊泡与质膜的对接。在没有其他Osh蛋白的情况下，酵母Osh4p可以以依赖于两种脂质配体PI4P和甾醇的方式支持这一过程。结合PI4P和磷脂酰丝氨酸的Osh6p同样足以以脂质依赖的方式支持极化胞吐作用。这些数据表明，Osh介导的胞吐作用依赖于脂质结合和交换，而对甾醇没有严格要求。我们以Osh4p为模型，提出了一个Osh蛋白介导的极化胞吐作用调控的两步机制。我们描述了OSBP相关蛋白（ORP）的脂质结合在极化胞吐作用过程中的特定作用，引导我们理解OSBP和ORP在更复杂生物体中可能发挥作用的位置和方式。
