Regulation of Cell Polarity and Exocytosis

描述(申请人提供)：这项建议的总体目标是了解真核细胞将极化的生长和分泌引导到细胞表面特定位置的机制，以及这如何与整体细胞极性相协调。我们实验室和其他人之前的工作表明，LGL/Sro7和Rho/Cdc42蛋白家族的成员在许多系统中的细胞膜运输和细胞极性方面都发挥着重要作用。酵母细胞表面运输的空间调控需要特定的Rho/CDC42定位模式以及对LGL/Sro7蛋白的囊泡连接和融合功能的严格调控。在这项提案中，我们将研究结构 CDC42和Rho3GTPase蛋白中的元件对于它们不同的定位模式至关重要，并定义了特定的内吞因子和途径，用于回收和运输CDC42到细胞表面。最后，我们将以我们最近发现的Sro7依赖于RAB的囊泡对接功能为基础，剖析Sro7‘S在囊泡对接和融合中的分子内和分子间调节。

DESCRIPTION (provided by applicant): The overall goal of this proposal is to understand the mechanism by which eukaryotic cells direct polarized growth and secretion to specific sites on the cell surface and how this is coordinated with overall cell polarity. Previous work from our laboratory and others has implicated members of the Lgl/Sro7 and Rho/Cdc42 protein families as factors that have important roles in both membranes trafficking to the cell surface and cell polarity in a number of systems. Spatial regulation of trafficking on the cell surface in yeast requires specific patterns of Rho/Cdc42 localization as well as tight regulation of vesicle tethering and fusion functions of Lgl/Sro7 protein. In this proposal we will examine the structural elements in Cdc42 and Rho3 GTPase proteins that are critical for their distinct patterns of localization and define the specific endocytic factors and pathways utilized for recycling and trafficking of Cdc42 to the cell surface. Finally we will build on our recent discovery of a Rab-dependent vesicle docking function of Sro7 to dissect both the intra and intermolecular regulation of Sro7's dual functions in vesicle docking and fusion.