Polarized Exocytosis: Rabs, Tethers, and SNAREs

极化胞吐作用：Rab、Tether 和 SNARE

• 批准号: 10473760
• 负责人: PATRICK J BRENNWALD
• 金额: $ 44.57万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10473760
• 关键词: Address; Alleles; Binding; Binding Sites; Biochemical; Biochemical Genetics; Biological Assay; Cell membrane; Cell surface; Cells; Collaborations; Complex; Cryoelectron Microscopy; Cues; Data; Defect; Development; Disease; Exocytosis; Funding; Genetic; Goals; Golgi Apparatus; Growth; Guanosine Triphosphate Phosphohydrolases; Homologous Gene; Human; In Vitro; Insulin; Investigation; Label; Laboratories; Lipids; Malignant Neoplasms; Mediating; Membrane; Molecular; Neurons; Non-Insulin-Dependent Diabetes Mellitus; Pathway interactions; Pattern; Peptides; Phosphatidylinositols; Process; Property; Protein Family; Proteins; Publishing; Regulation; Regulatory Pathway; Resolution; Role; SNAP receptor; Side; Structural Models; Structure; Surface; System; Vesicle; Work; Yeasts; combat; gain of function; genetic manipulation; human disease; loss of function; member; mimetics; mutant; novel strategies; novel therapeutics; rab GTP-Binding Proteins; reconstitution; rho; rho GTP-Binding Proteins; tool; trafficking; tumor

Abstract The overall goal of this proposal is to understand the mechanism by which Rho GTPases, Rab GTPases, tethering agents, and SNAREs contribute to direct polarized trafficking and growth at the cell surface. Previous work from our laboratories and others has implicated members of the Rho/Cdc42, exocyst and Sro7/Tomosyn protein families as highly conserved factors that have important roles in both polarity and membrane trafficking to the cell surface in systems as diverse as yeast and neurons. In this proposal, we will make use of new biochemical, genetic, and structural tools we have developed during the previous funding period to examine the molecular mechanisms by with Exocyst and Sro7 proteins work together as Rab effectors and vesicle tethering agents. Importantly we make use of newly identified gain-of-function alleles within the exocyst and Sro7 to understand the distinct biochemical and structural changes that occur to these tethering agents as they respond to regulatory and spatial cues.

摘要 这项建议的总体目标是了解Rho GTP酶的机制， RAB GTP酶、绑定剂和圈套有助于直接极化的贩运和生长 在细胞表面。我们实验室和其他机构之前的工作表明， Rho/CDc42、胞外囊和Sro7/Tomosyn蛋白家族是高度保守的因子，具有 在不同的系统中，在极性和膜向细胞表面运输方面都扮演着重要的角色 作为酵母菌和神经元。在这个提案中，我们将利用新的生化、遗传和 我们在上一次资助期间开发的结构工具，用于检查分子 外囊和Sro7蛋白作为Rab效应器和囊泡共同作用的机制 系链剂。重要的是，我们利用了新发现的功能增益等位基因 胞囊和Sro7，以了解这些细胞发生的明显的生化和结构变化 当它们对监管和空间线索做出反应时，系留代理。