Polarized Exocytosis: Rabs, Tethers, and SNAREs

极化胞吐作用：Rab、Tether 和 SNARE

• 批准号: 10264083
• 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/10264083
• 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; Genetic Structures; 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 本提案的总体目标是了解Rho GTP酶的机制， Rab GTP酶、栓系剂和SNARE有助于直接极化贩运和增长 在细胞表面。我们的实验室和其他人以前的工作表明， Rho/Cdc 42、exocyst和Sro 7/Tomosyn蛋白家族作为高度保守的因子， 在极性和膜运输到细胞表面的系统中的重要作用， 酵母和神经元一样。在这项建议中，我们将利用新的生物化学，遗传学和生物学方法， 我们在上一个资助期开发的结构工具， 外囊和Sro 7蛋白作为Rab效应子和囊泡共同作用的机制 系留代理。重要的是，我们利用新鉴定的功能获得性等位基因， 外囊和Sro 7，以了解这些细胞发生的独特的生化和结构变化， 系留剂，因为它们响应于调节和空间线索。