Polarized Exocytosis: Rabs, Tethers, and SNAREs

极化胞吐作用：Rab、Tether 和 SNARE

基本信息

批准号：
10119488
负责人：
PATRICK J BRENNWALD
金额：
$ 45.72万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
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/10119488
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

项目摘要

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.

抽象的该提案的总体目标是了解Rho GTPases的机制 Rab GTPases，束缚剂和网罗有助于直接两极分化和增长在细胞表面。我们实验室和其他人的先前工作牵涉到 Rho/cdc42，exocyst和sro7/tomosyn蛋白家族是具有高度保守的因素在系统中的极性和膜运输到细胞表面的重要作用，因为多样化作为酵母和神经元。在此提案中，我们将利用新的生化，遗传和我们在上一个资金期间开发的结构工具以检查分子用外囊肿和SRO7蛋白通过RAB效应子和囊泡一起工作的机理绑扎剂。重要的是，我们利用新近确定的功能奖励等位基因外囊肿和SRO7了解这些发生的独特的生化和结构变化束缚代理人对监管和空间提示做出反应。