SPATIAL CONTROL OF CELL POLARITY DURING YEAST BUDDING

酵母出芽过程中细胞极性的空间控制

• 批准号: 2752352
• 负责人: Hay-Oak Park
• 金额: $ 21.95万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2752352
• 关键词: cell cycle; cell cycle proteins; cellular polarity; guanosinetriphosphatases; intermolecular interaction; protein localization; protein structure function; yeasts

The long-term goal of this work is to understand the molecular basis of cellular morphogenesis. Oriented cell division and the establishment of cell polarity are essential features in the development of many organisms. Cells of the budding yeast Saccharomyces cerevisiae also exhibit simple, defined patterns of oriented cell divisions by choosing a specific bud site depending on their cell type. Previous genetic analyses have resulted in identification of several genes involved in yeast cell morphogenesis. Proteins encoded by these genes belong to highly conserved families of proteins in eukaryotes. These include the Ras-like small GTP binding protein Bud1, the GTPase Activating Protein (GAP) Bud2, and the Guanine nucleotide Exchange Factor (GEF) Bud5. These three proteins comprise a functional GTPase module that determines the site of budding by guiding another group of proteins that are necessary for bud formation. The second group of proteins includes the Rho-like GTPase Cdc42, Cdc24, and Bem1. It is believed that the spatial control of budding and actin polarization involves a cascade of GTPases, Bud1 controlling Cdc42, which ultimately controls the actin cytoskeleton. This proposal aims to determine the function of the Bud1 GTPase module in polarity establishment during yeast budding. Specific aims are to study: (i) how components of the Bud1 GTPase module interact with and modulate key regulators of the cytoskeleton to direct polarity establishment and (ii) how the Bud1 GTPase module recognizes the intrinsic spatial cues to establish the cell-type-specific budding pattern. To accomplish these goals, genetic, biochemical, and cell biological approaches will be undertaken. Recent work on Ras-related GTPases in yeast and mammalian cells have brought to our attention a new regulatory mechanism for cellular morphogenesis. Understanding the functions of the Bud1 GTPase cycle will help us to unravel the series of morphogenetic events culminating in polarized actin organization by a GTPase cascade. This work will also help us to understand the mechanism of genesis of human cancer since mutations in human homologs of these yeast proteins have been found in human tumor.

这项工作的长期目标是了解细胞形态发生的分子基础。细胞定向分裂和细胞极性的建立是许多生物发育的基本特征。发芽酵母的细胞也表现出简单、明确的定向细胞分裂模式，根据它们的细胞类型选择特定的芽位。以前的遗传分析已经鉴定出了几个与酵母细胞形态发生有关的基因。这些基因编码的蛋白质属于真核生物中高度保守的蛋白质家族。它们包括RAS样小GTP结合蛋白Bud1、GTP酶激活蛋白(GAP)Bud2和鸟嘌呤核苷酸交换因子(Global)Bud5。这三种蛋白质组成一个功能性的GTPase模块，它通过引导另一组芽形成所必需的蛋白质来确定发芽的位置。第二组蛋白包括Rho样GTP酶CDC42、CDC24和Bem1。人们认为，出芽和肌动蛋白极化的空间控制涉及一系列GTP酶，Bud1控制CDC42，最终控制肌动蛋白细胞骨架。这项建议旨在确定Bud1 GTPase模块在酵母发芽过程中的极性建立中的功能。具体目的是研究：(I)Bud1 GTPase模块的组件如何与细胞骨架的关键调控因子相互作用并调节其以指导极性的建立，以及(Ii)Bud1 GTPase模块如何识别固有的空间线索以建立特定细胞类型的出芽模式。为了实现这些目标，将采用遗传、生化和细胞生物学方法。最近在酵母和哺乳动物细胞中与Ras相关的GTP酶的研究工作引起了我们对细胞形态发生的新的调控机制的关注。了解Bud1 GTPase循环的功能将有助于我们解开一系列的形态发生事件，最终通过GTPase级联来极化肌动蛋白组织。这项工作也将帮助我们理解人类癌症的发生机制，因为在人类肿瘤中发现了这些酵母蛋白的人类同源物突变。