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。定向细胞分裂和细胞极性的建立是许多生物发展的重要特征。酿酒酵母发芽的细胞还通过根据其细胞类型选择特定的芽位点，表现出简单，定义的定义细胞分裂模式。先前的遗传分析已导致鉴定出涉及酵母细胞形态发生的几个基因。 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。其中包括类似RAS的小GTP结合蛋白Bud1，GTPase激活蛋白（GAP）Bud2和鸟嘌呤核苷酸交换因子（GEF）Bud5。这三种蛋白质包含一个功能性GTPase模块，该模块通过引导另一组芽形成所需的蛋白质来确定萌芽位点。第二组蛋白质包括Rho样GTPase CDC42，CDC24和BEM1。据信，萌芽和肌动蛋白极化的空间控制涉及一系列GTPase，bud1控制Cdc42，最终控制肌动蛋白细胞骨架。 该提案旨在确定酵母萌芽过程中Bud1 GTPase模块在极性建立中的功能。 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节剂相互作用，以指导极性建立，以及（ii）Bud1 GTPase模块如何识别固有的空间提示以建立细胞型特定于特定的出现模式。为了实现这些目标，将实现遗传，生化和细胞生物学方法。关于酵母和哺乳动物细胞中与RAS相关的GTPase的最新研究使我们注意到了一种新的调节机制，用于细胞形态发生。了解Bud1 GTPase周期的功能将有助于我们揭示GTPase级联反应在极化肌动蛋白组织中的一系列形态发生事件。这项工作还将帮助我们了解人类癌症的起源机理，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。