G Protein Regulation of a Microtubule Motor Protein in Yeast

酵母中微管运动蛋白的 G 蛋白调节

• 批准号: 0453964
• 负责人: David Stone
• 金额: --
• 依托单位: University of Illinois at Chicago
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-15 至 2010-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0453964&HistoricalAwards=false
• 关键词: Protein; Regulation; Microtubule; Motor; Yeast

Cellular polarization is essential to morphogenesis, immune response, neuronal development, chemotropism, and motility. Saccharomyces cerevisiae is a well-studied model eukaryote that exhibits numerous polarization phenomena, including signal-induced changes in cell shape and nuclear position. During the haploid phase of their life cycle, yeast cells secrete peptide pheromones that transform vegetatively growing cells of opposite mating type into gametes. Preparatory to cellular and nuclear fusion, pheromone triggers polarized growth toward the mating partner (chemotropism), and migration of the nucleus to the tip of the mating projection. Recent results implicate the pheromone-responsive G-alpha protein, Gpa1, in the control of signal-induced polarized growth and nuclear movement. In cells responding to pheromone, Gpa1 interacts directly with the mating-specific MAPK protein, Fus3, and with Kar3, a microtubule motor protein that is essential for nuclear movement during mating. Disruption of the Gpa1-Fus3 interaction confers defects in chemotropism, microtubule orientation, and nuclear migration. The long-term goal of this project is to understand how G alpha proteins regulate the microtubule cytoskeleton in response to external signals. To this end, genetic, biochemical, mass spectrometric, and imaging approaches will be used to determine how Gpa1 affects the mating-specific functions of Kar3, and whether Fus3 is involved in this regulation. Because Gpa1 and Kar3 provide the first example of a G alpha protein/motor-protein interaction, and because G alpha regulation of nuclear movement is unprecedented, this analysis promises to be informative. This project will also provide significant training opportunity. A graduate student and a postdoctoral fellow will be working on several aspects of the research. In addition, a high school student will be recruited to participate in the project each summer.

细胞极化对于形态发生、免疫应答、神经元发育、趋化性和运动性是必不可少的。 酿酒酵母（Saccharomyces cerevisiae）是一种被广泛研究的模式真核生物，它表现出许多极化现象，包括信号诱导的细胞形状和核位置的变化。 在其生命周期的单倍体阶段，酵母细胞分泌肽信息素，将相反交配类型的植物生长细胞转化为配子。 为细胞和核融合做准备，信息素触发朝向交配伴侣的极化生长（向化性），以及核向交配突起的尖端的迁移。 最近的研究结果表明，信息素反应的G-α蛋白，Gpa 1，在信号诱导的极化生长和核运动的控制。 在对信息素作出反应的细胞中，Gpa 1直接与交配特异性MAPK蛋白Fus 3和Kar 3相互作用，Kar 3是一种微管马达蛋白，在交配过程中对核运动至关重要。 Gpa 1-Fus 3相互作用的破坏赋予缺陷的趋化性，微管方向，和核迁移。 该项目的长期目标是了解G α蛋白如何调节微管细胞骨架以响应外部信号。 为此，遗传，生物化学，质谱和成像方法将被用来确定Gpa 1如何影响交配的具体功能的Kar 3，以及是否Fus 3参与这一调节。 因为Gpa 1和Kar 3提供了G α蛋白/运动蛋白相互作用的第一个例子，并且因为G α对核运动的调节是前所未有的，所以这种分析有望提供信息。该项目还将提供重要的培训机会。一名研究生和一名博士后将从事这项研究的几个方面。此外，每年夏天将招募一名高中生参加该项目。