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，免疫反应，神经元发育，趋化性和运动至关重要。 酿酒酵母是一种经过良好研究的模型真核生物，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。 在生命周期的单倍体阶段，酵母细胞分泌肽信息素，这些信息素将相反类型的营养细胞转化为配子。 在细胞和核融合中准备，信息素触发了对交配伴侣（趋化伴侣）的极化生长，并将细胞核迁移到交配投影的尖端。 最近的结果暗示，信息素反应性G-α蛋白GPA1在控制信号诱导的极化生长和核运动方面。 在对信息素反应的细胞中，GPA1直接与交配特异性MAPK蛋白FUS3相互作用，而Kar3是一种微管运动蛋白，这对于配合过程中的核运动至关重要。 GPA1-FUS3相互作用的破坏赋予了趋化性，微管取向和核迁移的缺陷。 该项目的长期目标是了解Gα蛋白如何根据外部信号响应微管细胞骨架调节微管细胞骨架。 为此，将使用遗传，生化，质谱和成像方法来确定GPA1如何影响KAR3的交配功能，以及FUS3是否参与了该调节。 因为GPA1和KAR3提供了Gα蛋白/运动蛋白相互作用的第一个例子，并且由于核运动的Gα调节是没有前所未有的，因此该分析有望提供信息。该项目还将提供大量的培训机会。研究生和博士后研究员将研究研究的几个方面。此外，每年夏天将招募一名高中生参加该项目。