Heterotrimeric G Protein Regulation of Chemotropism in Yeast

异源三聚体 G 蛋白对酵母趋化性的调节

• 批准号: 1024718
• 负责人: David Stone
• 金额: $ 91.43万
• 依托单位: University of Illinois at Chicago
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1024718&HistoricalAwards=false
• 关键词: Heterotrimeric; Protein; Regulation; Chemotropism; Yeast

Chemotaxis, or directed cell movement in response to a chemical gradient of a chemoattractant or repellent, plays a vital role in development and immunity. The related phenomenon of chemotropism (directed cell growth in response to a chemical gradient) is integral to the development of the nervous system, blood vessel development, plant pollination and fungal infection. Naturally occurring chemical gradients are very shallow and dynamic. How do cells navigate using such subtle cues? Models of chemotactic phenomena invoke positive feedback loops that amplify small differences in receptor activation across the cell surface into a substantially steeper intracellular signaling gradient. It is presumed that the response of chemotropic cells to shallow chemical gradients is also amplified by interacting feedback loops, but a mechanistic understanding of such loops is lacking. The mating response of the budding yeast Saccharomyces cerevisiae is chemotropic: mating cells interpret complex pheromone gradients and polarize their growth in the direction of the closest partner. Gradient sensing depends on both a surface protein called the pheromone receptor, and an associated protein called Ggamma. Upon pheromone stimulation of the receptor, Ggamma initiates the assembly of numerous proteins into what is known as the chemotropic complex, which catalyzes growth of the cell at the appropriate site. It is not known how the cell senses direction and correctly orients the growth site, and the goal of this project is to understand how yeast cells initiate directional growth toward a mating partner. This investigation will provide a mechanistic understanding of the role that Ggamma phosphorylation plays in the yeast chemotropic response. Because little is known about directional sensing during the chemotropic responses of other eukaryotes, general principles are likely to emerge from this work that will broadly influence the study of chemotropic phenomena.Broader ImpactsThe PI spearheaded the development of and is now administering the NSF/Capstone Undergraduate Research Program for honors students majoring in Biological Sciences at the University of Illinois at Chicago. Students are paired with a mentor for a semester of reading followed by four semesters of research leading to a formal presentation of their work at the annual NSF/Capstone mini-symposium. A minimum of two NSF/Capstone students will work in the PI's lab during the academic year and summertime during this project. The training plan for the postdoctoral fellow on the project includes learning the molecular genetic and imaging methods required in this investigation, mentoring undergraduate and graduate students in biochemical approaches, lecturing in a graduate level signal transduction course, presenting an annual departmental seminar, and developing and funding their own independent research program. Trainees will have an opportunity to undertake research abroad, through collaboration with Dr. Robert Arkowitz (University of Nice, France), a collaborator in this project.

趋化性，即细胞在化学引诱剂或驱避剂的化学梯度下的定向运动，在发育和免疫中起着至关重要的作用。相关的趋化现象（根据化学梯度定向细胞生长）是神经系统发育、血管发育、植物授粉和真菌感染的组成部分。自然发生的化学梯度是非常浅的和动态的。细胞是如何利用这些微妙的线索进行导航的呢？趋化现象的模型调用了正反馈回路，将细胞表面受体激活的微小差异放大为一个实质上更陡峭的细胞内信号梯度。据推测，趋化细胞对浅化学梯度的反应也通过相互作用的反馈回路被放大，但缺乏对这种回路的机制理解。出芽酵母的交配反应是趋化性的：交配细胞解释复杂的信息素梯度，并向最接近的伴侣方向极化生长。梯度感应依赖于一种叫做信息素受体的表面蛋白质和一种叫做伽马的相关蛋白质。在信息素对受体的刺激下，伽马启动了许多蛋白质的组装，形成了所谓的趋化复合物，它催化了细胞在适当部位的生长。目前尚不清楚细胞是如何感知方向并正确定位生长部位的，而这个项目的目标是了解酵母细胞是如何启动朝向交配伴侣的定向生长的。这项研究将为酵母趋化反应中伽马磷酸化的作用提供一个机制的理解。由于对其他真核生物在趋化反应过程中的定向传感知之甚少，因此这项工作可能会产生一般原理，这将广泛影响趋化现象的研究。更广泛的影响PI是美国国家科学基金会/凯普斯通本科生研究项目的牵头人，该项目面向伊利诺伊大学芝加哥分校生物科学专业的荣誉学生。学生将与导师一起进行一个学期的阅读，然后进行四个学期的研究，最终在年度NSF/Capstone小型研讨会上正式展示他们的工作。至少有两名NSF/Capstone学生将在学年和夏季期间在PI的实验室工作。该项目的博士后培养计划包括学习本次调查所需的分子遗传学和成像方法，指导本科生和研究生的生化方法，在研究生水平的信号转导课程上授课，在年度部门研讨会上发表演讲，并制定和资助自己的独立研究计划。学员将有机会与该项目的合作者Robert Arkowitz博士（法国尼斯大学）合作，到国外进行研究。