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.

趋化性或响应于化学吸引剂或驱虫剂的化学梯度的定向细胞运动在发育和免疫力中起着至关重要的作用。趋化性现象（响应化学梯度的定向细胞生长）是神经系统发展，血管发育，植物授粉和真菌感染的组成部分。天然发生的化学梯度非常浅和动态。细胞如何使用如此微妙的提示导航？趋化现象的模型引起了正反馈回路，这些反馈会扩大细胞表面受体激活的微小差异，使细胞内信号传导梯度更加陡峭。假定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放大，但是缺乏对这种环的机械理解。酿酒酵母的萌芽酵母菌的交配反应是趋化的：交配细胞解释了复杂的信息素梯度，并在最接近伴侣的方向上偏振它们的生长。梯度传感取决于称为信息素受体的表面蛋白，也取决于称为ggamma的相关蛋白。在对受体刺激的信息素刺激后，Ggamma将许多蛋白质组装到所谓的趋化复合物中，该复合物在适当的位点催化细胞的生长。尚不清楚细胞如何感官方向并正确地定向生长位点，而该项目的目的是了解酵母细胞如何启动对交配伴侣的方向生长。这项研究将提供对Ggamma磷酸化在酵母趋化反应中起作用的作用的机械理解。由于对其他真核生物的趋化反应中的方向感应知之甚少，因此从这项工作中可能出现一般原则，这将广泛影响趋化现象的研究。Broader对PI的发展影响了PI的发展，并且现在正在为NSF/Capstone少年研究对荣誉学业的研究专业的学生专业的学生掌管研究。学生与一位学期的导师配对，然后进行四个学期的研究，从而正式在NSF/Capstone Mini-Symposium上对工作进行正式介绍。在该项目期间，至少有两个NSF/Capstone学生将在PI的实验室和夏季工作。该项目的博士后研究员的培训计划包括学习本研究中所需的分子遗传和成像方法，指导本科生和研究生生化方法，在研究生水平的信号转导课程中讲授，展示年度部门研讨会，并提供和发展和资助自己独立的研究计划。学员将有机会通过与该项目的合作者罗伯特·阿科维茨（Robert Arkowitz）（法国尼斯大学）合作进行国外研究。