Heterotrimeric G Protein Regulation of Chemotropism in Yeast

趋化性，或响应于化学引诱剂或驱避剂的化学梯度的定向细胞运动，在发育和免疫中起着至关重要的作用。向化性（响应化学梯度的定向细胞生长）的相关现象是神经系统发育、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和动态的。细胞是如何利用这些微妙的线索进行导航的？趋化现象的模型引起正反馈回路，其将跨细胞表面的受体活化的微小差异放大成实质上更陡的细胞内信号梯度。据推测，趋化性细胞的反应浅的化学梯度也被放大的相互作用的反馈回路，但这样的回路缺乏一个机械的理解。芽殖酵母酿酒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，并使它们向最接近的伴侣的方向生长。梯度感应依赖于一种叫做信息素受体的表面蛋白和一种叫做G γ的相关蛋白。在信息素刺激受体后，Ggamma启动许多蛋白质组装成所谓的趋化复合物，该复合物催化细胞在适当部位的生长。目前尚不清楚细胞如何感知方向并正确定位生长部位，该项目的目标是了解酵母细胞如何启动朝向交配伴侣的定向生长。这项调查将提供一个机制的理解，Ggamma磷酸化在酵母趋化反应中发挥的作用。由于鲜为人知的是定向传感在其他真核生物的趋化性反应，一般原则很可能会出现从这项工作，将广泛影响研究的趋化性phenomenon.Broader ImpactsThe PI率先发展，现在正在管理的NSF/顶点本科生研究计划的荣誉学生主修生物科学在伊利诺伊大学芝加哥。学生与导师配对进行一个学期的阅读，然后进行四个学期的研究，在年度NSF/Capstone小型研讨会上正式介绍他们的工作。至少有两名NSF/Capstone学生将在本项目的学年和夏季在PI的实验室工作。该项目博士后研究员的培训计划包括学习本研究所需的分子遗传学和成像方法，指导本科生和研究生的生物化学方法，讲授研究生水平的信号转导课程，举办年度部门研讨会，以及开发和资助自己的独立研究计划。受训人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，在国外进行研究。

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.