Analyzing the role of the Ras effector TJ1 in controlling chemotaxis in Dictyostelium discoideum

分析Ras效应子TJ1在控制盘基网柄菌趋化性中的作用

• 批准号: 41857516
• 负责人: Dr. Verena Kölsch
• 金额: --
• 依托单位: Institut für Zellbiologie
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/41857516?language=en
• 关键词: Analyzing; role; Ras; effector; TJ1

Chemotaxis plays a central role in various biological processes such as cellular morphogenesis, innate immunity, inflammation, and metastasis of cancer cells. Cells respond to shallow extracellular gradients which become highly amplified intracellularly via the localized activation of Ras, Rap1, and PI3K resulting in F-actin polymerization at the leading edge. Ras is an important upstream activator of chemoattractant-mediated PI3K activity; however, genetic data indicate that there must be other Ras effectors regulating chemotaxis. The Firtel lab recently identified a new Ras effector TJ1, a member of the MRL (Mig10/RIAM/Lpd) family of adaptor proteins, which they have shown is required for proper chemotaxis. Through the use of cell biological and molecular genetic approaches, I propose to dissect the function and regulation of TJ1, to obtain greater insight into how Ras signalling controls chemotaxis. I will use biochemical approaches to identify the binding partners of TJ1 and employ mutational studies to dissect how TJ1 is regulated and functions. In addition, I will examine the role of TJ1 and Ras signalling in controlling the vectors of the forces that control cell movement.

趋化性在细胞形态发生、先天免疫、炎症和癌细胞转移等多种生物学过程中起着重要作用。细胞响应于浅的细胞外梯度，其通过Ras、Rap 1和PI 3 K的局部活化在细胞内高度扩增，导致前沿的F-肌动蛋白聚合。Ras是化学引诱剂介导的PI 3 K活性的重要上游激活剂;然而，遗传数据表明必须有其他Ras效应物调节趋化性。Firtel实验室最近发现了一种新的Ras效应器TJ 1，它是MRL（Mig 10/RIAM/Lpd）衔接蛋白家族的成员，他们已经证明这是适当趋化性所必需的。通过使用细胞生物学和分子遗传学的方法，我建议剖析TJ 1的功能和调节，以获得更深入的了解Ras信号如何控制趋化性。我将使用生物化学的方法来确定TJ 1的结合伙伴，并采用突变研究来剖析TJ 1是如何调节和功能。此外，我将研究TJ 1和Ras信号在控制细胞运动的力的载体中的作用。