Regulation of Rho-GTPase pathways by the adaptor protein, Dok-4

接头蛋白 Dok-4 对 Rho-GTPase 通路的调节

• 批准号: RGPIN-2018-04599
• 负责人: Takano, Tomoko
• 金额: $ 2.62万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=713162
• 关键词: Regulation; Rho; GTPase; pathways; adaptor

Epithelial cells are lining the walls of important structures in body organs such as lungs, intestines and the kidney. Our laboratory studies how the epithelial cells work, specifically focusing on the kidney. In response to injury, growth factors produced naturally in the kidney help the damaged epithelial cells to regenerate, in part by promoting the capacity of cells to divide and increase in numbers to replace dead cells. However, these newly regenerated cells need to regain sophisticated structure by the process called differentiation in order to restore their normal functions. We propose that a molecule called Dok-4 will help balance various regulators of the cell structure thereby contributing to the differentiation of epithelial cells. In this study, we will examine how Dok-4 is turned on at a certain stage of epithelial cell recovery and switches off one regulatory protein while switches on another regulatory protein of an opposing function. We expect that Dok-4 will act as a critical molecular switch which will direct the cells toward full recovery of function after an injury.

上皮细胞排列在身体器官如肺、肠和肾的重要结构的壁上。我们的实验室研究上皮细胞是如何工作的，特别关注肾脏。在对损伤的反应中，肾脏中自然产生的生长因子帮助受损的上皮细胞再生，部分是通过促进细胞分裂的能力和增加数量来取代死亡细胞。然而，这些新再生的细胞需要通过称为分化的过程重新获得复杂的结构，以恢复其正常功能。我们提出，一种名为Dok-4的分子将有助于平衡细胞结构的各种调节因子，从而有助于上皮细胞的分化。在这项研究中，我们将研究Dok-4如何在上皮细胞恢复的某个阶段打开，并关闭一种调节蛋白，同时打开另一种相反功能的调节蛋白。我们预计Dok-4将作为一个关键的分子开关，指导细胞在损伤后完全恢复功能。