Slik as a novel Rho GTPase effector in tissue dynamics and growth

Slik 作为组织动力学和生长中的新型 Rho GTPase 效应器

• 批准号: RGPIN-2017-05819
• 负责人: Hipfner, David
• 金额: $ 1.89万
• 依托单位: Université de Montréal
• 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=711827
• 关键词: Slik; novel; Rho; GTPase; effector

Local communication between cells plays an important role in controlling the normal growth of tissues in embryos. Using the fruit fly as a genetic model organism, we have been studying the role that a protein called Slik plays in such local control of growth. Interestingly, when the levels of Slik in one group of cells in the developing wing of a fly are increased, it stimulates neighbouring cells to divide. We are trying to determine how this works. With a collaborator, we have identified a protein belonging to a class of proteins called GTPases, often implicated in organizing cell structure through a “cytoskeleton” of protein filaments, that binds to Slik in cells. What effect this protein, called Rho1, has on Slik function in growing tissues and vice versa is not known. We propose to use a series of biochemical tests in cells and genetic tests in flies to uncover the importance of the binding of these two proteins, and to use a powerful new technique for identifying interacting proteins in cells to find other proteins that bind Slik and may be important for its function. Because humans also have Slik and Rho1-like proteins, our work in flies will provide important insights into one of the mechanisms controlling tissue growth in us.

细胞之间的局部通讯在控制胚胎组织的正常生长中起着重要作用。利用果蝇作为遗传模式生物，我们一直在研究一种名为Slik的蛋白质在这种局部控制生长中的作用。有趣的是，当果蝇翅膀发育中的一组细胞中的Slik水平增加时，它会刺激邻近的细胞分裂。我们正在试图确定这是如何工作的。与合作者一起，我们已经确定了一种属于一类称为GTP酶的蛋白质的蛋白质，通常涉及通过蛋白质细丝的“细胞骨架”组织细胞结构，该蛋白质与细胞中的Slik结合。这种名为Rho1的蛋白质对生长组织中的Slik功能有什么影响，反之亦然，目前尚不清楚。我们建议在细胞中使用一系列生化测试和在苍蝇中进行遗传测试，以揭示这两种蛋白质结合的重要性，并使用一种强大的新技术来识别细胞中相互作用的蛋白质，以找到其他结合Slik的蛋白质，并可能对其功能很重要。由于人类也有Slik和Rho1样蛋白，我们在苍蝇中的工作将为控制我们组织生长的机制之一提供重要的见解。