Molecular mechanisms of the GIMAP-5-dependant cell survival pathway in T lymphocytes

T淋巴细胞中GIMAP-5依赖性细胞存活途径的分子机制

• 批准号: 312777-2011
• 负责人: Ramanathan, Sheela
• 金额: $ 2.62万
• 依托单位: Université de Sherbrooke
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=526615
• 关键词: Molecular; mechanisms; GIMAP; dependant; cell

A subset of white blood cells called as 'T cells' are very important to safeguard us from infectious agents such as bacteria and viruses. Under certain circumstances these cells become activated and kill normal tissues leading to autoimmune diseases such as type 1 diabetes and multiple sclerosis. The circulating T lymphocytes survive for long periods of time. Their survival depends on several factors. One of them is a protein called as GIMAP5. In one particular strain of rat called the BB-DP rat the protein GIMAP5 is defective. As a consequence, the T cells in these rats die spontaneously. Therefore these rats cannot protect themselves from infections. GIMAP5 was discovered in 2002 and nothing much is known about its structure or functions. With funding from NSERC, my group showed that GIMAP5 does not function like classical proteins that are involved in cell survival. In this renewal project, I will identify the molecules with which GIMAP5 interacts, understand the mechanisms by which GIMAP5 mediates its survival functions and correlate the function with different part of GIMAP5 protein. Proteins with similar structure are also present in the plants. These proteins protect the plants from certain pathogens. The current project will help in understanding how GIMAP5 and other similar proteins that belong to the family of GIMAP mediate their functions.

一种称为“T细胞”的白色血细胞亚群对保护我们免受细菌和病毒等感染非常重要。在某些情况下，这些细胞被激活并杀死正常组织，导致自身免疫性疾病，如1型糖尿病和多发性硬化症。循环中的T淋巴细胞可以存活很长一段时间。他们的生存取决于几个因素。其中一种蛋白质叫做GIMAP 5。在一种称为BB-DP大鼠的特定大鼠品系中，蛋白质GIMAP 5是有缺陷的。结果，这些大鼠中的T细胞自发死亡。因此，这些老鼠无法保护自己免受感染。GIMAP 5于2002年被发现，但对其结构和功能知之甚少。在NSERC的资助下，我的团队发现GIMAP 5的功能不像参与细胞存活的经典蛋白质。在这个更新项目中，我将鉴定与GIMAP 5相互作用的分子，了解GIMAP 5介导其生存功能的机制，并将其功能与GIMAP 5蛋白的不同部分联系起来。具有类似结构的蛋白质也存在于植物中。这些蛋白质保护植物免受某些病原体的侵害。目前的项目将有助于了解GIMAP 5和其他类似的蛋白质，属于GIMAP家族介导其功能。