Rab proteins, microtubule motors and the organisation of the endocytic pathway

Rab 蛋白、微管马达和内吞途径的组织

• 批准号: G0600253/1
• 负责人: Philip Woodman
• 金额: $ 42.23万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0600253%2F1
• 关键词: Rab; proteins; microtubule; motors; organisation

The behaviour of cells within a tissue is controlled by their environment. Amongst the most important signals that cells receive are in the form of circulating small proteins called growth factors. These bind to specific receptors that are found on the surface of cells. Binding of growth factors causes the receptors to alter their pattern of interactions with many molecules inside the cell that control cell growth. In this way growth factor receptors act as essential bridges between the cell exterior and interior to stimulate proliferative, or mitogenic responses. In order to prevent such mitogenic responses continuing endlessly, which would lead to uncontrolled cell division, the growth factor receptor must be inactivated shortly after the growth factor binds. This is achieved by removing the activated receptor from the cell surface and sending it to a specialised compartment within the cell, where it can be degraded. This compartment is called the lysosome. Movement of the receptor from the cell surface to the lysosome involves the receptor being sequestered into regions of the cell surface membrane that invaginate and pinch off to form spherical packages, or vesicles, within the cell interior. These vesicles move in a directed fashion to the lysosome, via a number of intermediate compartments. The situation becomes more complicated when it is realised that the route that growth factor receptors take to the lysosome is also followed part of the way by other types of receptor, which are engaged in taking up nutrients. These receptors are returned to the cell surface from the intermediate compartments so that they can participate in further rounds of nutrient uptake. Hence, at a critical point along the pathway towards the lysosome, these receptors are selected away. The aim of this project is to understand how this diversion takes place.

组织内细胞的行为受其环境控制。细胞接收的最重要的信号是循环的小蛋白质，称为生长因子。它们与细胞表面的特定受体结合。生长因子的结合导致受体改变其与细胞内控制细胞生长的许多分子的相互作用模式。以这种方式，生长因子受体作为细胞外部和内部之间的重要桥梁，以刺激增殖或促有丝分裂反应。为了防止这样的促有丝分裂反应无休止地持续，这将导致不受控制的细胞分裂，生长因子受体必须在生长因子结合后不久失活。这是通过从细胞表面去除活化的受体并将其发送到细胞内的专门区室来实现的，在那里它可以被降解。这个区室被称为溶酶体。受体从细胞表面到溶酶体的移动涉及受体被隔离到细胞表面膜的区域中，这些区域内陷并夹断以在细胞内部形成球形包装或囊泡。这些囊泡通过许多中间隔室以定向方式移动到溶酶体。当人们意识到生长因子受体进入溶酶体的路线也被其他类型的受体部分遵循时，情况变得更加复杂，这些受体参与摄取营养物质。这些受体从中间区室返回到细胞表面，以便它们可以参与进一步的营养摄取。因此，在通向溶酶体的途径的沿着的临界点，这些受体被选择走。本项目的目的是了解这种转移是如何发生的。