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Novel effectors of multivesicular body sorting

多泡体分选的新型效应器

基本信息

批准号：
BB/I012109/1
负责人：
Philip Woodman
金额：
$ 43.56万
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：
2011
资助国家：
英国
起止时间：
2011 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FI012109%2F1
关键词：
Novel effectors multivesicular body sorting

项目摘要

The behaviour of cells within a tissue is controlled by their environment. Amongst the most important signals that cells receive are from circulating small proteins called growth factors. These bind to specific proteins, called 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 so-called mitogenic responses, which enable cells to grow and divide. In order to prevent these responses continuing endlessly, which would lead to uncontrolled cell division, the growth factor receptor must be sent to an environment where it can no longer communicate with other cellular contents. Ultimately, it is sent to a specialised compartment within the cell, called the lysosome, where it is destroyed. Movement, or trafficking, 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 first move to and coalesce with an intermediate compartment called the endosome, which is rather like a balloon. Importantly, the growth factor receptors are still active when they reach the endosome. To ensure they are stopped from working, they are enclosed within little vesicles that are forced within the inside of the endosome. This occurs by a process of inward budding, rather like poking deep impressions into a balloon and imagining these could pinch off to form internal packets. This process means that the mitogenic receptors are now completely separated away from the rest of the cell contents and unable to work. The endosome, along with these internal packages, is then sent to the lysosome. The aim of this project is to understand how activated mitogenic receptors, once they reach the endosome, are packaged into the interior of the compartment. The project will focus on identifying the function of a new protein involved in this process, and ask how delivery of new vesicles to the endosome is coupled to the formation of internal vesicles, so the whole process of receptor inactivation works with maximum efficiency.

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来自循环中的小蛋白质，称为生长因子。它们与细胞表面的特定蛋白质（称为受体）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。通过这种方式，生长因子受体作为细胞外部和内部之间的重要桥梁，刺激所谓的促有丝分裂反应，使细胞能够生长和分裂。为了防止这些反应无休止地继续下去，这将导致不受控制的细胞分裂，生长因子受体必须被送到一个环境，在那里它不能再与其他细胞内容物通信。最终，它被送到细胞内的一个专门的隔间，称为溶酶体，在那里它被破坏。受体从细胞表面到溶酶体的移动或运输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。这些囊泡首先移动到一个叫做内体的中间室并与之结合，内体很像气球。重要的是，生长因子受体在到达内体时仍然是活性的。为了确保它们停止工作，它们被封闭在小泡内，这些小泡被迫进入内体内部。这是通过一个向内发芽的过程发生的，就像把深深的印象戳进气球里，想象这些印象可以收缩形成内部的包。这个过程意味着促有丝分裂受体现在完全与细胞内容物的其余部分分离，并且无法工作。内体，沿着这些内部包装，然后被送到溶酶体。这个项目的目的是了解激活的促有丝分裂受体，一旦它们到达内体，是如何包装到隔间的内部。该项目将专注于确定参与这一过程的新蛋白质的功能，并询问如何将新囊泡递送到内体与内部囊泡的形成相结合，从而使受体失活的整个过程以最高效率工作。