Novel effectors of multivesicular body sorting

组织中细胞的行为受其所处环境的控制。细胞接收到的最重要的信号之一是来自循环中的小蛋白质——生长因子。它们与特定的蛋白质结合，这种蛋白质被称为受体，存在于细胞表面。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相互作用的模式。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，刺激所谓的有丝分裂反应，使细胞生长和分裂。为了防止这些反应无休止地持续下去，从而导致不受控制的细胞分裂，生长因子受体必须被送到一个不能再与其他细胞内容物交流的环境中。最终，它被送到细胞内一个叫做溶酶体的特殊隔间，在那里被破坏。受体从细胞表面到溶酶体的运动或运输涉及到受体被隔离在细胞表面膜的区域中，这些区域内陷并挤压形成细胞内部的球形包或囊泡。这些囊泡首先移动到一个叫做核内体的中间腔室并与之结合，核内体很像一个气球。重要的是，当生长因子受体到达核内体时，它们仍然是活跃的。为了确保它们停止工作，它们被封闭在小囊泡中，这些小囊泡被强制进入核内体内部。这是通过向内萌芽的过程发生的，就像在气球上戳一个很深的印子，想象这些印子可以捏掉形成内部的包。这一过程意味着有丝分裂受体现在与细胞内容物的其余部分完全分离，无法工作。核内体和这些内部包裹体一起被送到溶酶体。这个项目的目的是了解激活的有丝分裂受体，一旦它们到达核内体，是如何被包装到隔室的内部的。该项目将重点确定参与这一过程的新蛋白质的功能，并研究如何将新囊泡输送到核内体与内部囊泡的形成相耦合，从而使整个受体失活过程以最大效率进行。

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.