Defining factors that ensure unidirectionality of endocytosis

细胞是生命的基本单位，所有生物体都是由一个或多个细胞组成的。这些细胞被嵌入在细胞表面的蛋白质所覆盖。这种蛋白质外壳帮助细胞执行某些功能，比如对化学信息做出反应。这种外衣也能让其他细胞识别它。一个类比是根据人们穿的衣服来识别不同的人群。然而，有时细胞接收到的信息会告诉它采取不同的行动。因此，它需要去除其蛋白质外壳的元素。许多细胞做到这一点的方法之一是内化一些来自被毛的蛋白质。这种蛋白质的内化是通过一个叫做内吞作用的过程来实现的。细胞表面向内折叠成小块，然后在细胞内部被挤压掉。这就形成了一个小泡，可以将蛋白质携带到细胞内。通常这些蛋白质会被分解，它们最基本的部分会被释放出来供细胞重新利用。这样，涂层中不需要的部分就可以去掉了。与此同时，这个过程通常通过向细胞表面添加新的蛋白质来平衡，这些蛋白质对不同的信息作出反应。如果由于内吞作用不正常而导致蛋白质不能被正确移除，细胞表面可能会有蛋白质传递相互矛盾的信息，这可能对细胞的健康有害。一些疾病与缺陷内吞作用有关，包括阿尔茨海默病、亨廷顿舞蹈症和癌症。此外，一些病原体和毒素利用内吞途径进入细胞。该项目旨在使用一个简单的系统来了解细胞如何从其表面吸收蛋白质。我们使用一种叫做酵母的模式生物，因为参与内吞过程的分子与更复杂的人类细胞中的分子非常相似，但酵母细胞更容易操纵，以研究我们感兴趣的过程。特别是，我们正在努力确定机制，以确保一旦内部化进程开始，它就会继续完成。我们知道内吞过程涉及50多种蛋白质。它们中的许多相互形成基团或复合物，然后这些基团的组成部分与一个称为Las17/WASP的单一因子相互作用。我们的目标是测试这种特殊蛋白质在内吞过程中起棘轮作用的想法。通过密切调节这一蛋白质的相互作用，细胞可以确保相互作用顺序发生。总的来说，我们认为这可能是确保内吞作用的关键阶段以线性方式进行的机制，而不是在内陷完成和膜在细胞内挤压之前开始然后逆转或流产。我们将在细胞内外使用广泛的技术来研究Las17/WASP的相互作用，并确定这些相互作用是如何被调节以确保内吞作用正确发挥作用的。

Cells are the basic unit of life and all organisms are composed of one or more cells. These cells are covered in proteins that are embedded in their cell surface. This protein coat helps cells to perform certain functions such as responding to chemical messages. The coat also lets other cells recognise it. An analogy would be recognising groups of people according to the clothes they wear. However, sometimes a message that a cell receives tells it to behave differently. It therefore needs to remove elements of its protein coat. One of the ways that many cells do this is by a process of internalising some of the proteins from the coat. This protein internalisation is achieved by a process called endocytosis. The surface of the cell folds inwards in small portions and then pinches off inside the cell. This forms a small vesicle that can then carry the protein away inside the cell. Often the proteins get broken down and their most basic parts are released for re-use by the cell. In this way the parts of the coat that are not needed can be removed. At the same time, this process is often balanced by the addition of new proteins, which respond to different messages, to the cell surface. If the proteins are not removed properly because endocytosis is not functioning correctly, the cell could have proteins at the surface that send conflicting messages that may be detrimental to the well-being of the cell. Several diseases have been associated with defective endocytosis including Alzheimers, Huntingtons and cancer. In addition, several pathogens and toxins exploit the endocytic pathway to gain entry to cells. This project aims to use a simple system to understand how cells can take-up proteins from their surface. We are using a model organism called yeast because the molecules involved in the endocytic process are very similar to those in more complex human cells, but the yeast cells are much easier to manipulate to investigate the processes we are interested in. In particular we are trying to determine the mechanisms that ensure that once the internalisation process has begun, that it continues to completion. We know that the endocytosis process involves more than 50 proteins. Many of them form groups or complexes with one another, and then components of these groups interact with a single factor that is called Las17/WASP. We aim to test the idea that this particular protein acts as a ratchet in the endocytic process. By closely regulating the interactions of this one protein, the cell can ensure that interactions take place sequentially. Overall, we think that this might be the mechanism that ensures key stages of endocytosis proceed in a linear fashion rather than starting and then reversing or aborting before the invagination has completed and the membrane has pinched off inside the cell. We will use a wide range of techniques both inside and outside of the cell environment to investigate the interactions of Las17/WASP and to determine how these interactions are regulated to ensure endocytosis functions correctly.