How is vesicle uncoating achieved? Dissecting early events in clathrin disassembly by the molecular chaperone, Hsc70

细胞利用囊泡的运动作为许多重要化合物的主要运输系统。这种运输方式被称为内吞和囊泡运输。物质通过内吞作用进入细胞，在此过程中，由细胞膜形成囊泡，囊泡包围特定分子。在形成的囊泡周围需要专门的蛋白质外壳，这有助于选择内容物，并指导形成和分离的时间和地点。被膜以精确控制的方式在囊泡上组装和拆卸，这对细胞的正确功能至关重要。我们希望从分子水平上详细研究囊泡的外壳是如何被去除的，以及哪些事件对于触发这种脱膜事件是重要的。我们将使用一系列不同的物理方法来观察哪些蛋白质在哪个时间点结合，以及它们的形状是否在脱壳过程中发生变化。我们还将使用特殊的突变形式的Hsc 70，它只执行某些步骤沿着这一途径，剖析出这些步骤的顺序和它们的重要性，在脱壳。因此，这些研究将产生一个图像的启动脱壳囊泡外套，让我们看到这个有趣的分子机器是如何工作的。

Cells use the movement of vesicles as their primary transport system for many important compounds. This method of transportation is termed endocytosis and vesicle trafficking . Substances are brought into the cell via endocytosis, during which a vesicle is formed from the cell membrane which encloses specific molecules. A specialised protein coat is required around the forming vesicle which helps select the contents and also directs the time and place of formation and detachment. The coat assembles and disassembles on the vesicle in a precisely controlled manner which is vital to the correct functioning of the cell. We wish to study in molecular detail how the coat is removed from the vesicle and what events are important for triggering this uncoating event. We will use a range of different physical methods to see which proteins bind at which point in time and whether their shape alters during uncoating. We will also use special mutant forms of Hsc70 which only perform certain steps along this pathway to dissect out the order of these steps and their importance in uncoating. Hence these studies will produce a picture of the initiation of uncoating of the vesicle coat and allow us to see how this intriguing molecular machine works.