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

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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.