Structural Studies on the Exocyst Tethering Complex

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The exchange of material between the cell and the surrounding environment as well as the transport of substances between cellular compartments are essential for cell growth and the communication with its exterior. The exocyst is a ~750 kDa complex that is required for exocytosis of secretory vesicles at the plasma membrane. It is one of a group of large multimeric complexes that function late in trafficking pathways in cooperation with Rab GTPases, which coordinate membrane trafficking events, and the SNARE proteins, which facilitate the membrane fusion events. These “tethering” complexes mediate the first interaction between incoming vesicle and its target membrane and are thought to confer specificity to membrane trafficking pathways. Here, to lay a framework for understanding the final events in exocytosis, I propose to structurally characterize the heterooctameric exocyst tethering complex. I will use primarily crystallographic techniques supported by electron microscopy to elucidate the structure of either the intact exocyst or else larger exocyst subassemblies. A more detailed knowledge of exocyst architecture will significantly advance our understanding how the exocyst functions in bringing about exocytosis.