Structural Studies on the Exocyst Tethering Complex

细胞与周围环境之间的物质交换以及细胞间的物质运输对于细胞生长及其与外界的通信至关重要。胞囊是一个约750 kDa的复合物，是质膜分泌囊胞吐所必需的。它是一组大型多聚复合物之一，在转运途径中与协调膜转运事件的Rab GTPases和促进膜融合事件的SNARE蛋白合作起作用。这些“栓系”复合物介导了传入囊泡与其靶膜之间的第一次相互作用，并被认为赋予了膜运输途径的特异性。在这里，为了建立一个框架来理解胞吐的最终事件，我建议从结构上表征异聚胞囊系扣复合物。我将主要使用电子显微镜支持的晶体学技术来阐明完整的囊泡或其他较大的囊泡子组件的结构。对胞囊结构的更详细的了解将大大促进我们对胞囊在胞吐过程中如何发挥作用的理解。

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.