MINORITY PREDOCTORAL FELLOWSHIP PROGRAM

描述（由申请人提供）：反式高尔基网络（TGN）和核内体是分类和运输各种生物合成和内吞蛋白的主要位点，包括参与胆固醇稳态、病毒感染和细胞生长调节的因子。TGN和核内体之间的蛋白质运输是通过囊泡进行的，囊泡被主要由网格蛋白和接头AP-1和Gga组成的外壳包围。虽然这些关键的外壳成分已经被很好地研究过，但我们对调节网格蛋白介导的TGN和核内体之间运输所需的辅助因子的了解还不完整。本研究将描述一种进化上保守的被认为是酿酒酵母的网格蛋白辅助蛋白，它似乎在AP-1介导的运输中特异性地起作用。它在蛋白质运输中的功能和作用将通过检查缺乏蛋白质的细胞中网格蛋白介导的运输来解决，其他辅助因子将在结合伴侣的筛选中确定。这些研究将促进我们对TGN和核内体之间蛋白质转运机制的理解，并有助于区分目前尚未解决的AP-1和gga介导的途径。

DESCRIPTION (provided by applicant): The trans-Golgi network (TGN) and endosomes are major sites for sorting and trafficking of a variety of biosynthetic and endocytic proteins, including factors that are involved in cholesterol homeostasis, virus infection, and cell growth regulation. Protein transport between the TGN and endosomes occurs via vesicles surrounded by coats composed mainly of clathrin and the adaptors AP-1 and Gga. Though these key coat components have been well-studied, our knowledge about accessory factors that are needed to regulate clathrin-mediated transport between the TGN and endosomes is less complete. This study will characterize an evolutionarily conserved putative clathrin accessory protein of Saccharomyces cerevisiae that appears to act specifically in AP-1 mediated transport. Its function and role in protein trafficking will be addressed by examining clathrin-mediated transport in cells lacking the protein and additional accessory factors will be identified in screens for binding partners. These studies will advance our understanding of the mechanisms of protein transport between the TGN and endosomes and help distinguish between the currently unresolved AP-1 and Gga-mediated pathways.