中文摘要
溶酶体是细胞内物质降解的主要场所,在细胞的生长、代谢、分化、稳态维持及功能执行等方面起着至关重要的作用。溶酶体的降解的底物来源于细胞外部或内部,通过内吞体-溶酶体、吞噬体-溶酶体或自噬体-溶酶体等运输方式而使各种底物运送到溶酶体被降解。小GTP酶Rab7在这些过程中发挥关键作用。Rab7的功能是通过与其特异的效应蛋白之间的互作而实现的。我们前期工作发现一个含 WD40 重复的蛋白--WDR91是Rab7的一个新效应因子,但它在溶酶体运输通路中的功能和作用机制不得而知。本项目中,我们将深入研究WDR91与Rab7的相互作用在内吞体-溶酶体、吞噬体-溶酶体和自噬体-溶酶体运输及信号传递等方面的功能,揭示WDR91对组织和器官发育的影响。
英文摘要
The lysosome is central to cell growth, differentiation, metabolism and homeostasis by degrading a wide variety of extra- and intra-cellular cargoes. Cargoes resulting from endocytosis, phagocytosis, or autophagy are delivered to lysosomes through endosome-lysosome, phagosome-lysosome, or autophagosome-lysosome pathways, in which the Rab7 small GTPase plays a central role. The function of Rab7 is achieved largely by interacting with diverse effector proteins. Our preliminary studies have identified WDR91, a WD40 repeat-containing protein as a novel effector of Rab7, but its function and regulatory mechanisms remain unknown. In this project, we propose to carry out in-depth investigation to elucidate the role of WDR91 in lysosomal trafficking and to understand how it affects tissue and organ development.
