PES-7/IQGAP在内吞循环运输中的调控作用及机制研究

内吞循环运输是生物体内的重要生理过程，负责细胞与外界物质信息交换，其异常会导致诸如神经退行性疾病、II型糖尿病、癌症等疾病发生。然而，学界对于囊泡循环运输调控网络尚有诸多未知。IQGAP参与调控多种生物学过程，在结直肠癌、肺癌、胃癌、乳腺癌等多类型癌组织中高表达，可促进癌细胞侵袭和转移。本项目预研工作发现PES-7/IQGAP是秀丽隐杆线虫极性肠上皮细胞中循环运输的新型调控因子，马达分子肌球蛋白轻链可能与PES-7协同调控循环运输。本项目将系统研究PES-7调控循环运输的功能特异性，阐明PES-7的膜定位及其调控机制，鉴定参与循环运输调控的MLC，辨析PES-7与MLC在循环运输途径中的相关性及其功能机制，并检测该功能在哺乳动物细胞中的保守性及与癌细胞侵袭性的相关性。本项目期望能拓宽学界对循环运输调控网络的理解，为循环运输异常相关癌症的医学干预提供新思路。

Endosomal recycling transport is an important physiological process, responsible for the information exchange between cells and external environment, its defects can cause many diseases such as neurodegenerative diseases, type II diabetes and cancer. However, there are still many unknowns of endosomal recycling transport, and lots of scientific problems need to be solved. IQGAP participates in regulation of multiple biological processes, and is highly expressed in many cancers such as colorectal cancer, lung cancer, gastric cancer, and breast cancer, remarkably, IQGAP aslo can promote cancer cell invasion and metastasis. Our previous work has shown that PES-7 is a new endosomal recycling regulator in C. elegans intestinal epithelial cells, the motor molecule myosin light chain may coordinate with PES-7 to regulate this process. This project will further systematically explore the functional specificity of PES-7 during directing recycling transport, clarify the regulatory mechanism of PES-7 membrane localization, and then identify MLC molecules which one can regulate recycling transport, analyze the correlation between PES-7 and MLC in this pathway , as well as its functional mechanism. Furthermore,we will detect the conservation of this function in mammalian cells and its correlation with cancer cell invasion. This project hopes to broaden academic community's cognition of endosomal recycling regulatory network, and provide new ideas for medical intervention of cancers caused by endosomal recycling defects.