CHW-1/RhoU/RhoV作为潜在微丝稳态调控因子在循环运输中的功能研究

细胞内持续动态变化的微丝网络对于内吞循环运输的有序运行至关重要。研究表明，分枝状和线性微丝结构间存在动态平衡，但不同架构的微丝结构间稳态维持在循环运输过程中的功能意义尚不明晰。我们的前期工作发现，非传统Rho家族蛋白CHW-1/RhoU/RhoV参与介导非网格蛋白依赖内吞（CIE）膜蛋白的循环运输，CHW-1缺失细胞中循环膜蛋白异常累积，微丝结构显著增加，且VIRO-2/WASP/N-WASP 是潜在的CHW-1效应因子。本项目拟运用整体动物研究手段确定CHW-1调控CIE循环运输特异性、亚细胞定位及遗传学功能位置，分析CHW-1调控微丝聚合组装的分子机制，探讨CHW-1对微丝结构间动态平衡调控的方向性，解析CHW-1在微丝结构稳态调控循环运输过程中的功能角色。本项目将丰富对微丝结构动态平衡机制的认识，加深对微丝结构稳态与循环运输之间功能联系的理解。

Continuously adapting F-actin networks are essential for efficient endocytic recycling. Previous studies have shown that there is a dynamic balance between branched actin and linear actin systems. However, the functional significance of maintaining the steady-state between actin structures of distinct architecture during endocytic recycling is still mostly unknown. Our preliminary study observed that non-canonical Rho family protein CHW-1/RhoU/RhoV is involved in the recycling of clathrin-independent endocytic (CIE) cargo protein. Loss of CHW-1 leads to abnormal accumulation of cargo proteins in the cytoplasm and a noticeable increase of actin structures. Moreover, VIRO-2/WASP/N-WASP acts as a potential CHW-1 effector. In the current study, we will use the whole animal system to determine the regulatory specificity, subcellular localization, and genetic position of CHW-1. Moreover, we will dissect the underlying mechanism of CHW-1 in directing the assembly of actin filaments, examine the regulatory directionality of CHW-1 on the dynamic balance between actin structures, and probe the functional role of CHW-1 in the process of recycling regulation by actin homeostasis administration. The implementation of this research will improve the understanding of actin dynamic balance maintenance, and expand the knowledge of the functional relationship between actin structures homeostasis and endocytic recycling.