内吞循环运输介导细胞与外界的物质信息交换，对细胞生命活动的有序运行至关重要。微丝结构动态变化在循环运输过程中必不可少，作为运输轨道和动力来源参与膜形变、膜出芽等过程，但学界对微丝动态调控机制仍缺乏了解。通过前期筛选和初步研究，我们发现RTKN-1/Rhotekin以独立于Rho家族蛋白的方式参与调控循环运输，RTKN-1缺失细胞中微丝结构大量减少，但RTKN-1本身并不影响微丝的聚合、解聚效率。本课题将研究RTKN-1的亚细胞定位机制及膜蛋白调控特异性，阐明RTKN-1与UNC-60A/cofilin、LEV-11/tropomyosin的功能关系，解析RTKN-1介导的微丝动态在循环调控中的功能意义，并进一步探讨Rhotekin的循环调控功能保守性及其与多类型癌细胞增殖侵袭的相关性。本研究期望能加深对循环运输过程中微丝动态调控的认知，为循环运输异常相关癌症的治疗提供基础科学依据。

Endocytic recycling mediates the exchange of macromolecules and fluid between the extracellular environment and the cell, which is essential for diverse biological processes. Previous studies have revealed that actin dynamics provides the mechanical force for the endosome transformation, budding, fission, and moving, but the precise mechanism remains obscure. Our preliminary investigation found that RTKN-1/Rhotekin regulates endocytic recycling in a Rho-independent manner. Depletion of RTKN-1 caused recycling cargo overaccumulated in cytosol and actin filament structure severely diminished. Nevertheless, in vitro assay found RTKN-1 has no influence on actin polymerization and depolymerization. In the current study, we will examine the functional position of RTKN-1 in endocytic recycling, clarify the molecular mechanism of RTKN-1 managing actin dynamics, reveal the functional significance of RTKN-1-mediated actin dynamics in recycling transport, and examine the conservatism of recycling regulation by Rhotekin in mammals and its relationship with cancer biogenesis and progression. Taken together, our study will expand the understanding of the functional role of the actin cytoskeleton in endocytic recycling and provide clinical intervention clues for endocytic recycling disorder related diseases.