USP21调控纤毛发生的分子机制和生理功能

纤毛是一种伸出细胞表面用于感知外界信号的细胞器，在组织器官发育过程中扮演着重要角色，纤毛异常将导致纤毛疾病的产生。虽然目前已发现泛素系统能参与纤毛发生的调控，但具体的调控机制和参与蛋白仍有待进一步的探究和鉴定。在本项目中，我们计划从前期工作发现的具有纤毛调控功能的去泛素化酶USP21入手，寻找被USP21去泛素化调控的纤毛调控分子，深入探究以USP21为起点的去泛素化调控在纤毛发生过程中的功能和分子机制，并初步揭示相关蛋白在生理、病理中的作用。我们前期的工作已初步完成以USP21为诱饵的质谱鉴定工作，并获得了USP21基因敲除小鼠。我们后续将继续深入分析质谱数据，进而探索一条以USP21的去泛素化过程为起始、以纤毛调控的分子机制为核心、以组织器官发育功能为归宿的信号通路。考虑到纤毛的生理病理重要性，本项目将进一步深化和细化目前对纤毛发生机制的研究，为相关疾病的治疗和药物的研发提供理论基础。

Primary cilium is a microtubule-based structure that extends from the surface of the cell. It plays an important role in sensing signals and regulating physiological functions of the cell, and dysregulation in this organelle leads to human diseases. Although recent studies show an emerging role of ubiquitin-proteasome system in cilia formation, the detailed mechanisms and potential players underlying ciliogenesis regulation still merit further exploration. In this project, we will use USP21 as a bait, and screen for its potential deubiquitination targets involved in cilia-related functions. We will also investigate the functions of the involved proteins in human diseases, and the molecular pathways that contribute to cilia formation and ciliopathy. Our preliminary data have obtained the USP21-interacting proteins by mass spectrum analysis, and the USP21 knockout mice have also been successfully generated. Therefore, further efforts will be applied to exploring the protein network deubiquitinated by USP21, the molecular pathways underlying ciliogenesis, and the physiological functions of the involved proteins. We hope to reveal the molecular mechanism of the cilia formation and regulation, and provide theoretical foundations for future clinical applications in ciliogenesis defects.