细胞核蛋白CrXAP5依赖的纤毛基因转录表达分子机制研究

纤毛/鞭毛是一类突出于细胞表面具有极性结构的细胞器，在多种组织器官细胞中发挥着重要的生物学功能。在细胞周期和发育过程中，纤毛会发生周期性的组装和解聚，纤毛组装过程中各组分有着精确的表达调控机制，而纤毛结构和功能缺陷会导致相关纤毛疾病。在前期研究中，我们发现衣藻细胞核蛋白CrXAP5调控纤毛组装过程，纤毛再生过程中，CrXAP5迅速发生磷酸化，而随着纤毛生长，CrXAP5又逐渐发生去磷酸化。进一步研究发现，CrXAP5参与了纤毛基因转录表达调控过程。本项目拟研究在纤毛组装过程中CrXAP5调控纤毛靶基因转录表达的作用机理和CrXAP5蛋白质磷酸化修饰的机制，揭示基因转录表达调控在纤毛组装过程中的作用，探明磷酸化修饰在调控纤毛基因转录表达中的功能，进一步完善基因转录水平表达调控纤毛组装理论，该研究将会为预防、诊断和治疗人类纤毛疾病提供一定的理论支持。

Cilia and flagella are polarized organelles extending from the surfaces of cells, and play important roles in a wide range of biological processes and organisms. They are dynamic structures that undergo assembly and disassembly throughout the cell cycle and during development. The expression of ciliary components are precisely coordinated during cilia assembly. Defects in cilia in humans may cause various genetic disorders which are called ciliopathies. In previous research, We find that CrXAP5 is a nucleus-localized protein and modulates flagellar assembly. CrXAP5 is phosphorylated and dephosphorylated during flagellar regeneration. Further studies show that mutation in xap5 led to decrease the expression of several conserved genes involved in the assembly and function of cilia in various organisms. This project is focused on the research that CrXAP5 modulates the expression of genes encoding ciliary proteins and the phosphorylation of CrXAP5, to uncover the mechanism by which flagellar assembly is programmed at the transcriptional level, and clarify the function of phosphorylation in the expression of ciliary genes. The findings of the research will provide a theoretical support for the prevention, diagnosis and treatment of human ciliopathies.