真核生物鞭毛或纤毛解聚的分子基础

纤毛或鞭毛是以细胞微管为主而形成的突出于细胞表面的结构，起着细胞运动和感应器官的作用。它感应细胞周围的环境,调控动物的发育和调节各组织器官的正常生理功能。纤毛在形成、维系、或功能上的缺陷会导致发育异常或疾病包括肾脏疾病，内脏翻转等。纤毛解聚活性是纤毛形成和维系的重要因素，同时也参与了细胞周期与细胞分化。我们的工作模型是细胞内源或外源信号诱导信号传导过程包括钙离子和蛋白质磷酸化的变化，进而调控“鞭毛内运输”（IFT）及其他效应分子，从而导致轴丝微管的解聚和轴丝附属结构的解体。我们利用模式生物衣藻作为模型研究纤毛解聚的分子机理。本项目研究的内容包括1）鞭毛解聚重要蛋白或基因的鉴定；2）细胞周期素依赖激酶的类激酶 CDKL1的磷酸化机制与分子功能；3）钙离子参与纤毛解聚的机制与IFT运输的调控。我们的研究将有助于从分子机理上增强对纤毛调控的认识，并将为纤毛相关疾病的诊断、预防和治疗提供理论基础。

Cilia and flagella (interchangeable terms) are microtubule-based cellular surface protrusions. They play essential roles in cell motility, signaling and cell division to regulate various cellular processes including sensory transduction, development, tissues and organ homeostasis. Thus, defects in the structure and/or function of cilia/flagella have been implicated in various human disorders including renal disease, respiratory disorders, development abnormality and even diabetes. The formation, length control and resorption of cilia require coordinated regulation of assembly and disassembly activities. Suppression of disassembly is required for cilia formation and maintenance, whereas activation of disassembly is essential for resorption of cilia/flagella, which is prelude to cell division, differentiation and response to stress. We are using Chlamydomonas reinhardii, a unicellular green alga, as a model organism to study the mechanisms underlying ciliary resorption. In this proposal, we propose to study the following: 1) identification of genes that are important for ciliary resorption by using comparative proteomics and mutants defective in ciliary resorption; 2) study the regulation and function of a cyclin dependent kinase like kinase whose defects inhibits ciliary resorption; 3) examine the role and regulation of calcium in regulation of ciliary disassembly and IFT transport. Since cilia are conserved cellular organelles, our research findings in Chlamydomonas will have great impact on understanding cilia-related human disorders and may provide guidance on possible diagnostics and treatment for these diseases.