胞浆Olig1与Tubulin相互作用调控少突胶质细胞突起生长的机制研究

项目名称： 胞浆Olig1与Tubulin相互作用调控少突胶质细胞突起生长的机制研究

项目编号： No.31300906

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 牛建钦

作者单位： 中国人民解放军第三军医大学

项目金额： 25万元

中文摘要： 少突胶质细胞（OL）分化调控机制的研究对促进髓鞘再生意义重大。我们最新研究发现胞浆定位Olig1与细胞突起生长密切相关。以此为基础，本课题将进一步探讨磷酸化修饰的Olig1在调控Tubulin聚合，促进少突胶质细胞突起生长中的作用和机制。利用原代OPC培养、Olig1敲基因小鼠和脱髓鞘模型：（1）明确Olig1与Tubulin的共定位及相互结合与突起生长的关系；（2）鉴定Olig1与Tubulin的结合区域及区域内关键修饰位点；（3）验证Olig1与Tubulin的结合在髓鞘形成、再生中的作用。最终证明胞浆中的Olig1通过特异区域中磷酸化修饰，加强其与Tubulin的结合，促进微管聚合，进而促进早期分化细胞的突起生长。该课题的完成不仅有助于发现Olig1调控OL突起生长的新功能，也可阐明OL形态分化成熟的新调控机制，为促进OL发育成熟的策略研究和后续药物靶标的选择提供新的基础资料。

中文关键词： 少突胶质细胞；Olig1；Tubulin；磷酸化；髓鞘形成

英文摘要： To understand the mechanism of oligodendrocyte differentiation and maturation is significantly important for remyelination process. We recently found that cytoplasmic Olig1 associated with the cell processes outgrowth in premature (or mature) oligodendrocytes. Based on this observation, our proposed investigation will focus on the effect and mechanism by which phosphorylated Olig1 regulates Tubulin polymerization and then promotes cell processes outgrowth. Applying OPC cultures, Olig1 knockout mice as well as Cuprizone-induced demyelination mice models, we will: (1) To examine the interaction and co-localization of Olig1 with Tubulin in the process of differentiation and remyelination. (2) To map the binding domain of them and identify the critical modification affecting their interaction. (3) To validate Olig1 as a key promoter on the maturation and remyelination process via promoting tubulin polymerization. Finally we want to prove our hypothesis that phosphorylated Olig1 in cytosol enhances the interaction with Tubulin to promote polymerization and advance the processes outgrowth in early development. Our study may not only demonstrate the new function of Olig1 in manipulate the processes outgrowth of OL, but also provide a new insight into the mechanism of oligodendrocyte differentiation which benefits a nov

英文关键词： Oligodendrocyte；Olig1；Tubulin；Phosphorylation；Myelination