Importinβ2 介导少突胶质细胞转录因子Olig1核浆转位的分子机制研究

项目名称： Importinβ2 介导少突胶质细胞转录因子Olig1核浆转位的分子机制研究

项目编号： No.31200898

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生理学与整合生物学

项目作者： 田衍平

作者单位： 中国人民解放军第三军医大学

项目金额： 23万元

中文摘要： 少突胶质前体细胞（OPCs）分化停滞是中枢神经系统脱髓鞘疾病和髓鞘再生障碍的共同特征。前期研究表明转录因子Olig1的核浆转位在少突胶质细胞(OLs)发育分化中起重要作用，但其核浆转位的分子机制目前尚不清楚。预实验提示Olig1存在核定位信号(NLS)；蛋白S138的丝氨酸磷酸化阻止了核浆转位。因此我们推测Olig1在OLs发育不同阶段存在的核浆转位是由Olig1蛋白上的NLS介导的，NLS的磷酸化调控着Olig1蛋白的出入核反应。为此，本研究利用基因工程、免疫荧光染色等技术开展以下研究：(1)鉴定Olig1蛋白分子存在的NLS；(2)分析与Olig1相互作用的核蛋白受体；(3)NLS的磷酸化对Olig1核浆转位的调节作用及Olig1核浆转位对OLs分化成熟的影响。以期阐明Olig1分子核浆转位的分子机制及作用。本课题有望阐明OLs成熟分化的调控机制，为髓鞘再生策略提供新线索。

中文关键词： 少突胶质细胞；Olig1；核浆转位；铅离子；钙离子

英文摘要： Differentiation disorder of oligodendrocyte precursor cells (OPCs) is the common feature of demyelinated diseases of the central nervous system and myelin regeneration disorder. Nucleocytoplasmic translocation of transcription factor plays an important role in cell development and differentiation. Our previous studies showed that the transcription factor Olig1 plays an important role in oligodendrocyte development and differentiation. Nucleocytoplasmic translocation of olig1 was detected in oligodendrocyte development and differentiation, but the molecular mechanism is unclear. The experiment indicates that there are nuclear localization signals in Olig1 protein, which transfer nucleoplasm through active transport and Olig1 S138 serine phosphorylation prevents the nucleoplasm transposition reaction. In this study, the following research are carried out using genetic engineering and immunofluorescence staining technique: (1) identification of nuclear localization signals of Olig1 protein; (2) analysis of which nuclear protein receptors interacted with Olig1; (3) phosphorylation of the nuclear localization signals regulates nucleocytoplasmic translocation of Olig1, which effects development and differentiation of oligodendrocyte. This project is to prove the molecular mechanism of nucleocytoplasmic translocation o

英文关键词： Oligodendrocyte；Olig1；Nucleocytoplasmic translocation；lead ion；calcium