蛋白激酶LIMK1活性在小鼠卵母细胞染色体分离过程中的作用和分子机制

项目名称： 蛋白激酶LIMK1活性在小鼠卵母细胞染色体分离过程中的作用和分子机制

项目编号： No.31271253

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 马伟

作者单位： 首都医科大学

项目金额： 80万元

中文摘要： 非整倍体胚胎常由卵母细胞染色体分离错误所致，引起流产或出生缺陷。纺锤体牵引染色体分离，而动粒上纺锤体组装检验点(Spindle Assembly Checkpoint, SAC)则调控细胞分裂后期启动和染色体适时分离。我们在前期工作中发现蛋白激酶LIMK1(Lim kinase 1)分布于小鼠卵母细胞减数分裂纺锤体上，磷酸化LIMK1同时存在于微管组织中心(microtubule organizing centers，MTOCs)和动粒上，并与gamma-tubulin 之间存在生理性相互作用，提示LIMK1活性参与纺锤体形成并与SAC功能相关。本项目继续探索LIMK1在MTOC形成和维持以及SAC功能建立过程中的作用；构建卵母细胞limk1条件性敲除小鼠模型，在体性地研究LIMK1的作用。研究结果将有助于揭示卵母细胞内确保染色体精确分离的分子机制，对于认识非整倍体胚胎形成具有重要意义。

中文关键词： LIMK1；卵母细胞；染色体分离；作用；分子机制

英文摘要： Aneuploid embryos are mainly caused by oocyte chromosome segregation errors, leading to miscarriage and birth defects. The spindle functions to drive chromosome division, while spindle assembly checkpoints (SAC) on kinetochore control the onset of anaphase and timely separation of chromosome. In our previous work, the protein kinase Lim kinase 1(LIMK1) was found specially localized on spindle while phosphorylated LIMK1 is present in the microtubule organizing centers (MTOCs) and chromosome kinetochores, a physiological interaction was also observed between phosphorylated LIMK1 and gamma-tubulin in mouse oocytes during meiosis, implying LIMK1 activity is involved in spindle formation and SAC function. In this project, we will continue to explore the role of LIMK1 activity in the formation and maintenance of MTOC and the establishment of SAC function on kinetochore; establish limk1 oocytes conditional knockout mouse model, studying the role of LIMK1 in oocytes in vivo. The project findings will help to throw light on the molecular mechanism ensuring accurate chromosome segregation in oocyte, with high significance for understanding the formation of human aneuploid embryos.

英文关键词： LIMK1；oocytes；chromosome separation；role；molecular mechanism