中文摘要
迁移体(Migrasome)是细胞迁移过程中,在细胞尾端收缩丝上产生的新细胞器,目前的研究表明迁移体可以用于释放胞质成分,传递信息,具有重要的生理意义。因此迁移体发生机制的研究尤为重要。迁移体是在收缩丝的末端或者交叉点开始生长的囊泡,形状规则,囊泡越涨越大,最终破裂。迁移体的发生不同于传统囊泡发生机制或者细胞骨架介导的膜动态变化。依据迁移体与细胞胞体蛋白含量的定量质谱分析,我们发现离子通道富集在迁移体膜上。同时,大规模的药物筛选表明离子通道抑制剂可以有效抑制迁移体的产生。本项目将依据定量质谱和药物筛选结果,应用RNAi筛选参与迁移体产生的离子通道,并且通过生物化学,生理学,细胞生物学和体外重构的研究方法,研究离子通道参与的迁移体产生的分子机制。
英文摘要
Migrasome is generated during cell migration, when they leave long tubular strands, called retraction fibers, behind them. Migrasome first grows on the tips and intersections of retraction fibers and are finally released into the extracellular space or directly taken up by surrounding cells for intracellular contents release and signalling transduction. Thus, the mechanism of migrasome generation attracts a lot of attention. The progress of migrasome growing is different with the conventional organelle budding or cytoskeleton mediated membrane dynamics. The quantitative mass spectrum method comparing the compostion of proteins in Migrasome and in cell body indicated that ion channels were enriched in Migrasome. Moreover, ion channel inhibitors show inhibition effect on migrasome formation based on a drug screening. In this project, we will verify which ion channels participate in Migrasome generation and study the molecular mechanism using cell biology, biochemistry, physiology and in vitro reconstitution method.
