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Dynamic organelle distribution initiates actin-based spindle migration in mouse oocytes.
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-14 , DOI: 10.1038/s41467-019-14068-3
Xing Duan 1, 2 , Yizeng Li 3, 4 , Kexi Yi 5 , Fengli Guo 5 , HaiYang Wang 1, 2 , Pei-Hsun Wu 2 , Jing Yang 4 , Devin B Mair 1, 2, 6 , Edwin Angelo Morales 1 , Petr Kalab 2 , Denis Wirtz 2 , Sean X Sun 4 , Rong Li 1, 2, 7
Affiliation  

Migration of meiosis-I (MI) spindle from the cell center to a sub-cortical location is a critical step for mouse oocytes to undergo asymmetric meiotic cell division. In this study, we investigate the mechanism by which formin-2 (FMN2) orchestrates the initial movement of MI spindle. By defining protein domains responsible for targeting FMN2, we show that spindle-periphery localized FMN2 is required for spindle migration. The spindle-peripheral FMN2 nucleates short actin bundles from vesicles derived likely from the endoplasmic reticulum (ER) and concentrated in a layer outside the spindle. This layer is in turn surrounded by mitochondria. A model based on polymerizing actin filaments pushing against mitochondria, thus generating a counter force on the spindle, demonstrated an inherent ability of this system to break symmetry and evolve directional spindle motion. The model is further supported through experiments involving spatially biasing actin nucleation via optogenetics and disruption of mitochondrial distribution and dynamics.

中文翻译:

动态细胞器分布在小鼠卵母细胞中启动基于肌动蛋白的纺锤体迁移。

减数分裂-I(MI)纺锤体从细胞中心迁移到皮质下位置是小鼠卵母细胞经历不对称减数分裂细胞分裂的关键步骤。在这项研究中,我们研究了formin-2(FMN2)协调MI主轴的初始运动的机制。通过定义负责靶向FMN2的蛋白质结构域,我们表明纺锤体迁移需要纺锤外围局部的FMN2。纺锤体周围的FMN2使可能来自内质网(ER)的囊泡中的短肌动蛋白束成核,并集中在纺锤体外部的一层中。该层又被线粒体包围。基于聚合肌动蛋白丝推动线粒体,从而在纺锤上产生反作用力的模型,证明了该系统具有打破对称性并发展主轴定向运动的固有能力。通过涉及通过光遗传学对空间肌动蛋白成核,线粒体分布和动力学破坏的实验,进一步支持了该模型。
更新日期:2020-01-14
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