Sequential actin-based pushing forces drive meiosis I chromosome migration and symmetry breaking in oocytes.

Sequential actin-based pushing forces drive meiosis I chromosome migration and symmetry breaking in oocytes.
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DOI:
10.1083/jcb.201211068
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发表时间:
2013-03-04
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Li R
Li R
中科院分区:
其他
文献类型:
--
作者:
Yi K;Rubinstein B;Unruh JR;Guo F;Slaughter BD;Li R

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减数分裂I染色体迁移是双相的,早期,缓慢的阶段需要Fmn 2和后期,快速和高度定向的阶段需要Arp 2/3复合物。卵母细胞成熟过程中的极体挤出严重依赖于减数分裂纺锤体的不对称定位,这是通过减数分裂I(MI)纺锤体/染色体从卵母细胞内部迁移到皮质下位置而建立的。在这项研究中,我们表明,MI染色体迁移是双相的,并通过连续的肌动蛋白为基础的推动力,由两个肌动蛋白成核剂,Fmn 2,一个cardiac家族蛋白,和Arp 2/3复合物调节。FMN 2被募集到MI纺锤体周围的内质网结构,在那里它使肌动蛋白丝成核,以启动纺锤体远离细胞中心的最初缓慢且定向不良的运动。一个快速和高度定向的第二个迁移阶段是由肌动蛋白介导的细胞质流驱动的,并发生在染色体到达足够接近皮质激活Arp 2/3复合物。我们建议,在小鼠卵母细胞中的决定性对称性破缺的结果从Fmn 2介导的扰动的纺锤体的位置和染色体信号诱导的Arp 2/3激活和Arp 2/3协调的细胞质流,运输染色体之间的正反馈回路。
Meiosis I chromosome migration is biphasic, with an early, slow phase requiring Fmn2 and a later, fast and highly directed phase requiring the Arp2/3 complex. Polar body extrusion during oocyte maturation is critically dependent on asymmetric positioning of the meiotic spindle, which is established through migration of the meiosis I (MI) spindle/chromosomes from the oocyte interior to a subcortical location. In this study, we show that MI chromosome migration is biphasic and driven by consecutive actin-based pushing forces regulated by two actin nucleators, Fmn2, a formin family protein, and the Arp2/3 complex. Fmn2 was recruited to endoplasmic reticulum structures surrounding the MI spindle, where it nucleated actin filaments to initiate an initially slow and poorly directed motion of the spindle away from the cell center. A fast and highly directed second migration phase was driven by actin-mediated cytoplasmic streaming and occurred as the chromosomes reach a sufficient proximity to the cortex to activate the Arp2/3 complex. We propose that decisive symmetry breaking in mouse oocytes results from Fmn2-mediated perturbation of spindle position and the positive feedback loop between chromosome signal-induced Arp2/3 activation and Arp2/3-orchestrated cytoplasmic streaming that transports the chromosomes.
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