Center for Cell Dynamics, Department of Cell Biology, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Baltimore, MD 21205, USA.
Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Sci Adv. 2020 Apr 3;6(14):eaaz5004. doi: 10.1126/sciadv.aaz5004. eCollection 2020 Apr.
Patterned cell divisions require a precisely oriented spindle that segregates chromosomes and determines the cytokinetic plane. In this study, we investigated how the meiotic spindle orients through an obligatory rotation during meiotic division in mouse oocytes. We show that spindle rotation occurs at the completion of chromosome segregation, whereby the separated chromosome clusters each define a cortical actomyosin domain that produces cytoplasmic streaming, resulting in hydrodynamic forces on the spindle. These forces are initially balanced but become unbalanced to drive spindle rotation. This force imbalance is associated with spontaneous symmetry breaking in the distribution of the Arp2/3 complex and myosin-II on the cortex, brought about by feedback loops comprising Ran guanosine triphosphatase signaling, Arp2/3 complex activity, and myosin-II contractility. The torque produced by the unbalanced hydrodynamic forces, coupled with a pivot point at the spindle midzone cortical contract, constitutes a unique mechanical system for meiotic spindle rotation.
有丝分裂需要一个精确取向的纺锤体，它可以分离染色体并确定细胞分裂平面。在这项研究中，我们研究了在小鼠卵母细胞减数分裂过程中，减数分裂纺锤体如何通过强制性旋转来定向。我们表明，纺锤体旋转发生在染色体分离完成时，此时分离的染色体簇各自定义了一个皮质肌动球蛋白域，产生细胞质流动，从而对纺锤体产生流体动力。这些力最初是平衡的，但会失去平衡，从而驱动纺锤体旋转。这种力的不平衡与皮层上 Arp2/3 复合物和肌球蛋白-II 分布的自发对称破缺有关，这种对称破缺是由 Ran GTP 酶信号、Arp2/3 复合物活性和肌球蛋白-II 收缩性组成的反馈环引起的。不平衡的流体动力产生的扭矩，加上纺锤体中部皮质收缩的支点，构成了一个独特的机械系统，用于减数分裂纺锤体旋转。
