University of Rennes, CNRS - UMR 6290, Institute of Genetics and Development of Rennes , Rennes, France.
J Cell Biol. 2023 Nov 6;222(11). doi: 10.1083/jcb.202211029. Epub 2023 Aug 31.
Asymmetric meiotic divisions in oocytes rely on spindle positioning in close vicinity to the cortex. In metaphase II mouse oocytes, eccentric spindle positioning triggers cortical polarization, including the build-up of an actin cap surrounded by a ring of activated myosin II. While the role of the actin cap in promoting polar body formation is established, ring myosin II activation mechanisms and functions have remained elusive. Here, we show that ring myosin II activation requires myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK), downstream of polarized Cdc42. MRCK inhibition resulted in spindle rotation defects during anaphase II, precluding polar body extrusion. Remarkably, disengagement of segregated chromatids from the anaphase spindle could rescue rotation. We further show that the MRCK/myosin II pathway is activated in the fertilization cone and is required for male pronucleus migration toward the center of the zygote. These findings provide novel insights into the mechanism of myosin II activation in oocytes and its role in orchestrating asymmetric division and pronucleus centration.
卵母细胞的不对称减数分裂依赖于纺锤体在靠近皮质的位置定位。在中期 II 期的小鼠卵母细胞中，偏心纺锤体定位引发皮质极化，包括由激活的肌球蛋白 II 环包围的肌动蛋白帽的形成。虽然肌动蛋白帽在促进极体形成中的作用已经确立，但环肌球蛋白 II 的激活机制和功能仍然难以捉摸。在这里，我们表明环肌球蛋白 II 的激活需要肌强直性营养不良激酶相关的 Cdc42 结合激酶（MRCK），这是极化的 Cdc42 的下游。MRCK 抑制导致后期 II 期纺锤体旋转缺陷，阻止极体挤出。值得注意的是，从后期纺锤体上分离出分离的染色单体可以挽救旋转。我们进一步表明，MRCK/肌球蛋白 II 途径在受精锥中被激活，并且对于雄性原核向合子中心的迁移是必需的。这些发现为卵母细胞中肌球蛋白 II 激活的机制及其在协调不对称分裂和原核中心化中的作用提供了新的见解。
