Laboratory of Cell and Developmental Biology, Graduate School of Bioscience, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
J Cell Sci. 2013 Nov 15;126(Pt 22):5153-65. doi: 10.1242/jcs.130476. Epub 2013 Sep 17.
Maintenance of spindle attachment to the cortex and formation of the cleavage furrow around the protruded spindle are essential for polar body extrusion (PBE) during meiotic maturation of oocytes. Although spindle movement to the cortex has been well-studied, how the spindle is maintained at the cortex during PBE is unknown. Here, we show that activation of Diaphanous-related formin mediated by mitogen-activated protein kinase (MAPK) is required for tight spindle attachment to the cortex and cleavage furrow closure during PBE in starfish (Asterina pectinifera) oocytes. A. pectinifera Diaphanous-related formin (ApDia) had a distinct localization in immature oocytes and was localized to the cleavage furrow during PBE. Inhibition of the Mos-MAPK pathway or the actin nucleating activity of formin homology 2 domain prevented cleavage furrow closure and resulted in PBE failure. In MEK/MAPK-inhibited oocytes, activation of ApDia by relief of its intramolecular inhibition restored PBE. In summary, this study elucidates a link between the Mos-MAPK pathway and Diaphanous-related formins, that is responsible for maintaining tight spindle attachment to the cortex and cleavage furrow closure during PBE.
维持纺锤体与皮层的附着以及突出纺锤体周围的分裂沟的形成对于卵母细胞减数分裂成熟过程中的极体排出(PBE)是至关重要的。尽管纺锤体向皮层的运动已经得到了很好的研究,但在 PBE 期间纺锤体如何保持在皮层上仍然未知。在这里,我们发现在海星(Asterina pectinifera)卵母细胞中,丝裂原活化蛋白激酶(MAPK)激活的 Dia 相关形成素对于 PBE 期间纺锤体与皮层的紧密附着和分裂沟的闭合是必需的。A.pectinifera Dia 相关形成素(ApDia)在未成熟卵母细胞中有明显的定位,并且在 PBE 期间定位于分裂沟。Mos-MAPK 途径或形成素同源 2 结构域的肌动蛋白成核活性的抑制阻止了分裂沟的闭合,并导致 PBE 失败。在 MEK/MAPK 抑制的卵母细胞中,通过解除其分子内抑制来激活 ApDia 恢复了 PBE。总之,本研究阐明了 Mos-MAPK 途径和 Dia 相关形成素之间的联系,该联系负责在 PBE 期间维持纺锤体与皮层的紧密附着和分裂沟的闭合。