Carvalho Karen Freire, Clarke Hugh J
Division of Experimental Medicine, McGill University, Montreal, QC, Canada.
Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
Commun Biol. 2025 Sep 24;8(1):1357. doi: 10.1038/s42003-025-08736-y.
At ovulation in mammals, epidermal growth factor (EGFR) signaling in the cumulus granulosa cells that enclose the egg causes them to generate an extracellular matrix and become dispersed within it. This process, termed expansion, is required for sperm to reach the egg. The extracellular signal-related kinase (ERK) pathway mediates matrix production, but the mechanism responsible for cell dispersion is poorly understood. We show that EGFR signaling activates non-muscle myosin II (NMII) in the cumulus cells and that NMII activity is required for full expansion. NMII activation does not require ERK signaling, but instead depends on the Rho-associated coiled-coil containing kinases (ROCK) and the myotonic dystrophy kinase-related CDC42-binding kinases (MRCK). Blocking ROCK or MRCK impairs the ability of the cumulus cells to migrate and reduces the number of sperm that penetrate through the cumulus layer to reach the oocyte. EGFR thus promotes cumulus layer expansion by integrating ERK-dependent production of the matrix with NMII-dependent migration of the cumulus cells within it.
在哺乳动物排卵时,包围卵子的卵丘颗粒细胞中的表皮生长因子(EGFR)信号传导会使其产生细胞外基质并分散其中。这个过程称为扩张,是精子到达卵子所必需的。细胞外信号调节激酶(ERK)途径介导基质产生,但细胞分散的机制尚不清楚。我们发现EGFR信号传导激活卵丘细胞中的非肌肉肌球蛋白II(NMII),且NMII活性是完全扩张所必需的。NMII激活不需要ERK信号传导,而是依赖于Rho相关卷曲螺旋蛋白激酶(ROCK)和强直性肌营养不良激酶相关的CDC42结合激酶(MRCK)。阻断ROCK或MRCK会损害卵丘细胞的迁移能力,并减少穿过卵丘层到达卵母细胞的精子数量。因此,EGFR通过将ERK依赖的基质产生与NMII依赖的卵丘细胞在其中的迁移整合起来,促进卵丘层扩张。