Biology, Indian Institute of Science Education and Research, Pune, India.
Elife. 2021 Apr 9;10:e63535. doi: 10.7554/eLife.63535.
Actomyosin contractility is regulated by Rho-GTP in cell migration, cytokinesis and morphogenesis in embryo development. Whereas Rho activation by Rho-GTP exchange factor (GEF), RhoGEF2, is well known in actomyosin contractility during cytokinesis at the base of invaginating membranes in cellularization, Rho inhibition by RhoGTPase-activating proteins (GAPs) remains to be studied. We have found that the RhoGAP, GRAF, inhibits actomyosin contractility during cellularization. GRAF is enriched at the cleavage furrow tip during actomyosin assembly and initiation of ring constriction. depletion shows increased Rho-GTP, increased Myosin II and ring hyper constriction dependent upon the loss of the RhoGTPase domain. GRAF and RhoGEF2 are present in a balance for appropriate activation of actomyosin ring constriction. RhoGEF2 depletion and abrogation of Myosin II activation in Rho kinase mutants suppress the hyper constriction defect. Therefore, GRAF recruitment restricts Rho-GTP levels in a spatiotemporal manner for inhibiting actomyosin contractility during cellularization.
肌动球蛋白收缩性通过 Rho-GTP 在细胞迁移、胞质分裂和胚胎发育形态发生中调节。尽管 Rho-GTP 交换因子（GEF）RhoGEF2 的 Rho 激活在胞质分裂期间在细胞化中内陷膜的基底处的肌动球蛋白收缩性中是众所周知的，但 RhoGTP 酶激活蛋白（GAPs）的 Rho 抑制仍有待研究。我们发现 RhoGAP、GRAF 在细胞化过程中抑制肌动球蛋白收缩性。在肌动球蛋白组装和环收缩开始时，GRAF 在分裂沟尖端富集。耗尽显示 Rho-GTP 增加、肌球蛋白 II 增加和环过度收缩，这取决于 RhoGTP 酶结构域的缺失。GRAF 和 RhoGEF2 处于平衡状态，以适当激活肌动球蛋白环收缩。RhoGEF2 耗竭和肌球蛋白 II 激活在 Rho 激酶突变体中的消除抑制了过度收缩缺陷。因此，GRAF 募集以时空方式限制 Rho-GTP 水平，以抑制细胞化过程中的肌动球蛋白收缩性。
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