Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation.
Aurora A and cortical flows promote polarization and cytokinesis by inducing asymmetric ECT-2 accumulation.
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DOI：
10.7554/elife.83992
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发表时间：
2022-12-19
期刊：
影响因子：
7.7
通讯作者：
Glotzer, Michael
中科院分区：
文献类型：
--
作者：
Longhini, Katrina M.;Glotzer, Michael
在秀丽线虫早期胚胎中，细胞极化和胞质分裂是相互联系但又截然不同的过程。在这里，我们试图了解乳沟定位的一个鲜为人知的方面。早期线虫胚胎缺乏细胞动力学调节中心纺锤体形成皱纹，这是由于一种抑制活性依赖于星座相对于极皮层的位置。在这里，我们显示极地松弛与皮质ECT-2的耗竭有关，ECT-2是一种Rhogef，特别是在后皮质。不对称的ECT-2聚集需要完整的中心体、Aurora A(AIR-1)和肌球蛋白依赖的皮质血流。在一个具有定位能力的ECT-2片段中，我们在ECT-2的PH结构域中确定了三个假定的磷酸受体位点，使ECT-2对AIR-1的抑制做出反应。在极化和胞质分裂过程中，我们的结果表明中心体AIR-1通过ECT-2磷酸化破坏对称性；这种对ECT-2的局部抑制被肌球蛋白驱动的流动放大，从而产生局部ECT-2不对称。这些机制共同作用，诱导皮质肌球蛋白的极化组装，促进胚胎极化和胞质分裂。
In the early Caenorhabditis elegans embryo, cell polarization and cytokinesis are interrelated yet distinct processes. Here, we sought to understand a poorly understood aspect of cleavage furrow positioning. Early C. elegans embryos deficient in the cytokinetic regulator centralspindlin form furrows, due to an inhibitory activity that depends on aster positioning relative to the polar cortices. Here, we show polar relaxation is associated with depletion of cortical ECT-2, a RhoGEF, specifically at the posterior cortex. Asymmetric ECT-2 accumulation requires intact centrosomes, Aurora A (AIR-1), and myosin-dependent cortical flows. Within a localization competent ECT-2 fragment, we identified three putative phospho-acceptor sites in the PH domain of ECT-2 that render ECT-2 responsive to inhibition by AIR-1. During both polarization and cytokinesis, our results suggest that centrosomal AIR-1 breaks symmetry via ECT-2 phosphorylation; this local inhibition of ECT-2 is amplified by myosin-driven flows that generate regional ECT-2 asymmetry. Together, these mechanisms cooperate to induce polarized assembly of cortical myosin, contributing to both embryo polarization and cytokinesis.