RhoA activation during polarization and cytokinesis of the early Caenorhabditis elegans embryo is differentially dependent on NOP-1 and CYK-4.
RhoA activation during polarization and cytokinesis of the early Caenorhabditis elegans embryo is differentially dependent on NOP-1 and CYK-4.
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DOI：
10.1091/mbc.e12-04-0268
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发表时间：
2012-10
影响因子：
3.3
通讯作者：
Glotzer M
中科院分区：
文献类型：
--
作者：
Tse YC;Werner M;Longhini KM;Labbe JC;Goldstein B;Glotzer M
RhoA和Rho鸟嘌呤核苷酸交换因子ECT-2参与极化和胞质分裂。在胞质分裂过程中，ECT-2与Rho GTP酶激活蛋白Cyk-4相互作用促进RhoA的激活。一种新的蛋白质NOP-1与Cyk-4平行作用，在极化和胞质分裂过程中促进RhoA的激活。GTP酶RhoA在多种生物过程中是细胞收缩的中央调节因子。在这些事件中，RhoA被鸟嘌呤核苷酸交换因子(GEF)激活。这些分子受到高度调控，以确保RhoA激活在适当的时间和地点发生。在胞质分裂过程中，RhoA被Rhogef ECT-2激活。在人类细胞中，ECT-2的活性需要与Cyk-4结合，Cyk-4是中央纺锤体复合体的一个组成部分。相比之下，在秀丽隐杆线虫早期胚胎中，并不是所有依赖ECT-2的功能都需要Cyk-4。在这项研究中，我们发现了一种新的蛋白，NOP-1，它与Cyk-4平行发挥作用，促进RhoA的激活。我们使用NOP-1和Cyk-4的突变来分析胞质分裂和细胞极化。NOP-1对胞质分裂有重要的贡献，尽管在很大程度上是多余的。相反，在极化建立阶段，NOP-1是RhoA激活占优势所必需的。
RhoA and the Rho guanine nucleotide exchange factor ECT-2 are involved in both polarization and cytokinesis. During cytokinesis, interactions of ECT-2 with the Rho GTPase-activating protein CYK-4 promote RhoA activation. A novel protein, NOP-1, acts in parallel with CYK-4 to promote RhoA activation during polarization and cytokinesis. The GTPase RhoA is a central regulator of cellular contractility in a wide variety of biological processes. During these events, RhoA is activated by guanine nucleotide exchange factors (GEFs). These molecules are highly regulated to ensure that RhoA activation occurs at the proper time and place. During cytokinesis, RhoA is activated by the RhoGEF ECT-2. In human cells, ECT-2 activity requires its association with CYK-4, which is a component of the centralspindlin complex. In contrast, in early Caenorhabditis elegans embryos, not all ECT-2–dependent functions require CYK-4. In this study, we identify a novel protein, NOP-1, that functions in parallel with CYK-4 to promote RhoA activation. We use mutations in nop-1 and cyk-4 to dissect cytokinesis and cell polarization. NOP-1 makes a significant, albeit largely redundant, contribution to cytokinesis. In contrast, NOP-1 is required for the preponderance of RhoA activation during the establishment phase of polarization.