Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
Mol Biol Cell. 2012 Oct;23(20):4020-31. doi: 10.1091/mbc.E12-04-0268. Epub 2012 Aug 23.
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.
RhoA 是一种 GTP 酶，它在多种生物过程中充当细胞收缩的核心调节剂。在此过程中，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 的激活发生在适当的时间和地点。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，而 CYK-4 是中心纺锤体复合物的一个组成部分。相比之下，在早期秀丽隐杆线虫胚胎中，并非所有依赖于 ECT-2 的功能都需要 CYK-4。在这项研究中，我们鉴定了一种新的蛋白 NOP-1，它与 CYK-4 平行发挥作用，促进 RhoA 的激活。我们利用 nop-1 和 cyk-4 的突变来剖析胞质分裂和细胞极化。NOP-1 对胞质分裂有重要贡献，尽管这种贡献在很大程度上是冗余的。相比之下，NOP-1 对于极化建立阶段的 RhoA 激活占主导地位是必需的。
