National Research Center "Frontiers in Genetics", Department of Physiology and Metabolism, University of Geneva, Rue Michel-Servet 1, CH-1211 Geneva, Switzerland.
Dev Biol. 2013 Jan 1;373(1):26-38. doi: 10.1016/j.ydbio.2012.10.001. Epub 2012 Oct 10.
Cell polarity is crucial for many aspects of cell and developmental biology. Cytoskeleton remodeling plays an essential role in the establishment of cell polarity. In the Caenorhabditis elegans one-cell embryo, while the actomyosin cytoskeleton is required for asymmetric localization of the PAR proteins, anterior PAR proteins exert a feedback regulation on contractility. Here we identify the TAO kinase KIN-18 as a regulator of cortical contractility in the early embryo. KIN-18 negatively regulates cortical contractions in a RHO-1 dependent manner and regulates RHO-1 cortical localization. KIN-18 contributes to polarity establishment by regulating the position of the boundary between anterior and posterior PAR proteins. Although KIN-18 is involved in polarity establishment, depletion of KIN-18 restores contractions in a par-3 mutant indicating that kin-18 is epistatic to par-3. We suggest a model in which KIN-18 provides a link between the cytoskeleton remodeling and polarity machineries, uncovering a role for TAO kinases in the regulation of cell polarity.
细胞极性对于细胞和发育生物学的许多方面都至关重要。细胞骨架重塑在建立细胞极性方面起着重要作用。在秀丽隐杆线虫的单细胞胚胎中,肌动球蛋白细胞骨架对于 PAR 蛋白的不对称定位是必需的,而前 PAR 蛋白对收缩性产生反馈调节。在这里,我们鉴定了 TAO 激酶 KIN-18 是早期胚胎皮质收缩的调节因子。KIN-18 以 RHO-1 依赖的方式负调控皮质收缩,并调节 RHO-1 皮质定位。KIN-18 通过调节前 PAR 蛋白和后 PAR 蛋白之间的边界位置来促进极性的建立。尽管 KIN-18 参与了极性的建立,但在 par-3 突变体中耗尽 KIN-18 会恢复收缩,表明 kin-18 是 par-3 的上位基因。我们提出了一个模型,其中 KIN-18 提供了细胞骨架重塑和极性机制之间的联系,揭示了 TAO 激酶在细胞极性调节中的作用。