Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland.
Dev Cell. 2011 Apr 19;20(4):550-62. doi: 10.1016/j.devcel.2011.02.005.
Centrosome duplication occurs once per cell cycle and ensures that the two resulting centrosomes assemble a bipolar mitotic spindle. Centriole formation is fundamental for centrosome duplication. In Caenorhabditis elegans, the evolutionarily conserved proteins SPD-2, ZYG-1, SAS-6, SAS-5, and SAS-4 are essential for centriole formation, but how they function is not fully understood. Here, we demonstrate that Protein Phosphatase 2A (PP2A) is also critical for centriole formation in C. elegans embryos. We find that PP2A subunits genetically and physically interact with the SAS-5/SAS-6 complex. Furthermore, we show that PP2A-mediated dephosphorylation promotes centriolar targeting of SAS-5 and ensures SAS-6 delivery to the site of centriole assembly. We find that PP2A is similarly needed for the presence of HsSAS-6 at centrioles and for centriole formation in human cells. These findings lead us to propose that PP2A-mediated loading of SAS-6 proteins is critical at the onset of centriole formation.
中心体复制发生在每个细胞周期一次，以确保两个中心体组装成一个双极有丝分裂纺锤体。中心粒的形成对于中心体的复制是必不可少的。在秀丽隐杆线虫中，进化上保守的蛋白质 SPD-2、ZYG-1、SAS-6、SAS-5 和 SAS-4 对于中心粒的形成是必不可少的，但它们的功能尚不完全清楚。在这里，我们证明蛋白磷酸酶 2A（PP2A）对于线虫胚胎中的中心粒形成也是至关重要的。我们发现 PP2A 亚基在遗传和物理上与 SAS-5/SAS-6 复合物相互作用。此外，我们还表明，PP2A 介导的去磷酸化促进了 SAS-5 向中心粒的靶向，并确保了 SAS-6 递送到中心体组装的部位。我们发现 PP2A 对于人源细胞中 HsSAS-6 存在于中心粒上和中心粒的形成也是必需的。这些发现使我们提出，PP2A 介导的 SAS-6 蛋白的加载对于中心粒的形成至关重要。
