Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Dev Cell. 2011 Apr 19;20(4):563-71. doi: 10.1016/j.devcel.2011.03.007.
Centrioles play a crucial role in mitotic spindle assembly and duplicate precisely once per cell cycle. In worms, flies, and humans, centriole assembly is dependent upon a key regulatory kinase (ZYG-1/Sak/Plk4) and its downstream effectors SAS-5 and SAS-6. Here we report a role for protein phosphatase 2A (PP2A) in centriole duplication. We find that the PP2A catalytic subunit LET-92, the scaffolding subunit PAA-1, and the B55 regulatory subunit SUR-6 function together to positively regulate centriole assembly. In PP2A-SUR-6-depleted embryos, the levels of ZYG-1 and SAS-5 are reduced and the ZYG-1- and SAS-5-dependent recruitment of SAS-6 to the nascent centriole fails. We show that PP2A physically associates with SAS-5 in vivo and that inhibiting proteolysis can rescue SAS-5 levels and the centriole duplication defect of PP2A-depleted embryos. Together, our findings indicate that PP2A-SUR-6 promotes centriole assembly by protecting ZYG-1 and SAS-5 from degradation.
中心体在有丝分裂纺锤体组装中起着至关重要的作用，并且在细胞周期中精确复制一次。在蠕虫、苍蝇和人类中，中心体的组装依赖于关键调节激酶（ZYG-1/Sak/Plk4）及其下游效应物 SAS-5 和 SAS-6。在这里，我们报告了蛋白磷酸酶 2A（PP2A）在中心体复制中的作用。我们发现 PP2A 的催化亚基 LET-92、支架亚基 PAA-1 和 B55 调节亚基 SUR-6 共同正向调节中心体的组装。在 PP2A-SUR-6 耗尽的胚胎中，ZYG-1 和 SAS-5 的水平降低，并且 ZYG-1 和 SAS-5 依赖的 SAS-6 向新生中心体的募集失败。我们表明 PP2A 在体内与 SAS-5 物理结合，并且抑制蛋白水解可以挽救 PP2A 耗尽胚胎中 SAS-5 水平和中心体复制缺陷。总之，我们的发现表明 PP2A-SUR-6 通过保护 ZYG-1 和 SAS-5 免受降解来促进中心体的组装。
