Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
J Cell Biol. 2022 Sep 5;221(9). doi: 10.1083/jcb.202205058. Epub 2022 Jul 21.
Centrioles duplicate once per cell cycle, but it is unclear how daughter centrioles assemble at the right time and place and grow to the right size. Here, we show that in Drosophila embryos the cytoplasmic concentrations of the key centriole assembly proteins Asl, Plk4, Ana2, Sas-6, and Sas-4 are low, but remain constant throughout the assembly process-indicating that none of them are limiting for centriole assembly. The cytoplasmic diffusion rate of Ana2/STIL, however, increased significantly toward the end of S-phase as Cdk/Cyclin activity in the embryo increased. A mutant form of Ana2 that cannot be phosphorylated by Cdk/Cyclins did not exhibit this diffusion change and allowed daughter centrioles to grow for an extended period. Thus, the Cdk/Cyclin-dependent phosphorylation of Ana2 seems to reduce the efficiency of daughter centriole assembly toward the end of S-phase. This helps to ensure that daughter centrioles stop growing at the correct time, and presumably also helps to explain why centrioles cannot duplicate during mitosis.
中心体在细胞周期中复制一次，但尚不清楚子中心体如何在正确的时间和位置组装并生长到正确的大小。在这里，我们发现在果蝇胚胎中，关键的中心体组装蛋白 Asl、Plk4、Ana2、Sas-6 和 Sas-4 的细胞质浓度较低，但在整个组装过程中保持不变-表明它们都不是中心体组装的限制因素。然而，随着胚胎中 Cdk/Cyclin 活性的增加，Ana2/STIL 的细胞质扩散速率在 S 期结束时显著增加。一种不能被 Cdk/Cyclins 磷酸化的 Ana2 突变体形式没有表现出这种扩散变化，从而允许子中心体延长生长时间。因此，Cdk/Cyclin 依赖性磷酸化 Ana2 似乎会降低 S 期结束时子中心体组装的效率。这有助于确保子中心体在正确的时间停止生长，并且大概也有助于解释为什么中心体不能在有丝分裂期间复制。
