Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Centre for Mathematical Biology, Mathematical Institute, 24-29 St Giles, Oxford OX1 3LB, UK.
Dev Cell. 2014 Mar 31;28(6):659-69. doi: 10.1016/j.devcel.2014.02.013. Epub 2014 Mar 20.
Centrosomes are important cell organizers. They consist of a pair of centrioles surrounded by pericentriolar material (PCM) that expands dramatically during mitosis-a process termed centrosome maturation. How centrosomes mature remains mysterious. Here, we identify a domain in Drosophila Cnn that appears to be phosphorylated by Polo/Plk1 specifically at centrosomes during mitosis. The phosphorylation promotes the assembly of a Cnn scaffold around the centrioles that is in constant flux, with Cnn molecules recruited continuously around the centrioles as the scaffold spreads slowly outward. Mutations that block Cnn phosphorylation strongly inhibit scaffold assembly and centrosome maturation, whereas phosphomimicking mutations allow Cnn to multimerize in vitro and to spontaneously form cytoplasmic scaffolds in vivo that organize microtubules independently of centrosomes. We conclude that Polo/Plk1 initiates the phosphorylation-dependent assembly of a Cnn scaffold around centrioles that is essential for efficient centrosome maturation in flies.
中心体是重要的细胞组织者。它们由一对中心粒组成，周围环绕着中心粒周围物质（PCM），在有丝分裂过程中 PCM 会显著扩张——这一过程被称为中心体成熟。中心体如何成熟仍然是个谜。在这里，我们在果蝇 Cnn 中鉴定出一个结构域，该结构域似乎在有丝分裂期间被 Polo/Plk1 特异性地磷酸化。这种磷酸化促进了围绕中心粒的 Cnn 支架的组装，该支架处于不断变化的状态，随着支架缓慢向外扩展，Cnn 分子不断地被募集到中心粒周围。阻止 Cnn 磷酸化的突变强烈抑制支架组装和中心体成熟，而磷酸模拟突变允许 Cnn 在体外多聚化，并在体内自发形成细胞质支架，这些支架独立于中心体组织微管。我们得出结论，Polo/Plk1 启动了 Cnn 支架在中心粒周围的磷酸化依赖性组装，这对于果蝇中有效的中心体成熟是必不可少的。
