Fu Jingyan, Lipinszki Zoltan, Rangone Hélène, Min Mingwei, Mykura Charlotte, Chao-Chu Jennifer, Schneider Sandra, Dzhindzhev Nikola S, Gottardo Marco, Riparbelli Maria Giovanna, Callaini Giuliano, Glover David M
Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
Department of Life Sciences, University of Siena, Via A. Moro 4, 53100 Siena, Italy.
Nat Cell Biol. 2016 Jan;18(1):87-99. doi: 10.1038/ncb3274. Epub 2015 Nov 23.
Centrioles are required to assemble centrosomes for cell division and cilia for motility and signalling. New centrioles assemble perpendicularly to pre-existing ones in G1-S and elongate throughout S and G2. Fully elongated daughter centrioles are converted into centrosomes during mitosis to be able to duplicate and organize pericentriolar material in the next cell cycle. Here we show that centriole-to-centrosome conversion requires sequential loading of Cep135, Ana1 (Cep295) and Asterless (Cep152) onto daughter centrioles during mitotic progression in both Drosophila melanogaster and human. This generates a molecular network spanning from the inner- to outermost parts of the centriole. Ana1 forms a molecular strut within the network, and its essential role can be substituted by an engineered fragment providing an alternative linkage between Asterless and Cep135. This conserved architectural framework is essential for loading Asterless or Cep152, the partner of the master regulator of centriole duplication, Plk4. Our study thus uncovers the molecular basis for centriole-to-centrosome conversion that renders daughter centrioles competent for motherhood.
中心粒对于组装用于细胞分裂的中心体以及用于运动和信号传导的纤毛是必需的。新的中心粒在G1-S期垂直于已有的中心粒组装,并在整个S期和G2期延长。完全延长的子中心粒在有丝分裂期间转化为中心体,以便能够在下一个细胞周期中复制并组织中心粒周围物质。在这里,我们表明,在果蝇和人类的有丝分裂进程中,中心粒到中心体的转化需要在子中心粒上依次加载Cep135、Ana1(Cep295)和无星状体(Cep152)。这产生了一个从中心粒内部延伸到最外部的分子网络。Ana1在网络中形成一个分子支柱,其关键作用可以被一个工程片段替代,该片段在无星状体和Cep135之间提供了另一种连接。这种保守的结构框架对于加载无星状体或Cep152是必不可少的,Cep152是中心粒复制主调节因子Plk4的伙伴。因此,我们的研究揭示了中心粒到中心体转化的分子基础,使子中心粒能够成为母中心粒。