Peel Nina, Stevens Naomi R, Basto Renata, Raff Jordan W
The Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, United Kingdom.
Curr Biol. 2007 May 15;17(10):834-43. doi: 10.1016/j.cub.2007.04.036. Epub 2007 May 3.
Centrosomes have important roles in many aspects of cell organization, and aberrations in their number and function are associated with various diseases, including cancer. Centrosomes consist of a pair of centrioles surrounded by a pericentriolar matrix (PCM), and their replication is tightly regulated. Here, we investigate the effects of overexpressing the three proteins known to be required for centriole replication in Drosophila-DSas-6, DSas-4, and Sak.
By directly observing centriole replication in living Drosophila embryos, we show that the overexpression of GFP-DSas-6 can drive extra rounds of centriole replication within a single cell cycle. Extra centriole-like structures also accumulate in brain cells that overexpress either GFP-DSas-6 or GFP-Sak, but not DSas-4-GFP. No extra centrioles accumulate in spermatocytes that overexpress any of these three proteins. Most remarkably, the overexpression of any one of these three proteins results in the rapid de novo formation of many hundreds of centriole-like structures in unfertilized eggs, which normally do not contain centrioles.
Our data suggest that the levels of centriolar DSas-6 determine the number of daughter centrioles formed during centriole replication. Overexpression of either DSas-6 or Sak can induce the formation of extra centrioles in some tissues but not others, suggesting that centriole replication is regulated differently in different tissues. The finding that the overexpression of DSas-4, DSas-6, or Sak can rapidly induce the de novo formation of centriole-like structures in Drosophila eggs suggests that this process results from the stabilization of centriole-precursors that are normally present in the egg.
中心体在细胞组织的许多方面发挥着重要作用，其数量和功能的异常与包括癌症在内的多种疾病相关。中心体由一对被中心粒周围物质（PCM）包围的中心粒组成，其复制受到严格调控。在此，我们研究了在果蝇中过表达已知为中心粒复制所需的三种蛋白质——DSas-6、DSas-4和Sak的影响。
通过直接观察活的果蝇胚胎中的中心粒复制，我们发现GFP-DSas-6的过表达可在单个细胞周期内驱动额外轮次的中心粒复制。额外的中心粒样结构也在过表达GFP-DSas-6或GFP-Sak而非DSas-4-GFP的脑细胞中积累。过表达这三种蛋白质中的任何一种的精母细胞中都不会积累额外的中心粒。最显著的是，这三种蛋白质中任何一种的过表达都会导致未受精卵中迅速从头形成数百个中心粒样结构，而未受精卵通常不含中心粒。
我们的数据表明，中心粒DSas-6的水平决定了中心粒复制过程中形成的子中心粒数量。DSas-6或Sak的过表达可在某些组织而非其他组织中诱导额外中心粒的形成，这表明不同组织中中心粒复制受到不同的调控。DSas-4、DSas-6或Sak的过表达可在果蝇卵中迅速诱导中心粒样结构的从头形成，这一发现表明该过程源于卵中正常存在的中心粒前体的稳定化。
