The Gurdon Institute, Cambridge, England CB2 1QN, UK.
J Cell Biol. 2010 Feb 8;188(3):313-23. doi: 10.1083/jcb.200910016. Epub 2010 Feb 1.
In Caenorhabditis elegans, five proteins are required for centriole duplication: SPD-2, ZYG-1, SAS-5, SAS-6, and SAS-4. Functional orthologues of all but SAS-5 have been found in other species. In Drosophila melanogaster and humans, Sak/Plk4, DSas-6/hSas-6, and DSas-4/CPAP-orthologues of ZYG-1, SAS-6, and SAS-4, respectively-are required for centriole duplication. Strikingly, all three fly proteins can induce the de novo formation of centriole-like structures when overexpressed in unfertilized eggs. Here, we find that of eight candidate duplication factors identified in cultured fly cells, only two, Ana2 and Asterless (Asl), share this ability. Asl is now known to be essential for centriole duplication in flies, but no equivalent protein has been found in worms. We show that Ana2 is the likely functional orthologue of SAS-5 and that it is also related to the vertebrate STIL/SIL protein family that has been linked to microcephaly in humans. We propose that members of the SAS-5/Ana2/STIL family of proteins are key conserved components of the centriole duplication machinery.
在秀丽隐杆线虫中，有五种蛋白质对于中心体复制是必需的：SPD-2、ZYG-1、SAS-5、SAS-6 和 SAS-4。除了 SAS-5 之外，所有这些蛋白质在其他物种中都有功能同源物。在果蝇和人类中，Sak/Plk4、DSas-6/hSas-6 和 DSas-4/CPAP-分别是 ZYG-1、SAS-6 和 SAS-4 的功能同源物，对于中心体复制是必需的。引人注目的是，当这三种果蝇蛋白在未受精的卵中过表达时，都可以诱导中心体样结构的从头形成。在这里，我们发现，在培养的果蝇细胞中鉴定出的八个候选复制因子中，只有 Ana2 和 Asterless（Asl）这两种蛋白具有这种能力。Asl 现在被认为是果蝇中心体复制所必需的，但在蠕虫中没有发现等效蛋白。我们表明，Ana2 可能是 SAS-5 的功能同源物，它也与脊椎动物 STIL/SIL 蛋白家族有关，该家族与人类的小头畸形有关。我们提出，SAS-5/Ana2/STIL 蛋白家族的成员是中心体复制机制的关键保守成分。
