Asterless is a scaffold for the onset of centriole assembly
Asterless is a scaffold for the onset of centriole assembly
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DOI：
10.1038/nature09445
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发表时间：
2010-10-07
期刊：
影响因子：
64.8
通讯作者：
Glover, David M.
中科院分区：
文献类型：
--
作者：
Dzhindzhev, Nikola S.;Yu, Quan D.;Glover, David M.
中心粒存在于中心体核心，作为基体，位于纤毛和鞭毛的基部。中心粒组装和复制由Polo样激酶4（Plk 4）控制：如果Plk 4下调，这些过程失败，并由Plk 4过表达促进（1-7）。在这里，我们表明，中心粒蛋白Asterless（Asl;人的直系同源物CEP 152）提供了一个保守的分子平台，其氨基末端与Plk 4的隐蔽波罗盒相互作用，而羧基末端与中心粒蛋白Sas-4（CPAP在人类）相互作用。果蝇Asl和人CEP 152分别是果蝇中Plk 4和人细胞中CPAP的中心体装载所需的。Asl或CEP 152的缺失导致中心体复制失败;它们的过度表达导致果蝇卵中的从头中心粒形成、果蝇胚胎中的游离中心体复制以及培养的果蝇和人类细胞中的中心体扩增。过表达的Plk 4结合缺陷突变体的Asl防止中心粒复制培养的细胞和胚胎。然而，这种突变蛋白能够促进胚胎和卵母细胞中微管组织中心（MTOC）的形成。这些MTOC具有中心粒周围物质和中心粒蛋白Sas-4，但在其核心处没有中心粒。卵母细胞或胚胎中Sas-4的过表达可以模拟这种无中心MTOCs的形成。我们的研究结果确定了独立的功能Asl作为支架Plk 4和Sas-4，促进自组装和复制的中心粒和组织的中心粒周围的材料。
Centrioles are found in the centrosome core and, as basal bodies, at the base of cilia and flagella. Centriole assembly and duplication is controlled by Polo-like-kinase 4 (Plk4): these processes fail if Plk4 is downregulated and are promoted by Plk4 overexpression(1-7). Here we show that the centriolar protein Asterless (Asl; human orthologue CEP152) provides a conserved molecular platform, the amino terminus of which interacts with the cryptic Polo box of Plk4 whereas the carboxy terminus interacts with the centriolar protein Sas-4 (CPAP in humans). Drosophila Asl and human CEP152 are required for the centrosomal loading of Plk4 in Drosophila and CPAP in human cells, respectively. Depletion of Asl or CEP152 caused failure of centrosome duplication; their overexpression led to de novo centriole formation in Drosophila eggs, duplication of free centrosomes in Drosophila embryos, and centrosome amplification in cultured Drosophila and human cells. Overexpression of a Plk4-binding-deficient mutant of Asl prevented centriole duplication in cultured cells and embryos. However, this mutant protein was able to promote microtubule organizing centre (MTOC) formation in both embryos and oocytes. Such MTOCs had pericentriolar material and the centriolar protein Sas-4, but no centrioles at their core. Formation of such acentriolar MTOCs could be phenocopied by overexpression of Sas-4 in oocytes or embryos. Our findings identify independent functions for Asl as a scaffold for Plk4 and Sas-4 that facilitates self-assembly and duplication of the centriole and organization of pericentriolar material.