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Asterless is a scaffold for the onset of centriole assembly

机译:Asterless是中心粒组装开始的支架

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摘要

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 down regulated and are promoted by Plk4 overexpression. 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 CEP 152 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.
机译:在中心体核心和纤毛和鞭毛基部的基体中发现了质心。质心的组装和复制受Polo样激酶4(Plk4)控制:如果Plk4下调并由Plk4过表达促进,则这些过程将失败。在这里,我们显示了中心粒蛋白Asterless(Asl;人类直系同源蛋白CEP152)提供了一个保守的分子平台,其氨基末端与Plk4的神秘Polo盒相互作用,而羧基末端与中心粒蛋白Sas-4(人类的CPAP)相互作用)。果蝇Asl和人CEP 152分别是果蝇中Plk4的中心体负载和人细胞中CPAP所需的。 Asl或CEP152的耗尽导致中心体复制失败;它们的过表达导致果蝇卵中从头形成中心粒,在果蝇胚胎中复制游离中心体,并在培养的果蝇和人类细胞中扩增中心体。 Asl的Plk4结合缺陷型突变体的过表达防止了培养细胞和胚胎中的重心重复。但是,这种突变蛋白能够促进胚胎和卵母细胞中的微管组织中心(MTOC)的形成。此类MTOC具有中心粒周围物质和中心粒蛋白Sas-4,但其核心没有中心粒。通过在卵母细胞或胚胎中过表达Sas-4,可以表型形成这种无毛的MTOC。我们的发现确定了Asl作为Plk4和Sas-4的支架的独立功能,可促进自体和中心粒的复制以及中心粒周围物质的组织。

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  • 来源
    《Nature》 |2010年第7316期|P.714-718ⅴ|共6页
  • 作者单位

    Cancer Research UK Cell Cycle GeneticsGroup, University of Cambridge, Department of Genetics, Downing Street, Cambridge CB2 3EH,UK;

    rnCancer Research UK Cell Cycle GeneticsGroup, University of Cambridge, Department of Genetics, Downing Street, Cambridge CB2 3EH,UK;

    rnCancer Research UK Cell Cycle GeneticsGroup, University of Cambridge, Department of Genetics, Downing Street, Cambridge CB2 3EH,UK Stanford University School of Medicine, Stanford, California 94305, USA;

    rnCancer Research UK Cell Cycle GeneticsGroup, University of Cambridge, Department of Genetics, Downing Street, Cambridge CB2 3EH,UK;

    rnCancer Research UK Cell Cycle GeneticsGroup, University of Cambridge, Department of Genetics, Downing Street, Cambridge CB2 3EH,UK Instituto Gulbenkian de Ciencia,Oeiras P-2780-156, Portugal;

    rnDipartimento di Biologia Evolutiva, Universita di Siena, via Aldo Moro, 2-53100 Siena, Italy;

    rnCancer Research UK Cell Cycle GeneticsGroup, University of Cambridge, Department of Genetics, Downing Street, Cambridge CB2 3EH,UK Instituto Gulbenkian de Ciencia,Oeiras P-2780-156, Portugal;

    rnInstituto Gulbenkian de Ciencia,Oeiras P-2780-156, Portugal;

    Dipartimento di Biologia Evolutiva, Universita di Siena, via Aldo Moro, 2-53100 Siena, Italy;

    rnCancer Research UK Cell Cycle GeneticsGroup, University of Cambridge, Department of Genetics, Downing Street, Cambridge CB2 3EH,UK;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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