Article

Asterless is a scaffold for the onset of centriole assembly

Cancer Research UK Cell Cycle Genetics Group, University of Cambridge, Department of Genetics, Downing Street, Cambridge CB2 3EH, UK.
Nature (Impact Factor: 41.46). 10/2010; 467(7316):714-8. DOI: 10.1038/nature09445
Source: PubMed

ABSTRACT

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. 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.

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    • "Centriole assembly is initiated by the recruitment of Polo-like kinase 4 (Plk4) to the site of centriole assembly (Dzhindzhev et al. 2010;Cizmecioglu et al. 2010;Hatch et al. 2010;Slevin et al. 2012;Sonnen et al. 2013;Kim et al. 2013;Shimanovskaya et al. 2014). In vertebrates, this step is executed through a direct physical interaction between Plk4 and its centriole receptors SPD-2 and Cep152. "
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    ABSTRACT: Centrioles play critical roles in the organization of microtubule-based structures from the mitotic spindle to cilia, and flagella. In order to properly execute their various functions, centrioles are subjected to stringent copy number control. Central to this control mechanism is a precise duplication event that takes place during S phase of the cell cycle and involves the assembly of a single daughter centriole in association with each mother centriole. Recent studies have revealed that post-translational control of the master regulator Plk4/ZYG-1 kinase and its downstream effector SAS-6 is key to ensuring production of a single daughter centriole. In contrast, relatively little is known about how centriole duplication is regulated at a transcriptional level. Here we show that the transcription factor complex EFL-1-DPL-1 both positively and negatively controls centriole duplication in the Caenorhabditis elegans embryo. Specifically, we find that down regulation of EFL-1-DPL-1 can restore centriole duplication in a zyg-1 hypomorphic mutant and that suppression of the zyg-1 mutant phenotype is accompanied by an increase in SAS-6 protein levels. Further, we find evidence that EFL-1-DPL-1 promotes the transcription of zyg-1 and other centriole duplication genes. Our results provide evidence that in a single tissue type, EFL-1-DPL-1 sets the balance between positive and negative regulators of centriole assembly and thus may be part of a homeostatic mechanism that governs centriole assembly.
    Preview · Article · Jan 2016 · G3-Genes Genomes Genetics
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    • "Similar local positive feedback circuits may operate in the spatial inheritance of other cellular structures. Our and others work suggest that PLK4 is translated and recruited to the centrosome where it accumulates (Cizmecioglu et al., 2010;Dzhindzhev et al., 2010;Fode et al., 1996;Hatch et al., 2010;Sillibourne et al., 2010;Sonnen et al., 2012) until it reaches a threshold that quickly leads to full activation of the kinase , which is essential to trigger centriole biogenesis. Active PLK4 will then target itself for degradation (Cunha-Ferreira et al., 2013;Holland et al., 2010;Klebba et al., 2013). "
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    ABSTRACT: Centrioles are essential for cilia and centrosome assembly. In centriole-containing cells, centrioles always form juxtaposed to pre-existing ones, motivating a century-old debate on centriole biogenesis control. Here, we show that trans-autoactivation of Polo-like kinase 4 (PLK4), the trigger of centriole biogenesis, is a critical event in the spatial control of that process. We demonstrate that centrioles promote PLK4 activation through its recruitment and local accumulation. Though centriole removal reduces the proportion of active PLK4, this is rescued by concentrating PLK4 to the peroxisome lumen. Moreover, while mild overexpression of PLK4 only triggers centriole amplification at the existing centriole, higher PLK4 levels trigger both centriolar and cytoplasmatic (de novo) biogenesis. Hence, centrioles promote their assembly locally and disfavor de novo synthesis. Similar mechanisms enforcing the local concentration and/or activity of other centriole components are likely to contribute to the spatial control of centriole biogenesis under physiological conditions.
    Full-text · Article · Oct 2015 · Developmental Cell
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    • "The association of MCPH proteins with the centrosome is evolutionarily conserved with Caenorhabditis elegans (Delattre et al., 2006; Strnad and Gonczy, 2008). Three MCPH proteins, CEP152, CEP135 and STIL, interact with and promote the centrosomal localization of SAS4 (also known as CPAP or CENPJ) (Strnad and Gonczy, 2008; Cizmecioglu et al., 2010; Dzhindzhev et al., 2010; Sir et al., 2011; Brown et al., 2013; Lin et al., 2013). Failure to recruit SAS4 can attenuate centriole elongation and duplication (Schmidt et al., 2009; Comartin et al., 2013; Lin et al., 2013). "
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