The centriolar satellite proteins Cep72 and Cep290 interact and are required for recruitment of BBS proteins to the cilium

Stowe, Timothy R.; Wilkinson, C. D. W.; Iqbal, Anila; Stearns, Tim

doi:10.1091/mbc.e12-02-0134

Cited by 130 publications

(214 citation statements)

References 59 publications

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“…Proteins that, putatively, interacted with Ccdc13 with the greatest peptide coverage were PCM1, pericentrin, Cep290, Cep215, Cep131, Cep90 and Cep72 (Fig. 3A), which have all been previously shown to localise to centriolar satellites (Balczon et al, 1994;Dammermann and Merdes, 2002;Kim et al, 2008;Kim et al, 2012;Lee and Rhee, 2010;Lopes et al, 2011;Ma and Jarman, 2011;Stowe et al, 2012). Additionally, we confirmed that YFP-Ccdc13 colocalised with PCM1 and pericentrin (Fig.…”

Section: Ccdc13 Is a Novel Human Centriolar Satellite Proteinsupporting

confidence: 81%

“…A number of centriolar satellite proteins, such as PCM1 and the ciliopathy proteins Cep290 and Bardet-Biedl syndrome protein 4 (BBS4) cooperate in the formation of the primary cilia (Kim et al, 2008;Lopes et al, 2011;Stowe et al, 2012), an organelle that has only recently been appreciated as a crucial signalling hub for a number of pathways, which include Wnt and sonic hedgehog (Logan et al, 2011). Recent work has demonstrated that a number of proteins involved in the DNA damage response (DDR) also function during ciliogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Ccdc13; a novel human centriolar satellite protein required for ciliogenesis and genome stability

Staples

Myers

Beveridge

et al. 2014

Journal of Cell Science

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Here, we identify coiled-coil domain-containing protein 13 (Ccdc13) in a genome-wide RNA interference screen for regulators of genome stability. We establish that Ccdc13 is a newly identified centriolar satellite protein that interacts with PCM1, Cep290 and pericentrin and prevents the accumulation of DNA damage during mitotic transit. Depletion of Ccdc13 results in the loss of microtubule organisation in a manner similar to PCM1 and Cep290 depletion, although Ccdc13 is not required for satellite integrity. We show that microtubule regrowth is enhanced in Ccdc13-depleted cells, but slowed in cells that overexpress Ccdc13. Furthermore, in serumstarved cells, Ccdc13 localises to the basal body, is required for primary cilia formation and promotes the localisation of the ciliopathy protein BBS4 to both centriolar satellites and cilia. These data highlight the emerging link between DNA damage response factors, centriolar and peri-centriolar satellites and ciliaassociated proteins and implicate Ccdc13 as a centriolar satellite protein that functions to promote both genome stability and cilia formation.

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Section: Ccdc13 Is a Novel Human Centriolar Satellite Proteinsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Ccdc13; a novel human centriolar satellite protein required for ciliogenesis and genome stability

Staples

Myers

Beveridge

et al. 2014

Journal of Cell Science

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“…Centriolar satellites have been implicated in centrosomal protein transport and ciliogenesis [118]. In addition to providing a platform for pro-ciliogenesis proteins, satellites suppress untimely cilia formation by sequestering key ciliogenesis factors [115,[119][120][121][122]. Thus, certain ciliopathy phenotypes could arise from ill-timed ciliogenesis and signalling.…”

Section: Ciliopathies (A) Primary Cilia Formation and Centriolar Satementioning

confidence: 99%

“…First, evidence suggests that hypomorphic mutations target specific aspects of protein function [126]. Second, CEP290 and OFD1 participate in multiple protein complexes during ciliogenesis, which could be differentially affected by mutations [122,123,126,143]. Last, patients often carry mutations in multiple ciliary genes [116].…”

Section: Ciliopathies (A) Primary Cilia Formation and Centriolar Satementioning

confidence: 99%

Small organelle, big responsibility: the role of centrosomes in development and disease

Chavali

Pütz

Gergely

2014

Phil. Trans. R. Soc. B

137

111

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The centrosome, a key microtubule organizing centre, is composed of centrioles, embedded in a protein-rich matrix. Centrosomes control the internal spatial organization of somatic cells, and as such contribute to cell division, cell polarity and migration. Upon exiting the cell cycle, most cell types in the human body convert their centrioles into basal bodies, which drive the assembly of primary cilia, involved in sensing and signal transduction at the cell surface. Centrosomal genes are targeted by mutations in numerous human developmental disorders, ranging from diseases exclusively affecting brain development, through global growth failure syndromes to diverse pathologies associated with ciliary malfunction. Despite our much-improved understanding of centrosome function in cellular processes, we know remarkably little of its role in the organismal context, especially in mammals. In this review, we examine how centrosome dysfunction impacts on complex physiological processes and speculate on the challenges we face when applying knowledge generated from in vitro and in vivo model systems to human development.

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“…Immunostaining, using ARL13B and gamma-tubulin antibodies, revealed significantly longer cilia in Cdk10KO MEFs than in WT cells ( Figures 3F and 3G), corroborating results that were reported after the silencing of Cdk10 or cyclin M by siRNA 10 (for a review, see Guen et al 33 ). BBS4, which interacts with CEP290, 34 is a BBSome component that is essential for cilia formation, 35 providing a rationale for our observation of longer cilia in Cdk10KO MEFs.…”

Section: Mice With Mutant Cdk10 Display Defects In Multiple Organsmentioning

confidence: 75%

CDK10 Mutations in Humans and Mice Cause Severe Growth Retardation, Spine Malformations, and Developmental Delays

Windpassinger

Piard

Bonnard

et al. 2017

The American Journal of Human Genetics

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In five separate families, we identified nine individuals affected by a previously unidentified syndrome characterized by growth retardation, spine malformation, facial dysmorphisms, and developmental delays. Using homozygosity mapping, array CGH, and exome sequencing, we uncovered bi-allelic loss-of-function CDK10 mutations segregating with this disease. CDK10 is a protein kinase that partners with cyclin M to phosphorylate substrates such as ETS2 and PKN2 in order to modulate cellular growth. To validate and model the pathogenicity of these CDK10 germline mutations, we generated conditional-knockout mice. Homozygous Cdk10-knockout mice died postnatally with severe growth retardation, skeletal defects, and kidney and lung abnormalities, symptoms that partly resemble the disease's effect in humans. Fibroblasts derived from affected individuals and Cdk10-knockout mouse embryonic fibroblasts (MEFs) proliferated normally; however, Cdk10-knockout MEFs developed longer cilia. Comparative transcriptomic analysis of mutant and wild-type mouse organs revealed lipid metabolic changes consistent with growth impairment and altered ciliogenesis in the absence of CDK10. Our results document the CDK10 loss-of-function phenotype and point to a function for CDK10 in transducing signals received at the primary cilia to sustain embryonic and postnatal development.

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The centriolar satellite proteins Cep72 and Cep290 interact and are required for recruitment of BBS proteins to the cilium

Cited by 130 publications

References 59 publications

Ccdc13; a novel human centriolar satellite protein required for ciliogenesis and genome stability

Ccdc13; a novel human centriolar satellite protein required for ciliogenesis and genome stability

Small organelle, big responsibility: the role of centrosomes in development and disease

CDK10 Mutations in Humans and Mice Cause Severe Growth Retardation, Spine Malformations, and Developmental Delays

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