Proximity Interactions among Centrosome Components Identify Regulators of Centriole Duplication

Fırat-Karalar, Elif Nur; Rauniyar, Navin; Yates, John R.; Stearns, Tim

doi:10.1016/j.cub.2014.01.067

Cited by 180 publications

(233 citation statements)

References 38 publications

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“…Previous research revealed that DVL localizes to centrosome (6,22), which we confirmed by endogenous immunocytochemistry and biochemical fractionation (SI Appendix, Fig. S1 A-C).…”

Section: Resultssupporting

confidence: 57%

Dishevelled is a NEK2 kinase substrate controlling dynamics of centrosomal linker proteins

Červenka

Valnohová

Bernatík

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Dishevelled (DVL) is a key scaffolding protein and a branching point in Wnt signaling pathways. Here, we present conclusive evidence that DVL regulates the centrosomal cycle. We demonstrate that DVL dishevelled and axin (DIX) domain, but not DIX domain-mediated multimerization, is essential for DVL's centrosomal localization. DVL accumulates during the cell cycle and associates with NIMA-related kinase 2 (NEK2), which is able to phosphorylate DVL at a multitude of residues, as detected by a set of novel phospho-specific antibodies. This creates interfaces for efficient binding to CDK5 regulatory subunitassociated protein 2 (CDK5RAP2) and centrosomal Nek2-associated protein 1 (C-NAP1), two proteins of the centrosomal linker. Displacement of DVL from the centrosome and its release into the cytoplasm on NEK2 phosphorylation is coupled to the removal of linker proteins, an event necessary for centrosomal separation and proper formation of the mitotic spindle. Lack of DVL prevents NEK2-controlled dissolution of loose centrosomal linker and subsequent centrosomal separation. Increased DVL levels, in contrast, sequester centrosomal NEK2 and mimic monopolar spindle defects induced by a dominant negative version of this kinase. Our study thus uncovers molecular crosstalk between centrosome and Wnt signaling.Wnt signaling | centrosome | Dishevelled | NEK2 | linker proteins

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“…Previous research revealed that DVL localizes to centrosome (6,22), which we confirmed by endogenous immunocytochemistry and biochemical fractionation (SI Appendix, Fig. S1 A-C).…”

Section: Resultssupporting

confidence: 57%

Dishevelled is a NEK2 kinase substrate controlling dynamics of centrosomal linker proteins

Červenka

Valnohová

Bernatík

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Asl also has additional roles in binding Sas-4 to help establish the PCM (see below). Cep192 also binds to Plk4 and so cooperates with Cep152 in recruiting Plk4 to the centriole (Sonnen et al 2013;Firat-Karalar et al 2014). This echoes the finding of the dependency of ZYG-1 recruitment on SPD-2 in C. elegans.…”

Section: Plk4supporting

confidence: 67%

The Centrosome and Its Duplication Cycle

Hagan

Glover

2015

Cold Spring Harb Perspect Biol

206

194

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“…Centriolar satellites are linked to several centrosome-related processes including centrosome and cilium protein trafficking, ciliogenesis and centriole duplication (Firat-Karalar et al, 2014), and are implicated in ciliopathies (Bärenz et al, 2011). CCDC113 is related to CCDC96, one of the other centrosome-localizing proteins (supplementary material Fig.…”

Section: Resultsmentioning

confidence: 99%

Proteomic analysis of mammalian sperm cells identifies new components of the centrosome

Fırat-Karalar

Sante

Elliott

et al. 2014

Journal of Cell Science

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Centrioles are evolutionarily conserved microtubule-based structures at the core of the animal centrosome that are essential for nucleating the axoneme of cilia. We hypothesized that centriole proteins have been under-represented in proteomic studies of the centrosome, because of the larger amount of pericentriolar material making up the centrosome. In this study, we have overcome this problem by determining the centriolar proteome of mammalian sperm cells, which have a pair of centrioles but little pericentriolar material. Mass spectrometry of sperm centrioles identifies known components of centrioles and many previously uncharacterized candidate centriole proteins. Assessment of localization of a subset of these candidates in cultured cells identified CCDC113, CCDC96, C4orf47, CCDC38, C7orf31, CCDC146, CCDC81 and CCDC116 as centrosome-associated proteins. We examined the highly conserved protein CCDC113 further and found that it is a component of centriolar satellites, is in a complex with the satellite proteins HAP1 and PCM1, and functions in primary cilium formation.

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Proximity Interactions among Centrosome Components Identify Regulators of Centriole Duplication

Cited by 180 publications

References 38 publications

Dishevelled is a NEK2 kinase substrate controlling dynamics of centrosomal linker proteins

Dishevelled is a NEK2 kinase substrate controlling dynamics of centrosomal linker proteins

The Centrosome and Its Duplication Cycle

Proteomic analysis of mammalian sperm cells identifies new components of the centrosome

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