Discovering Regulators of Centriole Biogenesis through siRNA-Based Functional Genomics in Human Cells

Balestra, Fernando R.; Strnad, Petr; Flückiger, Isabelle; Gönczy, Pierre

doi:10.1016/j.devcel.2013.07.009

Cited by 8 publications

(11 citation statements)

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“…This observation is consistent with a recent report showing the centriolar localization of C2cd3 (31). However, our data more accurately defines the location of C2cd3 at the level of distal appendages, which was not identified in the previous report.…”

Section: Discussionsupporting

confidence: 93%

C2cd3 is critical for centriolar distal appendage assembly and ciliary vesicle docking in mammals

Zeng

Ning

et al. 2014

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

129

153

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The primary cilium plays critical roles in vertebrate development and physiology, but the mechanisms underlying its biogenesis remain poorly understood. We investigated the molecular function of C2 calcium-dependent domain containing 3 (C2cd3), an essential regulator of primary cilium biogenesis. We show that C2cd3 is localized to the centriolar satellites in a microtubule-and Pcm1-dependent manner; however, C2cd3 is dispensable for centriolar satellite integrity. C2cd3 is also localized to the distal ends of both mother and daughter centrioles and is required for the recruitment of five centriolar distal appendage proteins: Sclt1, Ccdc41, Cep89, Fbf1, and Cep164. Furthermore, loss of C2cd3 results in failure in the recruitment of Ttbk2 to the ciliary basal body as well as the removal of Cp110 from the ciliary basal body, two critical steps in initiating ciliogenesis. C2cd3 is also required for recruiting the intraflagellar transport proteins Ift88 and Ift52 to the mother centriole. Consistent with a role in distal appendage assembly, C2cd3 is essential for ciliary vesicle docking to the mother centriole. Our results suggest that C2cd3 regulates cilium biogenesis by promoting the assembly of centriolar distal appendages critical for docking ciliary vesicles and recruiting other essential ciliogenic proteins.

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Section: Discussionsupporting

confidence: 93%

C2cd3 is critical for centriolar distal appendage assembly and ciliary vesicle docking in mammals

Zeng

Ning

et al. 2014

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

129

153

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“…These include Cep83/CCDC41 (19,30) and C2CD3 (50)(51)(52). Although a strict requirement for Cep83/CCDC41 in Cep164 localization has been questioned (30), our data clearly demonstrate that Cep164 is both necessary and sufficient for M centriole association of TTBK2, in line with a model in which Cep83/CCDC41 acts upstream of Cep164 (19).…”

Section: Discussionsupporting

confidence: 82%

Cep164 triggers ciliogenesis by recruiting Tau tubulin kinase 2 to the mother centriole

Čajánek

Nigg

2014

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

154

211

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Primary cilia play critical roles in development and disease. Their assembly is triggered by mature centrioles (basal bodies) and requires centrosomal protein 164kDa (Cep164), a component of distal appendages. Here we show that loss of Cep164 leads to early defects in ciliogenesis, reminiscent of the phenotypic consequences of mutations in TTBK2 (Tau tubulin kinase 2). We identify Cep164 as a likely physiological substrate of TTBK2 and demonstrate that Cep164 and TTBK2 form a complex. We map the interaction domains and demonstrate that complex formation is crucial for the recruitment of TTBK2 to basal bodies. Remarkably, ciliogenesis can be restored in Cep164-depleted cells by expression of chimeric proteins in which TTBK2 is fused to the C-terminal centrioletargeting domain of Cep164. These findings indicate that one of the major functions of Cep164 in ciliogenesis is to recruit active TTBK2 to centrioles. Once positioned, TTBK2 then triggers key events required for ciliogenesis, including removal of CP110 and recruitment of intraflagellar transport proteins. In addition, our data suggest that TTBK2 also acts upstream of Cep164, contributing to the assembly of distal appendages.primary cilium | centrosome

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“…The functional homologs of these five proteins are highly conserved (Fig. 4A) (Goshima et al 2007;Dobbelaere et al 2008;Balestra et al 2013). …”

Section: The Core Pathway Of Centriole Assemblymentioning

confidence: 99%

The Centrosome and Its Duplication Cycle

Hagan

Glover

2015

Cold Spring Harb Perspect Biol

203

190

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Discovering Regulators of Centriole Biogenesis through siRNA-Based Functional Genomics in Human Cells

Cited by 8 publications

References 0 publications

C2cd3 is critical for centriolar distal appendage assembly and ciliary vesicle docking in mammals

C2cd3 is critical for centriolar distal appendage assembly and ciliary vesicle docking in mammals

Cep164 triggers ciliogenesis by recruiting Tau tubulin kinase 2 to the mother centriole

The Centrosome and Its Duplication Cycle

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