Ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of left–right asymmetry

Silva, Erica; Betleja, Ewelina; John, Emily R.; Spear, Philip C.; Moresco, James J.; Zhang, Siwei; Yates, John R.; Mitchell, Brian J.; Mahjoub, Moe R.

doi:10.1091/mbc.e15-07-0474

Cited by 51 publications

(81 citation statements)

References 88 publications

(130 reference statements)

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“…S1E, Movies 1, 2), consistent with the localization of endogenous CCDC66. Such dynamic behavior is similar to the localization of other satellite proteins including CEP290, CCDC11, FOP (also known as FGFR1OP) and CCDC13 (Kim et al, 2008;Lee and Stearns, 2013;Silva et al, 2016;Staples et al, 2014).…”

Section: Proximity Mapping Identifies New Centriolar Satellite Proteinsmentioning

confidence: 55%

The centriolar satellite protein CCDC66 interacts with CEP290 and functions in cilium formation and trafficking

Conkar

Culfa

Odabasi

et al. 2017

Journal of Cell Science

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Centriolar satellites are membrane-less structures that localize and move around the centrosome and cilium complex in a microtubuledependent manner. They play important roles in centrosome-and cilium-related processes, including protein trafficking to the centrosome and cilium complex, and ciliogenesis, and they are implicated in ciliopathies. Despite the important regulatory roles of centriolar satellites in the assembly and function of the centrosome and cilium complex, the molecular mechanisms of their functions remain poorly understood. To dissect the mechanism for their regulatory roles during ciliogenesis, we performed an analysis to determine the proteins that localize in close proximity to the satellite protein CEP72, among which was the retinal degeneration gene product CCDC66. We identified CCDC66 as a microtubuleassociated protein that dynamically localizes to the centrosome, centriolar satellites and the primary cilium throughout the cell cycle. Like the BBSome component BBS4, CCDC66 distributes between satellites and the primary cilium during ciliogenesis. CCDC66 has extensive proximity interactions with centrosome and centriolar satellite proteins, and co-immunoprecipitation experiments revealed interactions between CCDC66, CEP290 and PCM1. Ciliogenesis, ciliary recruitment of BBS4 and centriolar satellite organization are impaired in cells depleted for CCDC66. Taken together, our findings identify CCDC66 as a targeting factor for centrosome and cilium proteins.

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Section: Proximity Mapping Identifies New Centriolar Satellite Proteinsmentioning

confidence: 55%

The centriolar satellite protein CCDC66 interacts with CEP290 and functions in cilium formation and trafficking

Conkar

Culfa

Odabasi

et al. 2017

Journal of Cell Science

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“…All experiments performed with NIH3t3 cells were repeated at least three times with the same experimental outcome. Multiciliated mouse tracheal epithelial cells (MTECs) were isolated, cultured and differentiated as previously described in details [32, 51]. Briefly, trachea were excised from adult C57BL/6J mice, opened longitudinally to expose the lumen, and placed in 1.5 mg/ml pronase E (Sigma-Aldrich) in F12K nutrient mixture (ThermoFisher) at 4°C overnight.…”

Section: Star Methodsmentioning

confidence: 99%

Multiple Isoforms of Nesprin1 Are Integral Components of Ciliary Rootlets

et al. 2017

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SUMMARY SYNE1 (Synaptic nuclear envelope 1) encodes multiple isoforms of Nesprin1 (Nuclear Envelope Spectrin 1) that associate with the nuclear envelope (NE) through a C-terminal KASH (Klarsicht/Anc1/Syne homology) domain (Figure 1A) [1–4]. This domain interacts directly with the SUN (Sad1/Unc84) domain of Sun proteins [5–7], a family of transmembrane proteins of the inner nuclear membrane (INM) [8, 9], to form the so-called LINC complexes (Linkers of the Nucleoskeleton and the Cytoskeleton) that span the whole NE and mediate nuclear positioning [10–12]. In a stark departure from this classical depiction of Nesprin1 in the context of the NE, we report that rootletin recruits Nesprin1α at the ciliary rootlets of photoreceptors and identified asymmetric NE aggregates of Nesprin1α and Sun2 that dock filaments of rootletin at the nuclear surface. In NIH3t3 cells, we show that recombinant rootletin filaments also dock to the NE through the specific recruitment of a ~600 kDa endogenous isoform of Nesprin1 (Nes1600kDa) and of Sun2. In agreement with the association of Nesprin1α with photoreceptor ciliary rootlets and the functional interaction between rootletin and Nesprin1 in fibroblasts, we demonstrate that multiple isoforms of Nesprin1 are integral components of ciliary rootlets of multiciliated ependymal and tracheal cells. Together, these data provide a novel functional paradigm for Nesprin1 at ciliary rootlets and suggest that the wide spectrum of human pathologies linked to truncating mutations of SYNE1 [13–15] may in part originate from ciliary defects.

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“…Various centrosomal and ciliary proteins partially localize to these regions, which are found near centrosomes or basal bodies 89 . Like OFD1 and C2CD3, many centriolar satellite proteins are essential for cilium formation 89–91 . However, it remains unclear whether such proteins simply localize within the centriolar satellites before their transit to other locations that are directly relevant to ciliogenesis.…”

Section: Early Ciliogenis Is Linked To Ciliopathiesmentioning

confidence: 99%

Genes and molecular pathways underpinning ciliopathies

Reiter

Leroux

2017

Nat Rev Mol Cell Biol

1,286

1,237

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Motile and non-motile (primary) cilia are nearly ubiquitous cellular organelles. The dysfunction of cilia causes diseases known as ciliopathies. The number of reported ciliopathies (currently 35) is increasing, as is the number of established (187) and candidate (241) ciliopathy-associated genes. The characterization of ciliopathy-associated proteins and phenotypes has improved our knowledge of ciliary functions. In particular, investigating ciliopathies has helped us to understand the molecular mechanisms by which the cilium-associated basal body functions in early ciliogenesis, as well as how the transition zone functions in ciliary gating, and how intraflagellar transport enables cargo trafficking and signalling. Both basic biological and clinical studies are uncovering novel ciliopathies and the ciliary proteins involved. The assignment of these proteins to different ciliary structures, processes and ciliopathy subclasses (first order and second order) provides insights into how this versatile organelle is built, compartmentalized and functions in diverse ways that are essential for human health.

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Ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of left–right asymmetry

Cited by 51 publications

References 88 publications

The centriolar satellite protein CCDC66 interacts with CEP290 and functions in cilium formation and trafficking

The centriolar satellite protein CCDC66 interacts with CEP290 and functions in cilium formation and trafficking

Multiple Isoforms of Nesprin1 Are Integral Components of Ciliary Rootlets

Genes and molecular pathways underpinning ciliopathies

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