Ciliopathy-associated gene Cc2d2a promotes assembly of subdistal appendages on the mother centriole during cilia biogenesis

Veleri, Shobi; Manjunath, Souparnika H.; Fariss, Robert N.; May-Simera, Helen; Brooks, Matthew; Foskett, Trevor A.; Gao, Chun; Longo, Teresa A.; Liu, Pinghu; Nagashima, Kunio; Rachel, Rivka A.; Li, Tiansen; Dong, Lijin

doi:10.1038/ncomms5207

Cited by 73 publications

(77 citation statements)

References 62 publications

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“…For example, the exocyst component Sec15 has been shown to interact with centriolin, and its depletion disrupts the organization or function of recycling endosomes at the MCs (Hehnly et al, 2012). Odf2, ninein, Cc2d2a, ε-tubulin and centriolin are core components of the SDA, and their loss leads to impaired cytoplasmic MT anchoring, disrupted recycling of endosome organization and function, and a reduced ability to form cilia (Chang et al, 2003;Dammermann and Merdes, 2002;Ishikawa et al, 2005;Veleri et al, 2014). We demonstrate in this study that cells lacking CP110 exhibit delocalization of ninein, Cc2d2a and Odf2 from basal bodies.…”

Section: Discussionmentioning

confidence: 99%

“…Embryonic fibroblasts were isolated from Cp110 +/+ , Cp110 +/− and Cp110 −/− embryos at E12.5, as described (Veleri et al, 2014). Briefly, embryos were finely minced by razor blade in a minimal amount of PBS and suspended in 1-2 ml trypsin-EDTA along with 100 Kunitz units DNase per ml/embryo and incubated with gentle shaking at 37°C for 15 min.…”

Section: Generation Of Mefsmentioning

confidence: 99%

“…Quantification of basal body-associated proteins by pixel intensity was performed as previously described (Veleri et al, 2014). Briefly, ImageJ (imagej.nih.gov/ij/) was used to quantify the pixel intensity of a defined square around the specific basal body-associated protein signal in wild-type and Cp110 −/− MEFs.…”

Section: Quantification Of Signal Intensitymentioning

confidence: 99%

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Centrosomal protein CP110 controls maturation of the mother centriole during cilia biogenesis

Yadav¹,

Sharma²,

Liu³

et al. 2016

Journal of Cell Science

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Defects in cilia centrosomal genes cause pleiotropic clinical phenotypes, collectively called ciliopathies. Cilia biogenesis is initiated by the interaction of positive and negative regulators. Centriolar coiled coil protein 110 (CP110) caps the distal end of the mother centriole and is known to act as a suppressor to control the timing of ciliogenesis. Here, we demonstrate that CP110 promotes cilia formation in vivo, in contrast to findings in cultured cells. Cp110 −/− mice die shortly after birth owing to organogenesis defects as in ciliopathies. Shh signaling is impaired in null embryos and primary cilia are reduced in multiple tissues. We show that CP110 is required for anchoring of basal bodies to the membrane during cilia formation. CP110 loss resulted in an abnormal distribution of core components of subdistal appendages (SDAs) and of recycling endosomes, which may be associated with premature extension of axonemal microtubules. Our data implicate CP110 in SDA assembly and ciliary vesicle docking, two requisite early steps in cilia formation. We suggest that CP110 has unique context-dependent functions, acting as both a suppressor and a promoter of ciliogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Generation Of Mefsmentioning

confidence: 99%

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Centrosomal protein CP110 controls maturation of the mother centriole during cilia biogenesis

Yadav¹,

Sharma²,

Liu³

et al. 2016

Journal of Cell Science

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“…Other appendage proteins have been implicated in this membrane trafficking process. For example, Cc2d2A modulates Rab8 localization and function in photoreceptor cells , suggesting a centrosome–endosome interaction. Importantly, Cc2d2A mutations are associated with the Meckel and Joubert syndromes, which are well‐known ciliopathies .…”

Section: Cilia‐independent Roles Of Cilia Proteinsmentioning

confidence: 99%

New frontiers: discovering cilia‐independent functions of cilia proteins

et al. 2015

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In most vertebrates, mitotic spindles and primary cilia arise from a common origin, the centrosome. In non-cycling cells, the centrosome is the template for primary cilia assembly and, thus, is crucial for their associated sensory and signaling functions. During mitosis, the duplicated centrosomes mature into spindle poles, which orchestrate mitotic spindle assembly, chromosome segregation, and orientation of the cell division axis. Intriguingly, both cilia and spindle poles are centrosome-based, functionally distinct structures that require the action of microtubulemediated, motor-driven transport for their assembly. Cilia proteins have been found at non-cilia sites, where they have distinct functions, illustrating a diverse and growing list of cellular processes and structures that utilize cilia proteins for crucial functions. In this review, we discuss cilia-independent functions of cilia proteins and re-evaluate their potential contributions to "cilia" disorders. See the Glossary for abbreviations used in this article. Cilia proteins and cilia disorders-is there more?Primary cilia (henceforth called "cilia") are present in almost all cell types, lymphoid cells being one exception. Thus, cilia proteins have the potential to adversely affect numerous organs and tissues when disrupted. Over the past 10-15 years, cilia loss and/or dysfunction have been linked to numerous human disorders, collectively termed ciliopathies. Phenotypes associated with cilia dysfunction are often syndromic and include cystic kidneys, polydactyly, situs inversus, obesity, and encephalocele [1], to name a few. For example, disruption of cilia-based Hedgehog (Hh) signaling has been implicated in polydactyly [2,3] and disruption of cilia-based signaling through Ca 2+ or planar cell polarity (PCP) has been linked to cystogenesis [4,5]. However, a growing body of evidence suggests that cilia proteins are, in fact, multifunctional. In addition to their localization to cilia, many localize to and are bona fide components of centrosomes, as well as other cellular organelles and structures. At these non-cilia sites, cilia proteins perform functions distinct from their ciliary roles. Thus, we contend that disruption of cilia proteins-historically named for their localization to cilia, as well as their association with cilia defects and cilia-related disorderscan additionally disrupt spindle poles and an expanding list of cellular structures that impact numerous cellular functions. As a result, it has become increasingly difficult to determine which of these cellular functions and which of the these non-cilia organelles truly contribute to ciliopathies when cilia proteins are disrupted [6,7]. In this review, we first explore the diversity of cilia-independent processes that involve cilia proteins and then discuss alternative hypotheses for the etiology of "ciliopathies".The centrosome, a common thread between cilia and mitosisMost vertebrate centrosomes are comprised of two centriole barrels surrounded by pericentriolar material (PCM). A...

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“…4 QPCR results of differential transcript expression analysis. Transcript expression levels (mean ± SD) of tektin-2 and tektin-4-like were analysed with qPCR in control (n = 6) and CO 2 stressed (n = 6) S. glomerata, and significant differences examined with a two-sample t-test assuming unequal variances (p < 0.05) hand, have both been implicated in ciliogenesis in vertebrates [121,122]. While research on the effects of stress on bivalve ciliary motility appears to be sparse, studies in M. edulis showed a decrease in ciliary activity in response to gamma radiation and loss of cilia in mussels exposed to environmental pollution [123,124].…”

Section: Ciliary Functionmentioning

confidence: 99%

Molecular analysis of the Sydney rock oyster (Saccostrea glomerata) CO2 stress response

Ertl

O’Connor

Wiegand

et al. 2016

Clim Chang Responses

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Background: Human activities have led to a substantial increase in carbon dioxide (CO 2 ) emission, with further increases predicted. A RNA-Seq study on adult Saccostrea glomerata was carried out to examine the molecular response of this bivalve species to elevated pCO 2 . Results: A total of 1626 S. glomerata transcripts were found to be differentially expressed in oysters exposed to elevated pCO 2 when compared to control oysters. These transcripts cover a range of functions, from immunity (e.g. pattern recognition receptors, antimicrobial peptides), to respiration (e.g. antioxidants, mitochondrial respiratory chain proteins) and biomineralisation (e.g. carbonic anhydrase). Overall, elevated levels of CO 2 appear to have resulted in a priming of the immune system and in producing countermeasures to potential oxidative stress. CO 2 exposure also seems to have resulted in an increase in the expression of proteins involved in protein synthesis, whereas transcripts putatively coding for proteins with a role in cilia and flagella function were down-regulated in response to the stressor. In addition, while some of the transcripts related to biomineralisation were up-regulated (e.g. carbonic anhydrase 2, alkaline phosphatase), a small group was down-regulated (e.g. perlucin). Conclusions: This study highlighted the complex molecular response of the bivalve S. glomerata to expected near-future ocean acidification levels. While there are indications that the oyster attempted to adapt to the stressor, gauged by immune system priming and the increase in protein synthesis, some processes such cilia function appear to have been negatively affected by the elevated levels of CO 2 .

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Ciliopathy-associated gene Cc2d2a promotes assembly of subdistal appendages on the mother centriole during cilia biogenesis

Cited by 73 publications

References 62 publications

Centrosomal protein CP110 controls maturation of the mother centriole during cilia biogenesis

Centrosomal protein CP110 controls maturation of the mother centriole during cilia biogenesis

New frontiers: discovering cilia‐independent functions of cilia proteins

Molecular analysis of the Sydney rock oyster (Saccostrea glomerata) CO2 stress response

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