Resting cells rely on the DNA helicase component MCM2 to build cilia

Tena, Teresa Casar; Maerz, Lars; Szafranski, Karol; Groth, Marco; Blätte, Tamara J.; Donow, Cornelia; Matysik, Sabrina; Walther, Paul; Jeggo, Penelope A.; Burkhalter, Martin D.; Philipp, Melanie

doi:10.1093/nar/gky945

Cited by 22 publications

(25 citation statements)

References 95 publications

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“…Interestingly, ATR is also required during DNA replication, particularly for progression of stalled forks 43 and appears to have additional functions on ciliogenesis. Such non-canonical function in non-replicating cells has been also observed for components of the MCM complex, which functions as the unwinding helicase during DNA replication, but appears to govern faithful ciliogenesis in quiescent cells 44.…”

Section: Discussionmentioning

confidence: 72%

Analysis of cilia dysfunction phenotypes in zebrafish embryos depleted of Origin recognition complex factors

et al. 2019

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Meier-Gorlin syndrome (MGS) is a rare, congenital primordial microcephalic dwarfism disorder. MGS is caused by genetic variants of components of the origin recognition complex (ORC) consisting of ORC1-6 and the pre-replication complex, which together enable origin firing and hence genome replication. In addition, ORC1 has previously been shown to play a role in ciliogenesis. Here, we extend this work and investigate the function of ORC1 and two other members of the complex on cilia at an organismal level. Knockdown experiments in zebrafish confirmed the impact of ORC1 on cilia. ORC1-deficiency confers defects anticipated to arise from impaired cilia function such as formation of oedema, kidney cysts, curved bodies and left-right asymmetry defects. We found ORC1 furthermore required for cilium formation in zebrafish and demonstrate that ciliopathy phenotypes in ORC1-depleted zebrafish could not be rescued by reconstitution with ORC1 bearing a genetic variant previously identified in MGS patients. Loss-of-function of Orc4 and Orc6, respectively, conferred similar ciliopathy phenotypes and cilium shortening in zebrafish, suggesting that several, if not all, components of the ORC regulate ciliogenesis downstream to or in addition to their canonical function in replication initiation. This study presents the first in vivo evidence of an influence of the MGS genes of the ORC family on cilia, and consolidates the possibility that cilia dysfunction could contribute to the clinical manifestation of ORC-deficient MGS.

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Section: Discussionmentioning

confidence: 72%

Analysis of cilia dysfunction phenotypes in zebrafish embryos depleted of Origin recognition complex factors

et al. 2019

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“…Functions of MCM proteins outside of replication are known within Metazoa. For example, a paralog of MCM-3, the MCM2 protein, is required for normal cilia function during Zebrafish development [48] and is enriched in sensory ciliated hair cells of the inner ear [49]. Mutations in human MCM2 are associated with autosomal dominant deafness.…”

Section: Main Textmentioning

confidence: 99%

Tracking extracellular vesicle (EV) cargo as a platform for studying EVomics, signaling, and targeting in vivo

Nikonorova

Wang

Cope

et al. 2021

Preprint

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Extracellular vesicle (EV)-based signaling is a challenge to study, due to EV small size, heterogeneity, and limited information on cargo content in vivo. We present Caenorhabditis elegans as a discovery platform that allows single EV tracking from source to target tissue in living animals. We enriched ciliary EVs using GFP-tagged PKD-2 cargo followed by mass spectrometry analysis to identify 2,888 cargo candidates. By integrating our dataset with single-cell transcriptomic data, we identified EV cargo produced by individual neurons and other cell and tissue types. A single cilium produces multiple EVs with distinct protein content. Ciliary EVs carry nucleic acid binding proteins. We observed transfer of EV cargo from the male reproductive tract to the hermaphrodite uterus during mating, a direct demonstration of animal-to-animal EV targeting.

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“…IFT is involved in the tra cking of most of the proteins into the agella or cilia (46). Ciliary tra cking of proteins utilizes other proteins or complexes in association with the IFT components like BBSome complex, small GTPases like Rabs, Arfs, Arls, and ciliary components (22,(56)(57)(58). The transport of vertebrate rhodopsin to the outer segment of rod cells requires the involvement of small GTPases like Arf, Arl and Rab proteins in their vesicular targeting to the base of the inner segment (24,59).…”

Section: Discussionmentioning

confidence: 99%

SUMOylome Modulates Intraflagellar Transport Machinery and Eukaryotic Cilia Motility

Sharma¹,

Сизова²,

Pandey³

et al. 2021

Preprint

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Translocation of channelrhodopsins (ChRs) is mediated by intraflagellar transport (IFT) machinery. However, the functional role of the network containing photoreceptors, IFT and other proteins in controlling cilia motility of the alga is still not fully delineated. In the current study, we identified two important motifs at the C-terminus of ChR1. One of them is similar to a known ciliary targeting sequence that specifically interacts with a small GTPase, and the other is a SUMOylation site. For the first time, experimental data provide an insight into the role of SUMOylation in the modulation of IFT & ChR1. Blocking of SUMOylation affected the phototaxis of C. reinhardtii cells. This implies SUMOylation based regulation of protein network controlling photomotility. The conservation of SUMOylation site pattern as analyzed for the relevant photoreceptors, IFT and its associated signaling proteins in other ciliated green algae suggested SUMOylation based photobehavioural response across the microbes. This report establishes a link between evolutionary conserved SUMOylation and ciliary machinery for the maintenance and functioning of cilia across the eukaryotes. Our enriched SUMOylome of C. reinhardtii comprehends the proteins related to ciliary development and, photo-signaling, along with homologue(s) associated to human ciliopathies as SUMO targets.

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Resting cells rely on the DNA helicase component MCM2 to build cilia

Cited by 22 publications

References 95 publications

Analysis of cilia dysfunction phenotypes in zebrafish embryos depleted of Origin recognition complex factors

Analysis of cilia dysfunction phenotypes in zebrafish embryos depleted of Origin recognition complex factors

Tracking extracellular vesicle (EV) cargo as a platform for studying EVomics, signaling, and targeting in vivo

SUMOylome Modulates Intraflagellar Transport Machinery and Eukaryotic Cilia Motility

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