How does cilium length affect beating?

Bottier, Mathieu; Thomas, Kyle A.; Dutcher, Susan K.; Bayly, Philip V.

doi:10.1101/474346

Cited by 11 publications

(15 citation statements)

References 66 publications

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“…6.24±1.26μm), providing at least a partial basis for ciliary transport failure based on biophysical models for mucociliary transport which include ciliary length as a critical parameter in force generation [26][27][28] .…”

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confidence: 99%

A human ciliopathy reveals essential functions for NEK10 in airway mucociliary clearance

Chivukula

Montoro

Leung

et al. 2020

Nat Med

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Author contributions R.R.C. initiated the project, phenotyped the index proband, designed and performed all experiments except as detailed herewith, analyzed data, prepared figures, and wrote the manuscript. D.T.M assisted with designing and performing cell culture, IF, and FACS experiments, analyzed data, and edited the manuscript. H.M.L. performed μOCT experiments, analyzed data, and prepared figures. J.Y. assisted with molecular cloning, site-directed mutagenesis, and cell culture and edited the manuscript. H.E.S. performed whole exome sequencing and linkage analysis on kindreds 1-3. M.S.T. acquired clinical histopathology images and prepared figures. G.W.D. performed sequencing, molecular biology, and HSVM analysis on kindred 4. M.A.Z. led molecular analysis of kindred 5. J.C. performed and interpreted kindred 5 ciliary EM and HSVM. L.A.D. identified kindred 5 patients and provided clinical data. P.S. performed HSVM. K.E.B. and L.P.H. assisted with obtaining proband 1 clinical samples. I.A. identified bronchiectasis kindreds 2 and 3. E.M.F. assisted with analysis of phosphoproteomics data. V.V. assisted with IF experiments, analyzed data, and edited the manuscript. H.O. supervised and led kindred 4 analyses. M.R.K. supervised and led kindred 5 molecular analysis and clinical phenotyping. G.J.T. supervised μOCT experiments and analyzed data. F.S.A. supervised whole exome sequencing and linkage analysis of kindreds 1-3, analyzed genetics data, and edited the manuscript. D.M.S. supervised the project, designed experiments, and edited the manuscript.

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confidence: 99%

A human ciliopathy reveals essential functions for NEK10 in airway mucociliary clearance

Chivukula

Montoro

Leung

et al. 2020

Nat Med

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“…Fifty movies of fap57-050; uni1 and 51 movies of fap57-706; uni1 were compared to 153 movies of uni1-2 (the wild-type group was previously described by Bottier et al . [ 71 ]) ( Fig 5A , S6 Fig ). Body motion analysis shows that both mutants have a significantly slower body rotation rate compared to wild-type cells ( Fig 5C ), which agrees with the reduced velocity.…”

Section: Resultsmentioning

confidence: 99%

“…The single mutant uni1 is considered the wild-type reference as previously published [ 70 ]. Videos were analyzed using a custom-made program written in Matlab R2016a (The Mathworks, Natick, MA, USA) previously published [ 71 ]. From each video, a sequence of 200 consecutive frames was stored in a 3D matrix of pixel intensity values.…”

Section: Methodsmentioning

confidence: 99%

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Mutation of CFAP57, a protein required for the asymmetric targeting of a subset of inner dynein arms in Chlamydomonas, causes primary ciliary dyskinesia

et al. 2020

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Primary ciliary dyskinesia (PCD) is characterized by chronic airway disease, reduced fertility, and randomization of the left/right body axis. It is caused by defects of motile cilia and sperm flagella. We screened a cohort of affected individuals that lack an obvious axonemal defect for pathogenic variants using whole exome capture, next generation sequencing, and bioinformatic analysis assuming an autosomal recessive trait. We identified one subject with an apparently homozygous nonsense variant [(c.1762C>T), p.(Arg588*)] in the uncharacterized CFAP57 gene. Interestingly, the variant results in the skipping of exon 11 (58 amino acids), which may be due to disruption of an exonic splicing enhancer. In normal human nasal epithelial cells, CFAP57 localizes throughout the ciliary axoneme. Nasal cells from the PCD patient express a shorter, mutant version of CFAP57 and the protein is not incorporated into the axoneme. The missing 58 amino acids include portions of WD repeats that may be important for loading onto the intraflagellar transport (IFT) complexes for transport or docking onto the axoneme. A reduced beat frequency and an alteration in ciliary waveform was observed. Knockdown of CFAP57 in human tracheobronchial epithelial cells (hTECs) recapitulates these findings. Phylogenetic analysis showed that CFAP57 is highly conserved in organisms that assemble motile cilia. CFAP57 is allelic with the BOP2/IDA8/ FAP57 gene identified previously in Chlamydomonas reinhardtii. Two independent, insertional fap57 Chlamydomonas mutant strains show reduced swimming velocity and altered a1111111111 a1111111111 a1111111111 a1111111111 a1111111111

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“…Studies showed that WDPCP governs ciliogenesis in Xenopus embryos [14,17] and human nasal epithelium [18]. Although short cilia might contribute to cilia beating dysfunction [30], it is still unclear whether WDPCP directly regulated the beating of cilia. To our knowledge, this is the first study of WDPCP on cilia function in human sinonasal epithelium.…”

Section: Discussionmentioning

confidence: 99%

WDPCP modulates cilia beating through MAPK/ERK pathway in chronic rhinosinusitis

Tian

Zhong

et al. 2020

Preprint

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Background: Cilia loss and dysfunction is one of the typical pathological features of chronic rhinosinusitis. Tryptophan-aspartic acid (W-D) repeat containing planar cell polarity effector (WDPCP) has been proven to be an essential element for ciliogenesis in human nasal epithelium, but its role in the beating of cilia remains unclear. Cilia beating requires energy from the mitochondria, which is regulated by the MAPK/ERK pathway. In this study, we sought to investigate the role of WDPCP and its underlying mechanism behind the dysfunction in the beating of cilia in chronic rhinosinusitis.Methods: We demonstrated WDPCP expression in the epithelium of nasal polyps. We also investigated the MAPK/ERK pathway in primary human sinonasal epithelial cells to explore the function of WDPCP. The air-liquid interface culture system was used as a model to verify the role of WDPCP and the MAPK/ERK pathway in the beating of cilia.Results: With the dysfunction of cilia beating, we observed a low expression of WDPCP in the epithelium of nasal polyps. Within the in vitro study, we found that WDPCP was critical for mitochondrial biogenesis and mitochondrial function in human sinonasal epithelial cells, possibly due to the activation of the MAPK/ERK pathway. The mitochondrial dysfunction caused by U0126 or lacking WDPCP could be partially recovered by dexamethasone.Conclusion: The low expression of WDPCP in nasal epithelium could affect mitochondria via the MAPK/ERK pathway, which may contribute to the dysfunction in the beating of cilia in chronic rhinosinusitis.

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How does cilium length affect beating?

Cited by 11 publications

References 66 publications

A human ciliopathy reveals essential functions for NEK10 in airway mucociliary clearance

A human ciliopathy reveals essential functions for NEK10 in airway mucociliary clearance

Mutation of CFAP57, a protein required for the asymmetric targeting of a subset of inner dynein arms in Chlamydomonas, causes primary ciliary dyskinesia

WDPCP modulates cilia beating through MAPK/ERK pathway in chronic rhinosinusitis

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