ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Cellular Biochemistry
Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1593810
This article is part of the Research TopicDistinct phenotype but same genotype: Hints for the diversity of phenotypes in ciliopathiesView all 3 articles
Proteomic and structural comparison between cilia from primary ciliary dyskinesia patients with a DNAH5 defect
Provisionally accepted- 1Paul Scherrer Institut (PSI), Villigen, Switzerland
- 2ETH Zürich, Zurich, Zürich, Switzerland
- 3Department of Biology, ETH Zurich, Zurich, Switzerland
- 4University of Bern, Bern, Bern, Switzerland
- 5Sankt Claraspital, Basal, Switzerland
- 6Lungen-klinik Bethanien, ZURICH, Switzerland
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Primary ciliary dyskinesia (PCD) is a genetic disorder that affects the motile cilia in various organs, leading to recurrent respiratory infections, subfertility, and laterality abnormalities. Traditional diagnostic methods include high-speed video microscopy, immunofluorescence staining, electron microscopy, and genetic screening. However, how different disease-causing variants in the same PCD gene affect clinical presentation, as well as ciliary composition and structure, is not well understood. We investigated the effect of various mutations in DNAH5, an axonemal dynein heavy chain, using mass spectrometry and cryo-electron tomography. We demonstrated differences in the axonemal composition for patients with dnah5 mutations. Furthermore, we showed that reductions in some ciliary components are patient specific. Some proteinsof them, such as KIAA1430VWA3B, KIAA1430/CFAP97, and DTHD1, were not previously recognized as components of human respiratory motile cilia. Finally, we demonstrated that some differences in protein abundance between wild-type and PCD samples can be observed in the 96-nm repeated unit of the axoneme. Our results suggest that many axonemal components are affected in the DNAH5-defective samples. Additionally, our results highlight that disparate mutations have seemingly distinctive consequences for the axonemal composition.
Keywords: primary ciliary dyskinesia, Axoneme, DNAH5, dynein, Cryo-ET, Mass Spectrometry
Received: 14 Mar 2025; Accepted: 24 Jun 2025.
Copyright: © 2025 de Ceuninck van Capelle, Luo, Leitner, Tschanz, Latzin, Ott, herren, Mueller and Ishikawa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Takashi Ishikawa, Paul Scherrer Institut (PSI), Villigen, 5232, Switzerland
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