Novel protein networks in motile cilia from human epithelial cells revealed by cryo-ET and proteomics analysis of cilia from PCD patients
- 1Paul Scherrer Institute
Abstract
In our past study on human cilia from primary ciliary dyskinesia (PCD) patients using cryo-electron tomography and mass spectrometry, defects in the DNAH5 gene were proven to cause the loss of the entire outer dynein arm along with other proteins. This phenomenon was not observed in the unicellular green alga Chlamydomonas. In this study, we examined the loss of ciliary components caused by defects in various genes, based on proteomic and structural analyses of motile cilia from multiple PCD patients. The absence of single outer arm dynein genes causes a loss or significant decrease in other inner and outer arm dyneins. Interestingly, some patients with outer dynein defects show decreased intraflagellar transport (IFT) proteins, suggesting an influence of cargo components or assembly on transport. These phenomena were not observed in Chlamydomonas, suggesting a more complex mechanism of ciliogenesis in humans despite the high similarity in the final 3D architecture of the 9+2 axoneme. Defects in certain central pair proteins unexpectedly reduced components on the doublets as well. Our results demonstrate protein-protein interactions during stages of human motile ciliogenesis that are more complex than those in unicellular organisms.
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BibTeX
@misc{capelle2026novel,
title = {{Novel protein networks in motile cilia from human epithelial cells revealed by cryo-ET and proteomics analysis of cilia from PCD patients}},
author = {C. de Ceuninck van Capelle and T. Cairoli and P. Afanasyev and Y. Li and E. Markovic and A. Jud and A. Leitner and L. Muller and T. Ishikawa},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.28.755144},
url = {https://www.biorxiv.org/content/10.64898/2026.09.28.755144v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Novel protein networks in motile cilia from human epithelial cells revealed by cryo-ET and proteomics analysis of cilia from PCD patients
AU - C. de Ceuninck van Capelle
AU - T. Cairoli
AU - P. Afanasyev
AU - Y. Li
AU - E. Markovic
AU - A. Jud
AU - A. Leitner
AU - L. Muller
AU - T. Ishikawa
PY - 2026
DA - 2026/09/28
PB - bioRxiv
DO - 10.64898/2026.09.28.755144
UR - https://www.biorxiv.org/content/10.64898/2026.09.28.755144v1
AB - In our past study on human cilia from primary ciliary dyskinesia (PCD) patients using cryo-electron tomography and mass spectrometry, defects in the DNAH5 gene were proven to cause the loss of the entire outer dynein arm along with other proteins. This phenomenon was not observed in the unicellular green alga Chlamydomonas. In this study, we examined the loss of ciliary components caused by defects in various genes, based on proteomic and structural analyses of motile cilia from multiple PCD patients. The absence of single outer arm dynein genes causes a loss or significant decrease in other inner and outer arm dyneins. Interestingly, some patients with outer dynein defects show decreased intraflagellar transport (IFT) proteins, suggesting an influence of cargo components or assembly on transport. These phenomena were not observed in Chlamydomonas, suggesting a more complex mechanism of ciliogenesis in humans despite the high similarity in the final 3D architecture of the 9+2 axoneme. Defects in certain central pair proteins unexpectedly reduced components on the doublets as well. Our results demonstrate protein-protein interactions during stages of human motile ciliogenesis that are more complex than those in unicellular organisms.
ER -