Cryo-electron tomography reveals ciliary defects underlying human RSPH1 primary ciliary dyskinesia

Jianfeng Lin, Weining Yin, Maria C. Smith, Kangkang Song, Margaret W. Leigh, Maimoona A. Zariwala, Michael R. Knowles, Lawrence E. Ostrowski () and Daniela Nicastro ()
Additional contact information
Jianfeng Lin: Rosenstiel Basic Medical Sciences Research Center, Brandeis University
Weining Yin: Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina
Maria C. Smith: Rosenstiel Basic Medical Sciences Research Center, Brandeis University
Kangkang Song: Rosenstiel Basic Medical Sciences Research Center, Brandeis University
Margaret W. Leigh: University of North Carolina School of Medicine
Maimoona A. Zariwala: University of North Carolina School of Medicine
Michael R. Knowles: University of North Carolina School of Medicine
Lawrence E. Ostrowski: Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina
Daniela Nicastro: Rosenstiel Basic Medical Sciences Research Center, Brandeis University

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: Abstract Cilia play essential roles in normal human development and health; cilia dysfunction results in diseases such as primary ciliary dyskinesia (PCD). Despite their importance, the native structure of human cilia is unknown, and structural defects in the cilia of patients are often undetectable or remain elusive because of heterogeneity. Here we develop an approach that enables visualization of human (patient) cilia at high-resolution using cryo-electron tomography of samples obtained noninvasively by nasal scrape biopsy. We present the native 3D structures of normal and PCD-causing RSPH1-mutant human respiratory cilia in unprecedented detail; this allows comparisons of cilia structure across evolutionarily distant species and reveals the previously unknown primary defect and the heterogeneous secondary defects in RSPH1-mutant cilia. Our data provide evidence for structural and functional heterogeneity in radial spokes, suggest a mechanism for the milder RSPH1 PCD phenotype and demonstrate that cryo-electron tomography can be applied to human disease by directly imaging patient samples.

Date: 2014
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/ncomms6727 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6727

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms6727

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().