期刊
NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms14279
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资金
- UK PCD Family Support Group
- NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust
- Imperial College London
- National Institute of Health Research and Health Education England
- NIH [R01HL125885-01A1, R01 DK092808-01A1]
- Swiss National Science Foundation [32003B_135709]
- Milena Carvajal Pro-Kartagener Foundation of Geneva
- Ernst et Lucie Schmidheiny foundation of Geneva
- University Hospitals of Geneva
- National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust
- King's College London
- Fondation pour la Recherche Medicale [DEQ20120323689]
- Legs Poix from the Chancellerie des Universites
- National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust
- University College London
- Wellcome Trust [WT091310]
- Action Medical Research [GN2101]
- Newlife Foundation [10-11/15]
- Great Ormond Street Hospital Children's Charity
- National Institutes of Health Research (NIHR) [NIHR-HCS-P13-04-004] Funding Source: National Institutes of Health Research (NIHR)
- Swiss National Science Foundation (SNF) [32003B_135709] Funding Source: Swiss National Science Foundation (SNF)
- Action Medical Research [2101] Funding Source: researchfish
- Great Ormond Street Hospital Childrens Charity [V4515] Funding Source: researchfish
- National Institute for Health Research [NIHR-HCS-P13-04-004, NF-SI-0514-10053] Funding Source: researchfish
By moving essential body fluids and molecules, motile cilia and flagella govern respiratory mucociliary clearance, laterality determination and the transport of gametes and cerebrospinal fluid. Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder frequently caused by non-assembly of dynein arm motors into cilia and flagella axonemes. Before their import into cilia and flagella, multi-subunit axonemal dynein arms are thought to be stabilized and pre-assembled in the cytoplasm through a DNAAF2DNAAF4- HSP90 complex akin to the HSP90 co-chaperone R2TP complex. Here, we demonstrate that large genomic deletions as well as point mutations involving PIH1D3 are responsible for an X-linked form of PCD causing disruption of early axonemal dynein assembly. We propose that PIH1D3, a protein that emerges as a new player of the cytoplasmic pre-assembly pathway, is part of a complementary conserved R2TP-like HSP90 co-chaperone complex, the loss of which affects assembly of a subset of inner arm dyneins.
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