6533b7dcfe1ef96bd1271b0b
RESEARCH PRODUCT
X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3
Chiara OlceseMitali P. PatelAmelia ShoemarkSanteri KiviluotoMarie LegendreHywel J. WilliamsCara K. VaughanJane HaywardAlice GoldenbergRichard D. EmesMustafa M. MunyeLaura DyerThomas CahillJeremy BevillardCorinne GehrigMichel GuipponiSandra ChantotPhilippe DuquesnoyLucie ThomasLudovic JeansonBruno CopinAline TamaletChristel Thauvin-robinetJean-francois PaponAntoine GarinIsabelle PinGabriella VeraPaul AuroraMahmoud R. FassadLucy JenkinsChristopher BoustredThomas CullupMellisa DixonAlexandros OnoufriadisAndrew BushEddie M. K. ChungStylianos E. AntonarakisMichael R. LoebingerRobert WilsonMiguel ArmengotEstelle EscudierClaire HoggSerge AmselemZhaoxia SunLucia BartoloniJean-louis BlouinHannah M. Mitchisonsubject
MaleCytoplasmProtein FoldingAxoneme[SDV]Life Sciences [q-bio][SDV.GEN] Life Sciences [q-bio]/Genetics[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tractouterGenes X-LinkedChilddefectsPhylogenyZebrafisharmsSequence DeletionvariantsIntracellular Signaling Peptides and ProteinsGenetic Diseases X-LinkedPedigreeMultidisciplinary Sciences[SDV] Life Sciences [q-bio]motilityChild PreschoolMicrotubule ProteinsSperm MotilityScience & Technology - Other TopicsFemaleAdultAdolescentinnerUK10K Rare Groupr2tp complexof-function mutationsArticleMicroscopy Electron TransmissionMD MultidisciplinaryExome SequencingAnimalsHumansPoint MutationCiliaHSP90 Heat-Shock Proteins[SDV.GEN]Life Sciences [q-bio]/GeneticsScience & TechnologyKartagener SyndromeInfant NewbornAxonemal DyneinsDisease Models AnimalHEK293 Cells[SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tractidentifies mutationsproteinApoptosis Regulatory ProteinsSequence AlignmentMolecular Chaperonesdescription
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 DNAAF2–DNAAF4–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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-02-01 | Nature Communications |