Fiche publication
Date publication
février 2017
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Pr THAUVIN-ROBINET Christel
Tous les auteurs :
Olcese C, Patel MP, Shoemark A, Kiviluoto S, Legendre M, Williams HJ, Vaughan CK, Hayward J, Goldenberg A, Emes RD, Munye MM, Dyer L, Cahill T, Bevillard J, Gehrig C, Guipponi M, Chantot S, Duquesnoy P, Thomas L, Jeanson L, Copin B, Tamalet A, Thauvin-Robinet C, Papon JF, Garin A, Pin I, Vera G, Aurora P, Fassad MR, Jenkins L, Boustred C, Cullup T, Dixon M, Onoufriadis A, Bush A, Chung EM, Antonarakis SE, Loebinger MR, Wilson R, Armengot M, Escudier E, Hogg C, ,Amselem S, Sun Z, Bartoloni L, Blouin JL, Mitchison HM
Lien Pubmed
Résumé
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.
Mots clés
Adolescent, Adult, Animals, Apoptosis Regulatory Proteins, genetics, Axonemal Dyneins, metabolism, Axoneme, pathology, Child, Child, Preschool, Cilia, pathology, Cytoplasm, pathology, Disease Models, Animal, Female, Genes, X-Linked, genetics, Genetic Diseases, X-Linked, genetics, HEK293 Cells, HSP90 Heat-Shock Proteins, metabolism, Humans, Infant, Newborn, Intracellular Signaling Peptides and Proteins, Kartagener Syndrome, genetics, Male, Microscopy, Electron, Transmission, Microtubule Proteins, genetics, Molecular Chaperones, genetics, Pedigree, Phylogeny, Point Mutation, Protein Folding, Sequence Alignment, Sequence Deletion, Sperm Motility, genetics, Exome Sequencing, Zebrafish
Référence
Nat Commun. 2017 02 8;8:14279
