X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3

Olcese, Chiara and Patel, Mitali P. and Shoemark, Amelia and Kiviluoto, Santeri and Legendre, Marie and Williams, Hywel J. and Vaughan, Cara K. and Hayward, Jane and Goldenberg, Alice and Emes, Richard D. and Munye, Mustafa M. and Dyer, Laura and Cahill, Thomas and Bevillard, Jeremy and Gehrig, Corinne and Guipponi, Michel and Chantot, Sandra and Duquesnoy, Philippe and Thomas, Lucie and Jeanson, Ludovic and Copin, Bruno and Tamalet, Aline and Thauvin-Robinet, Christel and Papon, Jean- François and Garin, Antoine and Pin, Isabelle and Vera, Gabriella and Aurora, Paul and Fassad, Mahmoud R. and Jenkins, Lucy and Boustred, Christopher and Cullup, Thomas and Dixon, Mellisa and Onoufriadis, Alexandros and Bush, Andrew and Chung, Eddie M. K. and Antonarakis, Stylianos E. and Loebinger, Michael R. and Wilson, Robert and Armengot, Miguel and Escudier, Estelle and Hogg, Claire and Al-Turki, Saeed and Anderson, Carl and Antony, Dinu and Barroso, Inês and Beales, Philip L. and Bentham, Jamie and Bhattacharya, Shoumo and Carss, Keren and Chatterjee, Krishna and Cirak, Sebahattin and Cosgrove, Catherine and Allan, Daly and Durbin, Richard and Fitzpatrick, David and Floyd, Jamie and Foley, A. Reghan and Franklin, Chris and Futema, Marta and Humphries, Steve E. and Hurles, Matt and McCarthy, Shane and Muddyman, Dawn and Muntoni, Francesco and Parker, Victoria and Payne, Felicity and Plagnol, Vincent and Raymond, Lucy and Savage, David B. and Scambler, Peter J. and Schmidts, Miriam and Semple, Robert and Serra, Eva and Stalker, Jim and van Kogelenberg, Margriet and Vijayarangakannan, Parthiban and Walter, Klaudia and Amselem, Serge and Sun, Zhaoxia and Bartoloni, Lucia and Blouin, Jean-Louis and Mitchison, Hannah M. (2017) X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3. Nature Communications, 8 . p. 14279. ISSN 2041-1723

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Abstract

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.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Veterinary Medicine and Science
Identification Number: 10.1038/ncomms14279
Depositing User: Eprints, Support
Date Deposited: 03 Mar 2017 11:11
Last Modified: 13 Oct 2017 01:35
URI: http://eprints.nottingham.ac.uk/id/eprint/41044

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