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

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 d...

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Main Authors: Olcese, Chiara, Patel, Mitali P., Shoemark, Amelia, Kiviluoto, Santeri, Legendre, Marie, Williams, Hywel J., Vaughan, Cara K., Hayward, Jane, Goldenberg, Alice, Emes, Richard D., Munye, Mustafa M., Dyer, Laura, Cahill, Thomas, Bevillard, Jeremy, Gehrig, Corinne, Guipponi, Michel, Chantot, Sandra, Duquesnoy, Philippe, Thomas, Lucie, Jeanson, Ludovic, Copin, Bruno, Tamalet, Aline, Thauvin-Robinet, Christel, Papon, Jean- François, Garin, Antoine, Pin, Isabelle, Vera, Gabriella, Aurora, Paul, Fassad, Mahmoud R., Jenkins, Lucy, Boustred, Christopher, Cullup, Thomas, Dixon, Mellisa, Onoufriadis, Alexandros, Bush, Andrew, Chung, Eddie M. K., Antonarakis, Stylianos E., Loebinger, Michael R., Wilson, Robert, Armengot, Miguel, Escudier, Estelle, Hogg, Claire, Al-Turki, Saeed, Anderson, Carl, Antony, Dinu, Barroso, Inês, Beales, Philip L., Bentham, Jamie, Bhattacharya, Shoumo, Carss, Keren, Chatterjee, Krishna, Cirak, Sebahattin, Cosgrove, Catherine, Allan, Daly, Durbin, Richard, Fitzpatrick, David, Floyd, Jamie, Foley, A. Reghan, Franklin, Chris, Futema, Marta, Humphries, Steve E., Hurles, Matt, McCarthy, Shane, Muddyman, Dawn, Muntoni, Francesco, Parker, Victoria, Payne, Felicity, Plagnol, Vincent, Raymond, Lucy, Savage, David B., Scambler, Peter J., Schmidts, Miriam, Semple, Robert, Serra, Eva, Stalker, Jim, van Kogelenberg, Margriet, Vijayarangakannan, Parthiban, Walter, Klaudia, Amselem, Serge, Sun, Zhaoxia, Bartoloni, Lucia, Blouin, Jean-Louis, Mitchison, Hannah M.
Format: Article
Published: Nature Publishing Group 2017
Online Access:https://eprints.nottingham.ac.uk/41044/
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author Olcese, Chiara
Patel, Mitali P.
Shoemark, Amelia
Kiviluoto, Santeri
Legendre, Marie
Williams, Hywel J.
Vaughan, Cara K.
Hayward, Jane
Goldenberg, Alice
Emes, Richard D.
Munye, Mustafa M.
Dyer, Laura
Cahill, Thomas
Bevillard, Jeremy
Gehrig, Corinne
Guipponi, Michel
Chantot, Sandra
Duquesnoy, Philippe
Thomas, Lucie
Jeanson, Ludovic
Copin, Bruno
Tamalet, Aline
Thauvin-Robinet, Christel
Papon, Jean- François
Garin, Antoine
Pin, Isabelle
Vera, Gabriella
Aurora, Paul
Fassad, Mahmoud R.
Jenkins, Lucy
Boustred, Christopher
Cullup, Thomas
Dixon, Mellisa
Onoufriadis, Alexandros
Bush, Andrew
Chung, Eddie M. K.
Antonarakis, Stylianos E.
Loebinger, Michael R.
Wilson, Robert
Armengot, Miguel
Escudier, Estelle
Hogg, Claire
Al-Turki, Saeed
Anderson, Carl
Antony, Dinu
Barroso, Inês
Beales, Philip L.
Bentham, Jamie
Bhattacharya, Shoumo
Carss, Keren
Chatterjee, Krishna
Cirak, Sebahattin
Cosgrove, Catherine
Allan, Daly
Durbin, Richard
Fitzpatrick, David
Floyd, Jamie
Foley, A. Reghan
Franklin, Chris
Futema, Marta
Humphries, Steve E.
Hurles, Matt
McCarthy, Shane
Muddyman, Dawn
Muntoni, Francesco
Parker, Victoria
Payne, Felicity
Plagnol, Vincent
Raymond, Lucy
Savage, David B.
Scambler, Peter J.
Schmidts, Miriam
Semple, Robert
Serra, Eva
Stalker, Jim
van Kogelenberg, Margriet
Vijayarangakannan, Parthiban
Walter, Klaudia
Amselem, Serge
Sun, Zhaoxia
Bartoloni, Lucia
Blouin, Jean-Louis
Mitchison, Hannah M.
author_facet Olcese, Chiara
Patel, Mitali P.
Shoemark, Amelia
Kiviluoto, Santeri
Legendre, Marie
Williams, Hywel J.
Vaughan, Cara K.
Hayward, Jane
Goldenberg, Alice
Emes, Richard D.
Munye, Mustafa M.
Dyer, Laura
Cahill, Thomas
Bevillard, Jeremy
Gehrig, Corinne
Guipponi, Michel
Chantot, Sandra
Duquesnoy, Philippe
Thomas, Lucie
Jeanson, Ludovic
Copin, Bruno
Tamalet, Aline
Thauvin-Robinet, Christel
Papon, Jean- François
Garin, Antoine
Pin, Isabelle
Vera, Gabriella
Aurora, Paul
Fassad, Mahmoud R.
Jenkins, Lucy
Boustred, Christopher
Cullup, Thomas
Dixon, Mellisa
Onoufriadis, Alexandros
Bush, Andrew
Chung, Eddie M. K.
Antonarakis, Stylianos E.
Loebinger, Michael R.
Wilson, Robert
Armengot, Miguel
Escudier, Estelle
Hogg, Claire
Al-Turki, Saeed
Anderson, Carl
Antony, Dinu
Barroso, Inês
Beales, Philip L.
Bentham, Jamie
Bhattacharya, Shoumo
Carss, Keren
Chatterjee, Krishna
Cirak, Sebahattin
Cosgrove, Catherine
Allan, Daly
Durbin, Richard
Fitzpatrick, David
Floyd, Jamie
Foley, A. Reghan
Franklin, Chris
Futema, Marta
Humphries, Steve E.
Hurles, Matt
McCarthy, Shane
Muddyman, Dawn
Muntoni, Francesco
Parker, Victoria
Payne, Felicity
Plagnol, Vincent
Raymond, Lucy
Savage, David B.
Scambler, Peter J.
Schmidts, Miriam
Semple, Robert
Serra, Eva
Stalker, Jim
van Kogelenberg, Margriet
Vijayarangakannan, Parthiban
Walter, Klaudia
Amselem, Serge
Sun, Zhaoxia
Bartoloni, Lucia
Blouin, Jean-Louis
Mitchison, Hannah M.
author_sort Olcese, Chiara
building Nottingham Research Data Repository
collection Online Access
description 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.
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institution University of Nottingham Malaysia Campus
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publisher Nature Publishing Group
recordtype eprints
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spelling nottingham-410442020-05-04T18:35:37Z https://eprints.nottingham.ac.uk/41044/ X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3 Olcese, Chiara Patel, Mitali P. Shoemark, Amelia Kiviluoto, Santeri Legendre, Marie Williams, Hywel J. Vaughan, Cara K. Hayward, Jane Goldenberg, Alice Emes, Richard D. Munye, Mustafa M. Dyer, Laura Cahill, Thomas Bevillard, Jeremy Gehrig, Corinne Guipponi, Michel Chantot, Sandra Duquesnoy, Philippe Thomas, Lucie Jeanson, Ludovic Copin, Bruno Tamalet, Aline Thauvin-Robinet, Christel Papon, Jean- François Garin, Antoine Pin, Isabelle Vera, Gabriella Aurora, Paul Fassad, Mahmoud R. Jenkins, Lucy Boustred, Christopher Cullup, Thomas Dixon, Mellisa Onoufriadis, Alexandros Bush, Andrew Chung, Eddie M. K. Antonarakis, Stylianos E. Loebinger, Michael R. Wilson, Robert Armengot, Miguel Escudier, Estelle Hogg, Claire Al-Turki, Saeed Anderson, Carl Antony, Dinu Barroso, Inês Beales, Philip L. Bentham, Jamie Bhattacharya, Shoumo Carss, Keren Chatterjee, Krishna Cirak, Sebahattin Cosgrove, Catherine Allan, Daly Durbin, Richard Fitzpatrick, David Floyd, Jamie Foley, A. Reghan Franklin, Chris Futema, Marta Humphries, Steve E. Hurles, Matt McCarthy, Shane Muddyman, Dawn Muntoni, Francesco Parker, Victoria Payne, Felicity Plagnol, Vincent Raymond, Lucy Savage, David B. Scambler, Peter J. Schmidts, Miriam Semple, Robert Serra, Eva Stalker, Jim van Kogelenberg, Margriet Vijayarangakannan, Parthiban Walter, Klaudia Amselem, Serge Sun, Zhaoxia Bartoloni, Lucia Blouin, Jean-Louis Mitchison, Hannah M. 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. Nature Publishing Group 2017-02-08 Article PeerReviewed Olcese, Chiara, Patel, Mitali P., Shoemark, Amelia, Kiviluoto, Santeri, Legendre, Marie, Williams, Hywel J., Vaughan, Cara K., Hayward, Jane, Goldenberg, Alice, Emes, Richard D., Munye, Mustafa M., Dyer, Laura, Cahill, Thomas, Bevillard, Jeremy, Gehrig, Corinne, Guipponi, Michel, Chantot, Sandra, Duquesnoy, Philippe, Thomas, Lucie, Jeanson, Ludovic, Copin, Bruno, Tamalet, Aline, Thauvin-Robinet, Christel, Papon, Jean- François, Garin, Antoine, Pin, Isabelle, Vera, Gabriella, Aurora, Paul, Fassad, Mahmoud R., Jenkins, Lucy, Boustred, Christopher, Cullup, Thomas, Dixon, Mellisa, Onoufriadis, Alexandros, Bush, Andrew, Chung, Eddie M. K., Antonarakis, Stylianos E., Loebinger, Michael R., Wilson, Robert, Armengot, Miguel, Escudier, Estelle, Hogg, Claire, Al-Turki, Saeed, Anderson, Carl, Antony, Dinu, Barroso, Inês, Beales, Philip L., Bentham, Jamie, Bhattacharya, Shoumo, Carss, Keren, Chatterjee, Krishna, Cirak, Sebahattin, Cosgrove, Catherine, Allan, Daly, Durbin, Richard, Fitzpatrick, David, Floyd, Jamie, Foley, A. Reghan, Franklin, Chris, Futema, Marta, Humphries, Steve E., Hurles, Matt, McCarthy, Shane, Muddyman, Dawn, Muntoni, Francesco, Parker, Victoria, Payne, Felicity, Plagnol, Vincent, Raymond, Lucy, Savage, David B., Scambler, Peter J., Schmidts, Miriam, Semple, Robert, Serra, Eva, Stalker, Jim, van Kogelenberg, Margriet, Vijayarangakannan, Parthiban, Walter, Klaudia, Amselem, Serge, Sun, Zhaoxia, Bartoloni, Lucia, 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 http://www.nature.com/articles/ncomms14279 doi:10.1038/ncomms14279 doi:10.1038/ncomms14279
spellingShingle Olcese, Chiara
Patel, Mitali P.
Shoemark, Amelia
Kiviluoto, Santeri
Legendre, Marie
Williams, Hywel J.
Vaughan, Cara K.
Hayward, Jane
Goldenberg, Alice
Emes, Richard D.
Munye, Mustafa M.
Dyer, Laura
Cahill, Thomas
Bevillard, Jeremy
Gehrig, Corinne
Guipponi, Michel
Chantot, Sandra
Duquesnoy, Philippe
Thomas, Lucie
Jeanson, Ludovic
Copin, Bruno
Tamalet, Aline
Thauvin-Robinet, Christel
Papon, Jean- François
Garin, Antoine
Pin, Isabelle
Vera, Gabriella
Aurora, Paul
Fassad, Mahmoud R.
Jenkins, Lucy
Boustred, Christopher
Cullup, Thomas
Dixon, Mellisa
Onoufriadis, Alexandros
Bush, Andrew
Chung, Eddie M. K.
Antonarakis, Stylianos E.
Loebinger, Michael R.
Wilson, Robert
Armengot, Miguel
Escudier, Estelle
Hogg, Claire
Al-Turki, Saeed
Anderson, Carl
Antony, Dinu
Barroso, Inês
Beales, Philip L.
Bentham, Jamie
Bhattacharya, Shoumo
Carss, Keren
Chatterjee, Krishna
Cirak, Sebahattin
Cosgrove, Catherine
Allan, Daly
Durbin, Richard
Fitzpatrick, David
Floyd, Jamie
Foley, A. Reghan
Franklin, Chris
Futema, Marta
Humphries, Steve E.
Hurles, Matt
McCarthy, Shane
Muddyman, Dawn
Muntoni, Francesco
Parker, Victoria
Payne, Felicity
Plagnol, Vincent
Raymond, Lucy
Savage, David B.
Scambler, Peter J.
Schmidts, Miriam
Semple, Robert
Serra, Eva
Stalker, Jim
van Kogelenberg, Margriet
Vijayarangakannan, Parthiban
Walter, Klaudia
Amselem, Serge
Sun, Zhaoxia
Bartoloni, Lucia
Blouin, Jean-Louis
Mitchison, Hannah M.
X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3
title X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3
title_full X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3
title_fullStr X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3
title_full_unstemmed X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3
title_short X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3
title_sort x-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor pih1d3
url https://eprints.nottingham.ac.uk/41044/
https://eprints.nottingham.ac.uk/41044/
https://eprints.nottingham.ac.uk/41044/