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ZMYND10 functions in a chaperone relay during axonemal dynein assembly

Authors :
Girish R Mali
Patricia L Yeyati
Seiya Mizuno
Daniel O Dodd
Peter A Tennant
Margaret A Keighren
Petra zur Lage
Amelia Shoemark
Amaya Garcia-Munoz
Atsuko Shimada
Hiroyuki Takeda
Frank Edlich
Satoru Takahashi
Alex von Kreigsheim
Andrew P Jarman
Pleasantine Mill
Source :
eLife, Vol 7 (2018)
Publication Year :
2018
Publisher :
eLife Sciences Publications Ltd, 2018.

Abstract

Molecular chaperones promote the folding and macromolecular assembly of a diverse set of ‘client’ proteins. How ubiquitous chaperone machineries direct their activities towards specific sets of substrates is unclear. Through the use of mouse genetics, imaging and quantitative proteomics we uncover that ZMYND10 is a novel co-chaperone that confers specificity for the FKBP8-HSP90 chaperone complex towards axonemal dynein clients required for cilia motility. Loss of ZMYND10 perturbs the chaperoning of axonemal dynein heavy chains, triggering broader degradation of dynein motor subunits. We show that pharmacological inhibition of FKBP8 phenocopies dynein motor instability associated with the loss of ZMYND10 in airway cells and that human disease-causing variants of ZMYND10 disrupt its ability to act as an FKBP8-HSP90 co-chaperone. Our study indicates that primary ciliary dyskinesia (PCD), caused by mutations in dynein assembly factors disrupting cytoplasmic pre-assembly of axonemal dynein motors, should be considered a cell-type specific protein-misfolding disease.

Details

Language :
English
ISSN :
2050084X
Volume :
7
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.27117010a0254df1a32e0270b4de8c8e
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.34389