Projects per year
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.
Original language | English |
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Article number | e34389 |
Number of pages | 27 |
Journal | eLIFE |
Volume | 7 |
Early online date | 19 Jun 2018 |
DOIs | |
Publication status | Published - 13 Jul 2018 |
Keywords / Materials (for Non-textual outputs)
- Journal Article
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Dive into the research topics of 'ZMYND10 functions in a chaperone relay during axonemal dynein assembly'. Together they form a unique fingerprint.Projects
- 1 Finished
Profiles
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Andrew Jarman
- Deanery of Biomedical Sciences - Personal Chair of Developmental Cell Biology
- Centre for Discovery Brain Sciences
- Edinburgh Neuroscience
Person: Academic: Research Active
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Pleasantine Mill
- MRC Human Genetics Unit
- School of Genetics and Cancer - Personal Chair of Cilia Biology
Person: Academic: Research Active , Academic: Research Active (Research Assistant)