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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.
Pubmed ID: 29916806 RIS Download
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View all literature mentionsRandomized controlled trial being conducted at two clinical centers in the United States to learn more about the effects of weight loss on urinary incontinence. About 330 overweight women aged 30 or older will participate and will be followed for 18 months. Efficacy of weight reduction as a treatment for urinary incontinence will be examined at 6 months following the intensive weight control program, and the sustained impact of the intervention will be examined at 18 months. To increase the maintenance of weight reduction and facilitate evaluation of the enduring impact of weight loss on urinary incontinence, they propose to study a motivation-based weight maintenance program. At the end of the intensive weight control program, women randomized to the weight loss program will be randomized to either a 12-month skill-based maintenance intervention or to a motivation-based maintenance intervention. The maintenance interventions maximize the potential for sustained weight loss and will allow them to determine if long-term weight reduction will produce continued improvement in urinary incontinence.
View all literature mentionsA quantitative proteomics software package for analyzing large-scale mass-spectrometric data sets. It is a set of algorithms that include peak detection and scoring of peptides, mass calibration, database searches for protein identification, protein quantification, and provides summary statistics.
View all literature mentionsThis monoclonal targets Axonemal dynein intermediate chain 1
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis monoclonal targets tGFP
View all literature mentionsThis monoclonal targets Human DNAI2
View all literature mentionsThis polyclonal targets FKBP8
View all literature mentionsThis monoclonal targets LRRC50
View all literature mentionsThis polyclonal targets DNAH5 antibody produced in rabbit
View all literature mentionsThis monoclonal targets HSP90AA1, HSP90AB1, HSP90B1
View all literature mentionsThis polyclonal targets ZMYND10
View all literature mentionsThis polyclonal targets ZMYND10
View all literature mentionsThis polyclonal targets SNTN antibody produced in rabbit
View all literature mentionsThis monoclonal targets HSP90, aa 1-724
View all literature mentionsThis polyclonal targets HSP 70 (K-20)
View all literature mentionsThis monoclonal targets GRP94
View all literature mentionsThis monoclonal targets GAPDH antibody [6C5]
View all literature mentionsThis monoclonal targets gamma Tubulin
View all literature mentionsThis monoclonal targets FKBP38
View all literature mentionsThis polyclonal targets DNALI1
View all literature mentionsThis polyclonal targets DNAI2
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis monoclonal targets Tubulin Acetylated
View all literature mentionsMus musculus with name Crl:CD1(ICR) from IMSR.
View all literature mentionsCell line hTERT-RPE1 is a Telomerase immortalized cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name C3H/HeJ from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name Crl:CD1(ICR) from IMSR.
View all literature mentionsThis polyclonal targets ZMYND10
View all literature mentionsThis polyclonal targets ZMYND10
View all literature mentionsThis polyclonal targets ZMYND10
View all literature mentionsThis monoclonal targets HSP90AA1, HSP90AB1, HSP90B1
View all literature mentionsThis monoclonal targets Human DNAI2
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis polyclonal targets DNAH5 antibody produced in rabbit
View all literature mentionsThis monoclonal targets tGFP
View all literature mentionsThis polyclonal targets FKBP8
View all literature mentionsThis monoclonal targets Human DNAI2
View all literature mentionsThis monoclonal targets Axonemal dynein intermediate chain 1
View all literature mentionsThis polyclonal targets DNAH5 antibody produced in rabbit
View all literature mentionsThis monoclonal targets LRRC50
View all literature mentionsThis monoclonal targets Human DNAI2
View all literature mentionsThis monoclonal targets HSP90AA1, HSP90AB1, HSP90B1
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis monoclonal targets tGFP
View all literature mentionsThis polyclonal targets FKBP8
View all literature mentionsThis polyclonal targets ZMYND10
View all literature mentionsThis polyclonal targets ZMYND10
View all literature mentionsThis polyclonal targets DNAH5 antibody produced in rabbit
View all literature mentionsThis monoclonal targets LRRC50
View all literature mentionsThis monoclonal targets Axonemal dynein intermediate chain 1
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