ArticleThe Journal of biological chemistry2014
Myopathy-causing mutations in an HSP40 chaperone disrupt processing of specific client conformers.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 61 citations in OpenAlex.
- FBXL21 regulates diurnal proteostasis in skeletal muscle by targeting DNAJB6 and client proteins.EMBO reports · 2026Article
- Molecular genetics of J-domain protein-related chaperonopathies in skeletal muscle.Journal of human genetics · 2025Review
- Scouring the human Hsp70 network uncovers diverse chaperone safeguards buffering TDP-43 toxicity.bioRxiv : the preprint server for biology · 2025Article
- Hsf1 is essential for proteotoxic stress response in smyd1b-deficient embryos and fish survival under heat shock.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Genotype‒phenotype correlation in recessive DNAJB4 myopathy.Acta neuropathologica communications · 2024Article
- Mitochondrial abnormalities contribute to muscle weakness in a Dnajb6 deficient zebrafish model.Human molecular genetics · 2024Article
- Tertiary structure and conformational dynamics of the anti-amyloidogenic chaperone DNAJB6b at atomistic resolution.Nature communications · 2024Article
- Next Generation Sequencing and Electromyography Reveal the Involvement of theCurrent issues in molecular biology · 2024Article
- DNAJB6 mutants display toxic gain of function through unregulated interaction with Hsp70 chaperones.Nature communications · 2023Article
- DNAJB6 isoform specific knockdown: Therapeutic potential for limb girdle muscular dystrophy D1.Molecular therapy. Nucleic acids · 2023Article
- LGMDD1 natural history and phenotypic spectrum: Implications for clinical trials.Annals of clinical and translational neurology · 2023Observational
- The chaperone DNAJB6 surveils FG-nucleoporins and is required for interphase nuclear pore complex biogenesis.Nature cell biology · 2022Article
- Article
- Review
- Disease-associated mutations within the yeast DNAJB6 homolog Sis1 slow conformer-specific substrate processing and can be corrected by the modulation of nucleotide exchange factors.Nature communications · 2022Article
- Case Report: A Novel Splice-Site Mutation in DNAJB6 Associated With Juvenile-Onset Proximal-Distal Myopathy in a Chinese Patient.Frontiers in genetics · 2022Article
- A novel recessive mutation affecting DNAJB6a causes myofibrillar myopathy.Acta neuropathologica communications · 2021Article
- Inhibition of DNAJ-HSP70 interaction improves strength in muscular dystrophy.The Journal of clinical investigation · 2020Article
- Nucleation seed size determines amyloid clearance and establishes a barrier to prion appearance in yeast.Nature structural & molecular biology · 2020Article
- Neuromuscular Diseases Due to Chaperone Mutations: A Review and Some New Results.International journal of molecular sciences · 2020Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The molecular chaperone network protects against the toxic misfolding and aggregation of proteins. Disruption of this network leads to a variety of protein conformational disorders. One such example recently discovered is limb-girdle muscular dystrophy type 1D (LGMD1D), which is caused by mutation of the HSP40 chaperone DNAJB6. All LGMD1D-associated mutations localize to the conserved G/F domain of DNAJB6, but the function of this domain is largely unknown. Here, we exploit the yeast HSP40 Sis1, which has known aggregation-prone client proteins, to gain insight into the role of the G/F domain and its significance in LGMD1D pathogenesis. Strikingly, we demonstrate that LGMD1D mutations in a Sis1-DNAJB6 chimera differentially impair the processing of specific conformers of two yeast prions, [RNQ+] and [PSI+]. Importantly, these differences do not simply correlate to the sensitivity of these prion strains to changes in chaperone levels. Additionally, we analyzed the effect of LGMD1D-associated DNAJB6 mutations on TDP-43, a protein known to form inclusions in LGMD1D. We show that the DNAJB6 G/F domain mutants disrupt the processing of nuclear TDP-43 stress granules in mammalian cells. These data suggest that the G/F domain mediates chaperone-substrate interactions in a manner that extends beyond recognition of a particular client and to a subset of client conformers. We propose that such selective chaperone disruption may lead to the accumulation of toxic aggregate conformers and result in the development of LGMD1D and perhaps other protein conformational disorders.
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