ArticleNature communications2022
Differential roles for DNAJ isoforms in HTT-polyQ and FUS aggregation modulation revealed by chaperone screens.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Chaperone-mediated remodelling of mutant huntingtin.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- The Hsp40 cochaperone DNAJC7 regulates polyglutamine aggregation and exhibits context-dependent effects on polyglycine aggregation.The Journal of biological chemistry · 2026Article
- Unveiling DNAJB12 and DNAJB14 as crucial chaperones in hepatitis B and D virus particle morphogenesis.iScience · 2026Article
- BIP orchestrates bidirectional ER protein trafficking via co-chaperone complexes.Cellular & molecular biology letters · 2026Article
- Mechanisms and regulation of the Hsp70 chaperone network.Nature reviews. Molecular cell biology · 2026Review
- Nuclear and Cytoplasmic Mouse ID Associated 1 (MIDA1) Protein Varies in Neurons and Astrocytes Across the Different Hippocampal Regions and Exhibits Age-Related Changes.Neurochemical research · 2026Article
- Functions and Synthesis of Abscisic Acid (ABA) in Humans-Insights from Computational Approaches.International journal of molecular sciences · 2025Review
- Spatial protein redistribution: wandering but not lost.Cellular and molecular life sciences : CMLS · 2025Review
- Regulation of physiological and pathological condensates by molecular chaperones.The FEBS journal · 2025Review
- Exploring Protein Misfolding in Amyotrophic Lateral Sclerosis: Structural and Functional Insights.Biomedicines · 2025Review
- Engineering a membrane protein chaperone to ameliorate the proteotoxicity of mutant huntingtin.Nature communications · 2025Article
- NRF2-mediated autophagic degradation of glycated vimentin in the skin by an elastin-derived peptide.American journal of translational research · 2025Article
- Factors affecting protein recovery during Hsp40 affinity profiling.Analytical and bioanalytical chemistry · 2024Article
- Exercise to Mitigate Cerebrovascular Aging: A Geroscience Perspective.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Review
- A transient protein folding response targets aggregation in the early phase of TDP-43-mediated neurodegeneration.Nature communications · 2024Article
- CRISPR screen for protein inclusion formation uncovers a role for SRRD in the regulation of intermediate filament dynamics and aggresome assembly.PLoS genetics · 2024Article
- Stress biology: Complexity and multifariousness in health and disease.Cell stress & chaperones · 2024Article
- J-domain proteins: From molecular mechanisms to diseases.Cell stress & chaperones · 2024Article
- Protein quality control: from molecular mechanisms to therapeutic intervention-EMBO workshop, May 21-26 2023, Srebreno, Croatia.Cell stress & chaperones · 2023Review
- Molecular Chaperones' Potential against Defective Proteostasis of Amyotrophic Lateral Sclerosis.Cells · 2023Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein aggregation is a hallmark of neurodegeneration. Here, we find that Huntington's disease-related HTT-polyQ aggregation induces a cellular proteotoxic stress response, while ALS-related mutant FUS (mutFUS) aggregation leads to deteriorated proteostasis. Further exploring chaperone function as potential modifiers of pathological aggregation in these contexts, we reveal divergent effects of naturally-occurring chaperone isoforms on different aggregate types. We identify a complex of the full-length (FL) DNAJB14 and DNAJB12, that substantially protects from mutFUS aggregation, in an HSP70-dependent manner. Their naturally-occurring short isoforms, however, do not form a complex, and lose their ability to preclude mutFUS aggregation. In contrast, DNAJB12-short alleviates, while DNAJB12-FL aggravates, HTT-polyQ aggregation. DNAJB14-FL expression increases the mobility of mutFUS aggregates, and restores the deteriorated proteostasis in mutFUS aggregate-containing cells and primary neurons. Our results highlight a maladaptive cellular response to pathological aggregation, and reveal a layer of chaperone network complexity conferred by DNAJ isoforms, in regulation of different aggregate types.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.