ArticleThe EMBO journal2016
DnaJ/Hsc70 chaperone complexes control the extracellular release of neurodegenerative-associated proteins.
Article in The EMBO journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
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Who cites it
127 citing papers in PubMed, 206 citations in OpenAlex.
- Decode the Ubiquitinome in Parkinson's Disease: From Pathological Aggregates to Targeted DUB Therapeutics.Neuroscience bulletin · 2026Review
- Glycoprotein-induced phase separation drives unconventional secretion of galectin-3.Nature communications · 2026Article
- TDP43 and hnRNP K Regulate Alternative Splicing of DNAJC5.Cell biology international · 2026Article
- Extracellular Protein Quality Control in Tau Pathology.Molecular neurobiology · 2026Review
- A J-domain protein enhances memory by promoting physiological amyloid formation inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Rsp5/NEDD4 and ESCRT regulate TDP-43 toxicity and turnover via an endolysosomal clearance mechanism.The Journal of cell biology · 2026Article
- DNAJC12 Disease: Clinical Spectrum and Long-Term Outcomes.Neurology. Genetics · 2026Article
- ABCA1 Transporter Is Involved in the Secretion of CuZn Superoxide Dismutase (SOD)-1 by Activated Human T Lymphocytes.Antioxidants (Basel, Switzerland) · 2025Article
- DnaJB1 chaperone inhibits tau aggregation by recognizing its N-terminus.bioRxiv : the preprint server for biology · 2025Article
- DNAJC5 promotes cisplatin resistance in epithelial ovarian cancer by autophagy induced by the BiP/IRE1α/XBP1 endoplasmic reticulum stress pathway.Scientific reports · 2025Article
- Beyond the Secretory Pathway: New Insights Into Protein Release.Traffic (Copenhagen, Denmark) · 2025Review
- CHIP protects lysosomes from CLN4 mutant-induced membrane damage.Nature cell biology · 2025Article
- Neuronal lipofuscinosis caused by Kufs disease/CLN4 DNAJC5 mutations but not by a CSPα/DNAJC5 deficiency.Science advances · 2025Article
- Multimodal spatial gradients to explain regional susceptibility to fibrillar tau in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Targeted protein degradation with bifunctional molecules as a novel therapeutic modality for Alzheimer's disease & beyond.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Enhanced secretion of the amyotrophic lateral sclerosis ALS-associated misfolded TDP-43 mediated by the ER-ubiquitin specific peptidase USP19.Cellular and molecular life sciences : CMLS · 2025Article
- Identification of Lipophagy-Related Gene Signature for Diagnosis and Risk Prediction of Alzheimer's Disease.Biomedicines · 2025Article
- Dnajc5b contributes to male fertility by maintaining the mitochondrial functions and autophagic homeostasis during spermiogenesis.Cellular and molecular life sciences : CMLS · 2025Article
- Cysteine string protein α and a link between rare and common neurodegenerative dementias.NPJ dementia · 2025Review
- Vesicular trafficking and cell-cell communication in neurodevelopment and neurodegeneration.Frontiers in cell and developmental biology · 2025Review
67 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
It is now known that proteins associated with neurodegenerative disease can spread throughout the brain in a prionlike manner. However, the mechanisms regulating the trans-synaptic spread propagation, including the neuronal release of these proteins, remain unknown. The interaction of neurodegenerative disease-associated proteins with the molecular chaperone Hsc70 is well known, and we hypothesized that much like disaggregation, refolding, degradation, and even normal function, Hsc70 may dictate the extracellular fate of these proteins. Here, we show that several proteins, including TDP-43, α-synuclein, and the microtubule-associated protein tau, can be driven out of the cell by an Hsc70 co-chaperone, DnaJC5. In fact, DnaJC5 overexpression induced tau release in cells, neurons, and brain tissue, but only when activity of the chaperone Hsc70 was intact and when tau was able to associate with this chaperone. Moreover, release of tau from neurons was reduced in mice lacking the DnaJC5 gene and when the complement of DnaJs in the cell was altered. These results demonstrate that the dynamics of DnaJ/Hsc70 complexes are critically involved in the release of neurodegenerative disease proteins.
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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.