ArticleProceedings of the National Academy of Sciences of the United States of America2015
Intercellular chaperone transmission via exosomes contributes to maintenance of protein homeostasis at the organismal level.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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Who cites it
100 citing papers in PubMed, 211 citations in OpenAlex.
- Combating ageing beyond the cell: Emerging roles of extracellular proteostasis.The FEBS journal · 2026Review
- Exosomal nanocarriers of immune fate: molecular insights into cancer immunity, pathogen defense, and emerging immunotherapies.Clinical and experimental immunology · 2026Review
- Recent insights into HSP70: proteostasis and beyond.Frontiers in molecular biosciences · 2026Review
- Pathological Insights into Neurodegenerative and Neurodevelopmental Disorders: Perspectives for the Development of Novel Treatment Approaches.CNS & neurological disorders drug targets · 2026Review
- A familial natural short sleep mutation iniScience · 2025Article
- Extracellular Vesicles in Arthropods: Biogenesis, Functions, Isolation Methods and Applications.Journal of extracellular vesicles · 2025Review
- The function of chaperones in the radioresistance of glioblastoma: a new insight into the current knowledge.Brain tumor pathology · 2025Review
- Review
- Chaperone Proteins: The Rising Players in Muscle Atrophy.Journal of cachexia, sarcopenia and muscle · 2025Review
- Research progress of extracellular vesicles derived from mesenchymal stem cells in the treatment of neurodegenerative diseases.Frontiers in immunology · 2025Review
- Engineered exosomes: a promising drug delivery platform with therapeutic potential.Frontiers in molecular biosciences · 2025Review
- The impact of a heat therapy intervention on pain and fibromyalgia symptoms in patients with fibromyalgia: a pilot study.Frontiers in pain research (Lausanne, Switzerland) · 2025Article
- Exosomes: intriguing mediators of intercellular communication in the organism's response to noxious agents.Arhiv za higijenu rada i toksikologiju · 2024Review
- Neuronal CBP-1 is Required for Enhanced Body Muscle Proteostasis in Response to Reduced Translation Downstream of mTOR.Frontiers in bioscience (Landmark edition) · 2024Article
- Proteomic insights into extracellular vesicles in ALS for therapeutic potential of Ropinirole and biomarker discovery.Inflammation and regeneration · 2024Article
- Thermotolerance in S. cerevisiae as a model to study extracellular vesicle biology.Journal of extracellular vesicles · 2024Article
- Low-Density Lipoproteins Increase Proliferation, Invasion, and Chemoresistance via an Exosome Autocrine Mechanism in MDA-MB-231 Chemoresistant Cells.Biomedicines · 2024Article
- Immortalized Schwann cell lines as useful tools for pathogenesis-based therapeutic approaches to diabetic peripheral neuropathy.Frontiers in endocrinology · 2024Review
- Defining tropism and activity of natural and engineered extracellular vesicles.Frontiers in immunology · 2024Review
- B cell extracellular vesicles contain monomeric IgM that binds antigen and enters target cells.iScience · 2023Article
40 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The heat shock response (HSR), a transcriptional response that up-regulates molecular chaperones upon heat shock, is necessary for cell survival in a stressful environment to maintain protein homeostasis (proteostasis). However, there is accumulating evidence that the HSR does not ubiquitously occur under stress conditions, but largely depends on the cell types. Despite such imbalanced HSR among different cells and tissues, molecular mechanisms by which multicellular organisms maintain their global proteostasis have remained poorly understood. Here, we report that proteostasis can be maintained by molecular chaperones not only in a cell-autonomous manner but also in a non-cell-autonomous manner. We found that elevated expression of molecular chaperones, such as Hsp40 and Hsp70, in a group of cells improves proteostasis in other groups of cells, both in cultured cells and in Drosophila expressing aggregation-prone polyglutamine proteins. We also found that Hsp40, as well as Hsp70 and Hsp90, is physiologically secreted from cells via exosomes, and that the J domain at the N terminus is responsible for its exosome-mediated secretion. Addition of Hsp40/Hsp70-containing exosomes to the culture medium of the polyglutamine-expressing cells results in efficient suppression of inclusion body formation, indicating that molecular chaperones non-cell autonomously improve the protein-folding environment via exosome-mediated transmission. Our study reveals that intercellular chaperone transmission mediated by exosomes is a novel molecular mechanism for non-cell-autonomous maintenance of organismal proteostasis that could functionally compensate for the imbalanced state of the HSR among different cells, and also provides a novel physiological role of exosomes that contributes to maintenance of organismal proteostasis.
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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.