O'Brien, D orcid.org/0000-0003-4441-3870, Jones, L, Good, S orcid.org/0000-0002-2263-0690 et al. (6 more authors) (2018) A PQM-1-mediated response triggers transcellular chaperone signaling and regulates organismal proteostasis. Cell Reports, 23 (13). pp. 3905-3919. ISSN 2211-1247
Abstract
In metazoans, tissues experiencing proteotoxic stress induce “transcellular chaperone signaling” (TCS) that activates molecular chaperones, such as hsp-90, in distal tissues. How this form of inter-tissue communication is mediated to upregulate systemic chaperone expression and whether it can be utilized to protect against protein misfolding diseases remain open questions. Using C. elegans, we identified key components of a systemic stress signaling pathway that links the innate immune response with proteostasis maintenance. We show that mild perturbation of proteostasis in the neurons or the intestine activates TCS via the GATA zinc-finger transcription factor PQM-1. PQM-1 coordinates neuron-activated TCS via the innate immunity-associated transmembrane protein CLEC-41, whereas intestine-activated TCS depends on the aspartic protease ASP-12. Both TCS pathways can induce hsp-90 in muscle cells and facilitate amelioration of Aβ₃-₄₂-associated toxicity. This may have powerful implications for the treatment of diseases related to proteostasis dysfunction.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | proteostasis; C. elegans; transcellular chaperone signaling; stress response; HSP-90; PQM-1; CLEC-41; ASP-12 |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 31 May 2018 11:18 |
Last Modified: | 25 Jun 2023 21:22 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.celrep.2018.05.093 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:131506 |