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Regulating extracellular proteostasis capacity through the unfolded protein response
Joseph C Genereux, R Luke Wiseman. Prion, 2015
Topic: Disease mechanisms in lab and animal studies
The extracellular aggregation of proteins into proteotoxic oligomers and amyloid fibrils is implicated in the onset and pathology of numerous diseases referred to as amyloid diseases. All of the proteins that aggregate extracellularly in association with amyloid disease pathogenesis originate in the endoplasmic reticulum (ER) and are secreted through the secretory pathway. Disruptions in ER protein homeostasis or proteostasis (i.e., ER stress) can facilitate the aberrant secretion of misfolded protein conformations to the extracellular space and exacerbate pathologic protein aggregation into proteotoxic species. Activation of an ER stress-responsive signaling pathway, the Unfolded Protein Response (UPR), restores ER proteostasis through the transcriptional regulation of ER proteostasis pathways. In contrast, the functional role for the UPR in regulating extracellular proteostasis during ER stress is poorly defined. We recently identified ERdj3 as a UPR-regulated secreted chaperone that increases extracellular proteostasis capacity in response to ER stress, revealing a previously-unanticipated direct mechanism by which the UPR impacts extracellular proteostasis. Here, we discuss the functional implications of ERdj3 secretion on extracellular proteostasis maintenance and define the mechanisms by which ERdj3 secretion coordinates intra- and extracellular proteostasis environments during ER stress.
Key findings
- Disruptions in ER protein homeostasis or proteostasis (i.e., ER stress) can facilitate the aberrant secretion of misfolded protein conformations to the extracellular space and exacerbate pathologic protein aggregation into proteotoxic species.
- Activation of an ER stress-responsive signaling pathway, the Unfolded Protein Response (UPR), restores ER proteostasis through the transcriptional regulation of ER proteostasis pathways.
- In contrast, the functional role for the UPR in regulating extracellular proteostasis during ER stress is poorly defined.
- We recently identified ERdj3 as a UPR-regulated secreted chaperone that increases extracellular proteostasis capacity in response to ER stress, revealing a previously-unanticipated direct mechanism by which the UPR impacts extracellular proteostasis.
- Here, we discuss the functional implications of ERdj3 secretion on extracellular proteostasis maintenance and define the mechanisms by which ERdj3 secretion coordinates intra- and extracellular proteostasis environments during ER stress.
Study details
- Evidence strengthLow
How this study scored 38/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 21 of the 56 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Prion) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25946012) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 21 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 21 of the 56 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Genereux, J. C., & Wiseman, R. L. (2015). Regulating extracellular proteostasis capacity through the unfolded protein response. Prion. https://doi.org/10.1080/19336896.2015.1011887
Vancouver
Genereux JC, Wiseman RL. Regulating extracellular proteostasis capacity through the unfolded protein response. Prion. 2015. doi:10.1080/19336896.2015.1011887. PMID: 25946012.
BibTeX
@article{genereux2015-25946012,
author = {Genereux, Joseph C and Wiseman, R Luke},
title = {{Regulating extracellular proteostasis capacity through the unfolded protein response}},
journal = {Prion},
year = {2015},
doi = {10.1080/19336896.2015.1011887},
pmid = {25946012},
url = {https://doi.org/10.1080/19336896.2015.1011887}
}
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