RNF26 binds perinuclear vimentin filaments to integrate ER and endolysosomal responses to proteotoxic stress
Open accessPublished version of a preprint
Abstract
Proteotoxic stress causes profound endoplasmic reticulum (ER) membrane remodeling into a perinuclear quality control compartment (ERQC) for the degradation of misfolded proteins. Subsequent return to homeostasis involves clearance of the ERQC by endolysosomes. However, the factors that control perinuclear ER integrity and dynamics remain unclear. Here, we identify vimentin intermediate filaments as perinuclear anchors for the ER and endolysosomes. We show that perinuclear vimentin filaments engage the ER‐embedded RING finger protein 26 (RNF26) at the C‐terminus of its RING domain. This restricts RNF26 to perinuclear ER subdomains and enables the corresponding spatial retention of endolysosomes through RNF26‐mediated membrane contact sites (MCS). We find that both RNF26 and vimentin are required for the perinuclear coalescence of the ERQC and its juxtaposition with proteolytic compartments, which facilitates efficient recovery from ER stress via the Sec62‐mediated ER‐phagy pathway. Collectively, our findings reveal a scaffolding mechanism that underpins the spatiotemporal integration of organelles during cellular proteostasis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Kinesin superfamily motor proteins and intracellular transport
Hirokawa, N., Noda, Y., Tanaka, Y., & Niwa, S. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2774 · Cited by 1,859 · cited 1× · see citing works
“While the roles of microtubule and actin networks with respect to organellar organization and motility have been extensively studied (Hirokawa et al , 2009; Reck-Peterson et al , 2018; Svit-kina, 2018), contributions of intermediate filaments (IFs) in this context are only beginning to emerge…”
Endoplasmic reticulum stress and unfolded protein response in cardiovascular diseases
Ren, J., Bi, Y., Sowers, J. R., Hetz, C., & Zhang, Y. (2021) · Nature Reviews Cardiology · doi:10.1038/s41569-021-00511-w · Cited by 708 · cited 1× · see citing works
“As the organelle responsible for production of all membrane and secretory proteins, the ER regularly experiences proteotoxic stress, which is implicated in various human pathologies (Hetz & Saxena, 2017; Ren et al , 2021; Ajoolabady et al , 2023).”
The position of lysosomes within the cell determines their luminal pH
Johnson, D. E., Ostrowski, P., Jaumouillé, V., & Grinstein, S. (2016) · Journal of Cell Biology · doi:10.1083/jcb.201507112 · Cited by 590 · see citing works
Flagged first, then by citations
- Authors
- Cremer, T., Voortman, L. M., Bos, E., Jongsma, M. L., ter Haar, L. R., Akkermans, J. J., Talavera Ormeño, C. M., Wijdeven, R. H., de Vries, J., Kim, R. Q., Janssen, G. M., van Veelen, P. A., Koning, R. I., Neefjes, J., & Berlin, I.
- Affiliations
- Leiden University Medical Center (NL)
- Corresponding author
- Neefjes, Jacques
- Berlin, Ilana
- ORCID
- Venue
- The EMBO Journal
- Published
- 2023-07-31
- Volume
- 42
- Issue
- 18
- Pages
- e111252-e111252
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC10505911
- OpenAlex
- W4385407025
- Cited by
- 35
- References
- 4
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 6 · 2023: 6 · 2022: 1
- FWCI
- 4.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- The EMBO Journal (publishedVersion, other-oa)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion, cc-by)
- VU Research Portal (submittedVersion)
- Funders
- EC ¦ European Research Council (694307)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- vimentin intermediate filaments, endoplasmic reticulum quality control, endoplasmic reticulum stress, proteotoxic stress, endolysosomes, membrane contact sites, ER-phagy, Sec62, RING domain, proteostasis, protein degradation
- MeSH terms
- Proteotoxic Stress, Autophagy, Endoplasmic Reticulum, Intermediate Filaments, Vimentin, Endoplasmic Reticulum Stress
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
