RNF26 binds perinuclear vimentin filaments to integrate ER and endolysosomal responses to proteotoxic stress.

Autor: Cremer T; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.; Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands., Voortman LM; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands., Bos E; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands., Jongsma ML; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.; Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands., Ter Haar LR; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands., Akkermans JJ; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.; Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands., Talavera Ormeño CM; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands., Wijdeven RH; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.; Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands.; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam University Medical Center, Amsterdam, The Netherlands., de Vries J; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands., Kim RQ; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands., Janssen GM; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands., van Veelen PA; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands., Koning RI; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands., Neefjes J; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.; Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands., Berlin I; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.; Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2023 Sep 18; Vol. 42 (18), pp. e111252. Date of Electronic Publication: 2023 Jul 31.
DOI: 10.15252/embj.2022111252
Abstrakt: 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.
(© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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