STING is ESCRTed to degradation by microautophagy

Assil, Sonia; Paludan, Søren R

doi:10.1038/s41556-022-01084-7

Cited by 3 publications

(2 citation statements)

References 11 publications

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“…Meanwhile, perinuclear integration of ERQC domains with proteolytic organelles facilitates lysosomal clearance of ERQC components through Sec62‐mediated ERphagy, which we now show is reliant upon RNF26 and vimentin. Given that this type of ERphagy is mediated by the ESCRT machinery, and we and others have previously implicated RNF26 in other ESCRT‐dependent processes, namely the downregulation of EGFR (Cremer et al , 2021 ) and degradation of STING (Qin et al , 2014 ; Assil & Paludan, 2023 ; Kuchitsu et al , 2023 ), interplay between RNF26, vimentin, and ESCRT complexes could be interesting to pursue in future studies. For instance, K63‐linked ubiquitin conjugates have been detected on RNF26 (Fenech et al , 2020 ), and this linkage type is known to be preferred by the ESCRT‐0 members Hrs and STAM (Nathan et al , 2013 ).…”

Section: Discussionmentioning

confidence: 99%

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

Cremer,

Voortman,

Bos

et al. 2023

The EMBO Journal

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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.

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Section: Discussionmentioning

confidence: 99%

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

Cremer,

Voortman,

Bos

et al. 2023

The EMBO Journal

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“…The endolysosomal degradation of ubiquitinated STING in murine macrophages requires endosomal complexes required for the transport (ESCRT) pathway involved in microautophagy for its recognition [129][130][131][132]. ESCRT deficiency or inhibition is associated with an overactivated cGAS/STING signaling pathway.…”

Section: Cgas/sting Signaling Pathway In Cellular and Immune Homeosta...mentioning

confidence: 99%

cGLRs Join Their Cousins of Pattern Recognition Receptor Family to Regulate Immune Homeostasis

Kumar,

Stewart

2024

IJMS

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Pattern recognition receptors (PRRs) recognize danger signals such as PAMPs/MAMPs and DAMPs to initiate a protective immune response. TLRs, NLRs, CLRs, and RLRs are well-characterized PRRs of the host immune system. cGLRs have been recently identified as PRRs. In humans, the cGAS/STING signaling pathway is a part of cGLRs. cGAS recognizes cytosolic dsDNA as a PAMP or DAMP to initiate the STING-dependent immune response comprising type 1 IFN release, NF-κB activation, autophagy, and cellular senescence. The present article discusses the emergence of cGLRs as critical PRRs and how they regulate immune responses. We examined the role of cGAS/STING signaling, a well-studied cGLR system, in the activation of the immune system. The following sections discuss the role of cGAS/STING dysregulation in disease and how immune cross-talk with other PRRs maintains immune homeostasis. This understanding will lead to the design of better vaccines and immunotherapeutics for various diseases, including infections, autoimmunity, and cancers.

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