ArticleThe EMBO journal2023
TOLLIP acts as a cargo adaptor to promote lysosomal degradation of aberrant ER membrane proteins.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
18 citing papers in PubMed, 20 citations in OpenAlex.
- Redox cycling of viral RNA polymerase controls picornavirus replication.Nature communications · 2026Article
- Cleavage of TOM1 by the SARS-CoV-2 main protease NSP5 prevents autophagic degradation of viral envelope.Journal of virology · 2026Article
- TOM1 family proteins: from cargo sorting to immune dysregulation and cancer.Cell communication and signaling : CCS · 2026Review
- Mitochondria-Derived Vesicles and Mitochondrial Extracellular Vesicles in Health and Cardiovascular Disease.Circulation research · 2026Review
- FAM134B isoform 2/RETREG1-2 defines a calnexin-TOLLIP-coupled ER-phagy pathway that restricts Ebola virus glycoprotein and is antagonized by VP40 through macro-autophagy.bioRxiv : the preprint server for biology · 2026Article
- OCIAD2 Stabilizes Integrin β1 Signaling Through SNX17-Mediated Endosomal Recycling to Lipid Rafts and Modulates Cisplatin Response in HNSCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TOLLIP targets GSDME-NT-carrying endocytic vesicles for autophagy to regulate pyroptosis and chemotherapy efficacy.Nature cell biology · 2026Article
- ER remodelling is a feature of ageing and depends on ER-phagy.Nature cell biology · 2026Article
- Article
- African swine fever virus MGF505-4R facilitates cGAS degradation through TOLLIP-mediated selective autophagy and inhibits the formation of ISGF3 to evade innate immunity.Veterinary research · 2025Article
- Mitochondria-derived vesicles: A promising and potential target for tumour therapy.Clinical and translational medicine · 2025Review
- µMap proximity labeling in living cells reveals stress granule disassembly mechanisms.Nature chemical biology · 2025Article
- Massive ER protein disposal by reticulophagy receptors and selective disposal by TOLLIP.Autophagy · 2024Article
- ER-phagy drives age-onset remodeling of endoplasmic reticulum structure-function and lifespan.bioRxiv : the preprint server for biology · 2024Article
- The role of galectins in the regulation of autophagy and inflammasome in host immunity.Seminars in immunopathology · 2024Review
- ER exit in physiology and disease.Frontiers in molecular biosciences · 2024Review
- TOLLIP acts as a cargo adaptor to promote lysosomal degradation of aberrant ER membrane proteins.The EMBO journal · 2023Article
- Membrane Contact Sites in Proteostasis and ER Stress Response.Contact (Thousand Oaks (Ventura County, Calif.))Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Endoplasmic reticulum (ER) proteostasis is maintained by various catabolic pathways. Lysosomes clear entire ER portions by ER-phagy, while proteasomes selectively clear misfolded or surplus aberrant proteins by ER-associated degradation (ERAD). Recently, lysosomes have also been implicated in the selective clearance of aberrant ER proteins, but the molecular basis remains unclear. Here, we show that the phosphatidylinositol-3-phosphate (PI3P)-binding protein TOLLIP promotes selective lysosomal degradation of aberrant membrane proteins, including an artificial substrate and motoneuron disease-causing mutants of VAPB and Seipin. These cargos are recognized by TOLLIP through its misfolding-sensing intrinsically disordered region (IDR) and ubiquitin-binding CUE domain. In contrast to ER-phagy receptors, which clear both native and aberrant proteins by ER-phagy, TOLLIP selectively clears aberrant cargos by coupling them with the PI3P-dependent lysosomal trafficking without promoting bulk ER turnover. Moreover, TOLLIP depletion augments ER stress after ERAD inhibition, indicating that TOLLIP and ERAD cooperatively safeguard ER proteostasis. Our study identifies TOLLIP as a unique type of cargo-specific adaptor dedicated to the clearance of aberrant ER cargos and provides insights into molecular mechanisms underlying lysosome-mediated quality control of membrane proteins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.