ArticleThe Journal of cell biology2012
ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting.
Article in The Journal of cell biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.
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Who cites it
116 citing papers in PubMed, 157 citations in OpenAlex.
- Endosomes as central hubs of interorganellar communication and cellular homeostasis.Protein & cell · 2026Review
- Signaling bias of the protease-activated receptor-1 is dictated by distinct GRK5 and β-arrestin-2 determinants.Cell reports · 2026Article
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- Extracellular vesicles: biogenesis mechanism and impacts on tumor immune microenvironment.Journal of biomedical science · 2025Review
- The hepatocyte traffic network in the human hepatitis A virus biological cycle from an evolutionary perspective.Communications biology · 2025Article
- USP34 regulates endothelial PAR1 mRNA transcript expression and cellular signaling.Molecular biology of the cell · 2025Article
- Endosomal traffic disorders: a driving force behind neurodegenerative diseases.Translational neurodegeneration · 2024Review
- The Rubicon-WIPI axis regulates exosome biogenesis during ageing.Nature cell biology · 2024Article
- The Conserved YPXViruses · 2024Article
- Ubiquitin-driven G protein-coupled receptor inflammatory signaling at the endosome.American journal of physiology. Cell physiology · 2024Review
- Exosomes: Methods for Isolation and Characterization in Biological Samples.Methods in molecular biology (Clifton, N.J.) · 2024Review
- Research progress on the mechanism of exosome-mediated virus infection.Frontiers in cellular and infection microbiology · 2024Review
- Cargo exchange between human and bacterial extracellular vesicles in gestational tissues: a new paradigm in communication and immune development.Extracellular vesicles and circulating nucleic acids · 2024Review
- Divergent regulation of α-arrestin ARRDC3 function by ubiquitination.Molecular biology of the cell · 2023Article
- Context-specific regulation of extracellular vesicle biogenesis and cargo selection.Nature reviews. Molecular cell biology · 2023Review
- The Roles of Exosomal Proteins: Classification, Function, and Applications.International journal of molecular sciences · 2023Review
- Biogenesis of extracellular vesicles in protozoan parasites: The ESCRT complex in the trafficking fast lane?PLoS pathogens · 2023Review
- Exosomal transmission of viruses, a two-edged biological sword.Cell communication and signaling : CCS · 2023Review
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
56 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The sorting of signaling receptors to lysosomes is an essential regulatory process in mammalian cells. During degradation, receptors are modified with ubiquitin and sorted by endosomal sorting complex required for transport (ESCRT)-0, -I, -II, and -III complexes into intraluminal vesicles (ILVs) of multivesicular bodies (MVBs). However, it remains unclear whether a single universal mechanism mediates MVB sorting of all receptors. We previously showed that protease-activated receptor 1 (PAR1), a G protein-coupled receptor (GPCR) for thrombin, is internalized after activation and sorted to lysosomes independent of ubiquitination and the ubiquitin-binding ESCRT components hepatocyte growth factor-regulated tyrosine kinase substrate and Tsg101. In this paper, we report that PAR1 sorted to ILVs of MVBs through an ESCRT-III-dependent pathway independent of ubiquitination. We further demonstrate that ALIX, a charged MVB protein 4-ESCRT-III interacting protein, bound to a YPX(3)L motif of PAR1 via its central V domain to mediate lysosomal degradation. This study reveals a novel MVB/lysosomal sorting pathway for signaling receptors that bypasses the requirement for ubiquitination and ubiquitin-binding ESCRTs and may be applicable to a subset of GPCRs containing YPX(n)L motifs.
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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.