ArticleMolecular biology of the cell2015
The α-arrestin ARRDC3 mediates ALIX ubiquitination and G protein-coupled receptor lysosomal sorting.
Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 83 citations in OpenAlex.
- ARRDC3 promotes lysosome-mediated YAP degradation to inhibit enterovirus replication.Virologica Sinica · 2025Article
- Rest Induces a Distinct Transcriptional Program in the Nervous System of the ExercisedInternational journal of molecular sciences · 2025Article
- USP34 regulates endothelial PAR1 mRNA transcript expression and cellular signaling.Molecular biology of the cell · 2025Article
- Extracellular vesicles: cargo loading, degradation and secretory pathways, and their intersection with autophagy.Extracellular vesicles and circulating nucleic acids · 2025Review
- Article
- Optimization of the fluorogen-activating protein tag for quantitative protein trafficking and colocalization studies inMolecular biology of the cell · 2024Article
- Ubiquitin-driven G protein-coupled receptor inflammatory signaling at the endosome.American journal of physiology. Cell physiology · 2024Review
- ALIX and TSG101 are essential for cellular entry and replication of two porcine alphacoronaviruses.PLoS pathogens · 2024Article
- Genome-wide CRISPR screening identifies a role for ARRDC3 in TRP53-mediated responses.Cell death and differentiation · 2024Article
- Article
- Distinct beta-arrestin coupling and intracellular trafficking of metabotropic glutamate receptor homo- and heterodimers.Science advances · 2023Article
- Spatial Mechano-Signaling Regulation of GTPases through Non-Degradative Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Divergent regulation of α-arrestin ARRDC3 function by ubiquitination.Molecular biology of the cell · 2023Article
- Avidity-Based Method for the Efficient Generation of Monoubiquitinated Recombinant Proteins.Journal of the American Chemical Society · 2023Article
- Transcriptional targets of senataxin and E2 promoter binding factors are associated with neuro-degenerative pathways during increased autophagic flux.Scientific reports · 2022Article
- Common and species-specific molecular signatures, networks, and regulators of influenza virus infection in mice, ferrets, and humans.Science advances · 2022Article
- The α-Arrestin ARRDC3 Is an Emerging Multifunctional Adaptor Protein in Cancer.Antioxidants & redox signaling · 2022Review
- α-Arrestins and Their Functions: From Yeast to Human Health.International journal of molecular sciences · 2022Review
- Transcriptomic analysis of functional diversity of human umbilical cord blood hematopoietic stem/progenitor cells in erythroid differentiation.International journal of hematology · 2022Article
- TORC1 Signaling Controls the Stability and Function of α-Arrestins Aly1 and Aly2.Biomolecules · 2022Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The sorting of G protein-coupled receptors (GPCRs) to lysosomes is critical for proper signaling and cellular responses. We previously showed that the adaptor protein ALIX regulates lysosomal degradation of protease-activated receptor-1 (PAR1), a GPCR for thrombin, independent of ubiquitin-binding ESCRTs and receptor ubiquitination. However, the mechanisms that regulate ALIX function during PAR1 lysosomal sorting are not known. Here we show that the mammalian α-arrestin arrestin domain-containing protein-3 (ARRDC3) regulates ALIX function in GPCR sorting via ubiquitination. ARRDC3 colocalizes with ALIX and is required for PAR1 sorting at late endosomes and degradation. Depletion of ARRDC3 by small interfering RNA disrupts ALIX interaction with activated PAR1 and the CHMP4B ESCRT-III subunit, suggesting that ARRDC3 regulates ALIX activity. We found that ARRDC3 is required for ALIX ubiquitination induced by activation of PAR1. A screen of nine mammalian NEDD4-family E3 ubiquitin ligases revealed a critical role for WWP2. WWP2 interacts with ARRDC3 and not ALIX. Depletion of WWP2 inhibited ALIX ubiquitination and blocked ALIX interaction with activated PAR1 and CHMP4B. These findings demonstrate a new role for the α-arrestin ARRDC3 and the E3 ubiquitin ligase WWP2 in regulation of ALIX ubiquitination and lysosomal sorting of GPCRs.
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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.