Evidence map›Paper›PMID 26490116›Full record

ArticleMolecular biology of the cell2015

The α-arrestin ARRDC3 mediates ALIX ubiquitination and G protein-coupled receptor lysosomal sorting.

Michael R Dores, Huilan Lin, Neil J Grimsey, Francisco Mendez, JoAnn Trejo

Open access · greenAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
3.5field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 83 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. International journal of molecular sciences · 2024
    Article
  6. Article
  7. Review
  8. Article
  9. Article
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  11. Article
  12. Spatial Mechano-Signaling Regulation of GTPases through Non-Degradative Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. α-Arrestins and Their Functions: From Yeast to Human Health.International journal of molecular sciences · 2022
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Michael R DoresDepartment of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093.
Huilan LinDepartment of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093.
Neil J GrimseyDepartment of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093.
Francisco MendezDepartment of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093.
JoAnn TrejoDepartment of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093 joanntrejo@ucsd.edu.
University of California San Diego · US

Funding

UCSD/SDSU IRACDAK12GM068524 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TREJO, JOANN · 2003 to 2025
$24.4M
Mechanisms Regulating GPCR TraffickingR01GM090689 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TREJO, JOANN · 2010 to 2018
$2.9M
NIGMS NIH HHS K12 GM06852NIGMS NIH HHS K12 GM068524NIGMS NIH HHS R01 GM090689
6 · The paper itself

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.

Indexed as

ProteolysisArrestinsCalcium-Binding ProteinsCell Cycle ProteinsEndosomal Sorting Complexes Required for TransportHeLa CellsHumansLysosomesNedd4 Ubiquitin Protein LigasesProtein BindingReceptor, PAR-1Receptors, G-Protein-CoupledSignal TransductionUbiquitinUbiquitinationUbiquitin-Protein LigasesARRDC3 protein, humanArrestinsCalcium-Binding ProteinsCell Cycle ProteinsEndosomal Sorting Complexes Required for TransportNedd4 protein, humanNedd4 Ubiquitin Protein LigasesPDCD6IP protein, humanReceptor, PAR-1Receptors, G-Protein-CoupledUbiquitinUbiquitin-Protein LigasesWWP2 protein, human

Identifiers

PMID26490116
PMCPMC4678022
OpenAlexW2272989235

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

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.