ArticlePloS one2013
Gpr3 stimulates Aβ production via interactions with APP and β-arrestin2.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- GPR3 in neuro-metabolic-immune-reproductive nexus - a potential therapeutic target for Multi-System diseases.Annals of medicine · 2026Pooled it
- Discovery of Small Molecule Ligands Targeting Orphan G Protein-Coupled Receptors GPR3, GPR6, and GPR12.Journal of medicinal chemistry · 2026Review
- Divergent Roles of mGlu2 and mGlu3 Receptors in Amyloid-β Production and Cognitive Dysfunctions in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mechanism and function of GPR3 regulated by a negative allosteric modulator.Nature communications · 2025Article
- The multifaceted functions of β-arrestins and their therapeutic potential in neurodegenerative diseases.Experimental & molecular medicine · 2024Review
- Activation of GPR3-β-arrestin2-PKM2 pathway in Kupffer cells stimulates glycolysis and inhibits obesity and liver pathogenesis.Nature communications · 2024Article
- Investigation of Potential Drug Targets Involved in Inflammation Contributing to Alzheimer's Disease Progression.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Development of Fluorescent AF64394 Analogues Enables Real-Time Binding Studies for the Orphan Class A GPCR GPR3.Journal of medicinal chemistry · 2023Article
- The development of diphenyleneiodonium analogs as GPR3 agonists.Bioorganic & medicinal chemistry letters · 2023Article
- The role of opioid receptors in modulating Alzheimer's Disease.Frontiers in pharmacology · 2023Review
- Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer's Disease.Biomedicines · 2022Article
- Review
- GPR3, GPR6, and GPR12 as novel molecular targets: their biological functions and interaction with cannabidiol.Acta pharmacologica Sinica · 2019Review
- Allosteric sodium binding cavity in GPR3: a novel player in modulation of Aβ production.Scientific reports · 2018Article
- Importance of GPCR-Mediated Microglial Activation in Alzheimer's Disease.Frontiers in cellular neuroscience · 2018Review
- The amyloid precursor protein modulates αFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Arrestins contribute to amyloid beta-induced cell death via modulation of autophagy and the α7nAch receptor in SH-SY5Y cells.Scientific reports · 2017Article
- An Update on Non-CBCannabis and cannabinoid research · 2017Review
- Methods for the Development of In Silico GPCR Models.Methods in enzymology · 2017Article
- Identifying ligands at orphan GPCRs: current status using structure-based approaches.British journal of pharmacology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The orphan G protein-coupled receptor (GPCR) GPR3 enhances the processing of Amyloid Precursor Protein (APP) to the neurotoxic beta-amyloid (Aβ) peptide via incompletely understood mechanisms. Through overexpression and shRNA knockdown experiments in HEK293 cells, we show that β-arrestin2 (βarr2), a GPCR-interacting scaffold protein reported to bind γ-secretase, is an essential factor for GPR3-stimulated Aβ production. For a panel of GPR3 receptor mutants, the degree of stimulation of Aβ production correlates with receptor-β-arrestin binding and receptor trafficking to endocytic vesicles. However, GPR3's recruitment of βarr2 cannot be the sole explanation, because interaction with βarr2 is common to most GPCRs, whereas GPR3 is relatively unique among GPCRs in enhancing Aβ production. In addition to β-arrestin, APP is present in a complex with GPR3 and stimulation of Aβ production by GPR3 mutants correlates with their level of APP binding. Importantly, among a broader selection of GPCRs, only GPR3 and prostaglandin E receptor 2 subtype EP2 (PTGER2; another GPCR that increases Aβ production) interact with APP, and PTGER2 does so in an agonist-stimulated manner. These data indicate that a subset of GPCRs, including GPR3 and PTGER2, can associate with APP when internalized via βarr2, and thereby promote the cleavage of APP to generate Aβ.
Indexed as
Identifiers
What OpenQuestion holds
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.