ArticleeLife2018
Gq activity- and β-arrestin-1 scaffolding-mediated ADGRG2/CFTR coupling are required for male fertility.
Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 51 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.
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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.
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Who cites it
51 citing papers in PubMed, 85 citations in OpenAlex.
- Review
- The therapeutic potential of orphan adhesion G-protein-coupled receptors.Nature reviews. Drug discovery · 2026Review
- Dehydroepiandrosterone activates ADGRG2 to regulate chloride homeostasis and sperm motility via Gs-cAMP pathways.Science China. Life sciences · 2026Article
- Therapeutic targeting of adhesion GPCRs: a status update and future potential.Expert opinion on drug discovery · 2026Review
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- Clinical subgroup-stratified plasma proteomic signatures improve risk prediction for myocardial infarction: SCORE2-Pro.Cardiovascular diabetology · 2026Article
- Article
- Development of an allosteric adhesion GPCR nanobody with therapeutic potential.Nature chemical biology · 2025Article
- The structural basis of the G protein-coupled receptor and ion channel axis.Current research in structural biology · 2025Review
- ARL13B controls male reproductive tract physiology through primary and Motile Cilia.Communications biology · 2024Article
- SperMD: the expression atlas of sperm maturation.BMC bioinformatics · 2024Article
- Mechanistic Insights into Peptide Binding and Deactivation of an Adhesion G Protein-Coupled Receptor.Molecules (Basel, Switzerland) · 2023Article
- Proteomic approach towards identification of seminal fluid biomarkers from individuals with severe oligozoospermia, cryptozoospermia and non-obstructive azoospermia: a pilot study.Translational andrology and urology · 2023Article
- Adhesion G protein-coupled receptor G2 is dispensable for lumicrine signaling regulating epididymal initial segment differentiation and gene expression†.Biology of reproduction · 2023Article
- GPR114/ADGRG5 is activated by its tethered peptide agonist because it is a cleaved adhesion GPCR.The Journal of biological chemistry · 2023Article
- A novel ADGRG2 truncating variant associated with X-linked obstructive azoospermia in a large Chinese pedigree.Journal of assisted reproduction and genetics · 2023Article
- Tissue-Specific Regulation ofInternational journal of molecular sciences · 2023Review
- Deafness-Associated ADGRV1 Mutation Impairs USH2A Stability through Improper Phosphorylation of WHRN and WDSUB1 Recruitment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Structure insights into selective coupling of G protein subtypes by a class B G protein-coupled receptor.Nature communications · 2022Article
- Adhesion G protein-coupled receptors: structure, signaling, physiology, and pathophysiology.Physiological reviews · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
28 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Luminal fluid reabsorption plays a fundamental role in male fertility. We demonstrated that the ubiquitous GPCR signaling proteins Gq and β-arrestin-1 are essential for fluid reabsorption because they mediate coupling between an orphan receptor ADGRG2 (GPR64) and the ion channel CFTR. A reduction in protein level or deficiency of ADGRG2, Gq or β-arrestin-1 in a mouse model led to an imbalance in pH homeostasis in the efferent ductules due to decreased constitutive CFTR currents. Efferent ductule dysfunction was rescued by the specific activation of another GPCR, AGTR2. Further mechanistic analysis revealed that β-arrestin-1 acts as a scaffold for ADGRG2/CFTR complex formation in apical membranes, whereas specific residues of ADGRG2 confer coupling specificity for different G protein subtypes, this specificity is critical for male fertility. Therefore, manipulation of the signaling components of the ADGRG2-Gq/β-arrestin-1/CFTR complex by small molecules may be an effective therapeutic strategy for male infertility.
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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.