ArticleThe Journal of biological chemistry2014
Constitutive Gαi coupling activity of very large G protein-coupled receptor 1 (VLGR1) and its regulation by PDZD7 protein.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 75 citations in OpenAlex.
- The therapeutic potential of orphan adhesion G-protein-coupled receptors.Nature reviews. Drug discovery · 2026Review
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- Characterization of Usher Syndrome Type 2-Associated Proteins in the Retina via Affinity Purification-Mass Spectrometry.Molecular & cellular proteomics : MCP · 2026Article
- Super-resolution mapping of the ankle link proteins ADGRV1 and PDZD7 in developing auditory hair cells.iScience · 2025Article
- Mechanosensitive adhesion G protein-coupled receptors: Insights from health and disease.Genes & diseases · 2025Review
- Complex G-protein signaling of the adhesion GPCR, ADGRA3.The Journal of biological chemistry · 2025Article
- The BBS/CCT chaperonin complex ensures the localization of the adhesion G protein-coupled receptor ADGRV1 to the base of primary cilia.Frontiers in cell and developmental biology · 2025Article
- Novel GPR156 variants confirm its role in moderate sensorineural hearing loss.Scientific reports · 2023Article
- Deafness-Associated ADGRV1 Mutation Impairs USH2A Stability through Improper Phosphorylation of WHRN and WDSUB1 Recruitment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Adenylyl cyclase 6 plays a minor role in the mouse inner ear and retina.Scientific reports · 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
- Identification a novel de novo RUNX2 frameshift mutation associated with cleidocranial dysplasia.Genes & genomics · 2022Article
- Affinity Proteomics Identifies Interaction Partners and Defines Novel Insights into the Function of the Adhesion GPCR VLGR1/ADGRV1.Molecules (Basel, Switzerland) · 2022Article
- Progesterone activates GPR126 to promote breast cancer development via the Gi pathway.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Deciphering the Molecular Interaction Between the Adhesion G Protein-Coupled Receptor ADGRV1 and its PDZ-Containing Regulator PDZD7.Frontiers in molecular biosciences · 2022Article
- Activation pathway of a G protein-coupled receptor uncovers conformational intermediates as targets for allosteric drug design.Nature communications · 2021Article
- Cartilage oligomeric matrix protein is an endogenous β-arrestin-2-selective allosteric modulator of AT1 receptor counteracting vascular injury.Cell research · 2021Article
- Adhesion G protein-coupled receptor VLGR1/ADGRV1 regulates cell spreading and migration by mechanosensing at focal adhesions.iScience · 2021Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The very large G protein-coupled receptor 1 (VLGR1) is a core component in inner ear hair cell development. Mutations in the vlgr1 gene cause Usher syndrome, the symptoms of which include congenital hearing loss and progressive retinitis pigmentosa. However, the mechanism of VLGR1-regulated intracellular signaling and its role in Usher syndrome remain elusive. Here, we show that VLGR1 is processed into two fragments after autocleavage at the G protein-coupled receptor proteolytic site. The cleaved VLGR1 β-subunit constitutively inhibited adenylate cyclase (AC) activity through Gαi coupling. Co-expression of the Gαiq chimera with the VLGR1 β-subunit changed its activity to the phospholipase C/nuclear factor of activated T cells signaling pathway, which demonstrates the Gαi protein coupling specificity of this subunit. An R6002A mutation in intracellular loop 2 of VLGR1 abolished Gαi coupling, but the pathogenic VLGR1 Y6236fsx1 mutant showed increased AC inhibition. Furthermore, overexpression of another Usher syndrome protein, PDZD7, decreased the AC inhibition of the VLGR1 β-subunit but showed no effect on the VLGR1 Y6236fsx1 mutant. Taken together, we identified an independent Gαi signaling pathway of the VLGR1 β-subunit and its regulatory mechanisms that may have a role in the development of Usher syndrome.
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