ArticleThe Journal of biological chemistry2017
The GPRC6A receptor displays constitutive internalization and sorting to the slow recycling pathway.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 47 citations in OpenAlex.
- Article
- The Emerging Roles of Metabolite-Activated GPCRs in Teleost Physiology and Aquaculture Development.Metabolites · 2025Review
- Constitutive internalisation of EP2 differentially regulates G protein signalling.Journal of molecular endocrinology · 2024Article
- Mechanisms and molecular targets surrounding the potential therapeutic effects of psychedelics.Molecular psychiatry · 2023Review
- Ligand-Free Signaling of G-Protein-Coupled Receptors: Physiology, Pharmacology, and Genetics.Molecules (Basel, Switzerland) · 2023Review
- Specific Signal Transduction of Constitutively Activating (D576G) and Inactivating (R476H) Mutants of Agonist-Stimulated Luteinizing Hormone Receptor in Eel.International journal of molecular sciences · 2023Article
- Patterns of human and porcine gammaherpesvirus-encoded BILF1 receptor endocytosis.Cellular & molecular biology letters · 2023Article
- Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors.Science (New York, N.Y.) · 2023Article
- Exploring ITM2A as a new potential target for brain delivery.Fluids and barriers of the CNS · 2022Article
- Cell-Surface Loss of Constitutive Activating and Inactivating Mutants of Eel Luteinizing Hormone Receptors.Development & reproduction · 2021Article
- Constitutively Activating Mutants of Equine LH/CGR Constitutively Induce Signal Transduction and Inactivating Mutations Impair Biological Activity and Cell-Surface Receptor Loss In Vitro.International journal of molecular sciences · 2021Article
- Explaining Divergent Observations Regarding Osteocalcin/GPRC6A Endocrine Signaling.Endocrinology · 2021Review
- Interclass GPCR heteromerization affects localization and trafficking.Science signaling · 2020Article
- Constitutive Activation and Inactivation of Mutations Inducing Cell Surface Loss of Receptor and Impairing of Signal Transduction of Agonist-Stimulated Eel Follicle-Stimulating Hormone Receptor.International journal of molecular sciences · 2020Article
- Humanized GPRC6AScientific reports · 2020Article
- Arrestin-independent constitutive endocytosis of GPR125/ADGRA3.Annals of the New York Academy of Sciences · 2019Article
- Human GPRC6A Mediates Testosterone-Induced Mitogen-Activated Protein Kinases and mTORC1 Signaling in Prostate Cancer Cells.Molecular pharmacology · 2019Article
- Mechanisms of signalling and biased agonism in G protein-coupled receptors.Nature reviews. Molecular cell biology · 2018Review
- FFAR2-FFAR3 receptor heteromerization modulates short-chain fatty acid sensing.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The class C G protein-coupled receptor GPRC6A is a putative nutrient-sensing receptor and represents a possible new drug target in metabolic disorders. However, the specific physiological role of this receptor has yet to be identified, and the mechanisms regulating its activity and cell surface availability also remain enigmatic. In the present study, we investigated the trafficking properties of GPRC6A by use of both a classical antibody feeding internalization assay in which cells were visualized using confocal microscopy and a novel internalization assay that is based on real-time measurements of fluorescence resonance energy transfer. Both assays revealed that GPRC6A predominantly undergoes constitutive internalization, whereas the agonist-induced effects were imperceptible. Moreover, postendocytic sorting was investigated by assessing the co-localization of internalized GPRC6A with selected Rab protein markers. Internalized GPRC6A was mainly co-localized with the early endosome marker Rab5 and the long loop recycling endosome marker Rab11 and to a much lesser extent with the late endosome marker Rab7. This suggests that upon agonist-independent internalization, GPRC6A is recycled via the Rab11-positive slow recycling pathway, which may be responsible for ensuring a persistent pool of GPRC6A receptors at the cell surface despite chronic agonist exposure. Distinct trafficking pathways have been reported for several of the class C receptors, and our results thus substantiate that non-canonical trafficking mechanisms are a common feature for the nutrient-sensing class C family that ensure functional receptors in the cell membrane despite prolonged agonist exposure.
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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.