ArticleBMC research notes2014
The extracellular N-terminal domain of G-protein coupled receptor 83 regulates signaling properties and is an intramolecular inverse agonist.
Article in BMC research notes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 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
5 citing papers in PubMed, 16 citations in OpenAlex.
- Neuropeptide PEN and Its Receptor GPR83: Distribution, Signaling, and Regulation.ACS chemical neuroscience · 2019Review
- Orphan neuropeptides and receptors: Novel therapeutic targets.Pharmacology & therapeutics · 2018Review
- Prediction and validation of the structural features of Ov58GPCR, an immunogenic determinant of Onchocerca volvulus.PloS one · 2018Article
- Identification of GPR83 as the receptor for the neuroendocrine peptide PEN.Science signaling · 2016Article
- Insights into Basal Signaling Regulation, Oligomerization, and Structural Organization of the Human G-Protein Coupled Receptor 83.PloS one · 2016Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRecently, the orphan G-protein coupled receptor 83 (GPR83) was identified as a new participant in body weight regulation. This receptor is highly expressed in the hypothalamic arcuate nucleus and is regulated in response to nutrient availability. Gpr83 knock-out mice are protected from diet-induced obesity. Moreover, in a previous study, we designed and characterized several artificial constitutively activating mutations (CAMs) in GPR83. A particular CAM was located in the extracellular N-terminal domain (eNDo) that is highly conserved among GPR83 orthologs. This suggests the contribution of this receptor part into regulation of signaling, which needed a more detailed investigation.
findingsIn this present study, therefore, we further explored the role of the eNDo in regulating GPR83-signaling and demonstrate a proof-of-principle approach in that deletion mutants are characterized by a strong increase in basal Gq/11-mediated signaling, whilst none of the additionally characterized signaling pathways (Gs, Gi, G12/13) were activated by the N-terminal deletion variants. Of note, we detected basal GPR83 MAPK-activity of the wild type receptor, which was not increased in the deletion variants.
conclusionsFinally, the extracellular portion of GPR83 has a strong regulatory function on this receptor. A suppressive - inverse agonistic - effect of the eNDo on GPR83 signaling activity is demonstrated here, which also suggests a putative link between extracellular receptor activation and proteolytic cleavage. These new insights highlight important aspects of GPR83-regulation and might open options in the development of tools to modulate GPR83-signaling.
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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.