Natural biased signaling of hydroxycarboxylic acid receptor 3 and G protein-coupled receptor 84.


Journal

Cell communication and signaling : CCS
ISSN: 1478-811X
Titre abrégé: Cell Commun Signal
Pays: England
ID NLM: 101170464

Informations de publication

Date de publication:
26 02 2020
Historique:
received: 15 10 2019
accepted: 29 01 2020
entrez: 28 2 2020
pubmed: 28 2 2020
medline: 9 7 2021
Statut: epublish

Résumé

Medium-chain fatty acids and their 3-hydroxy derivatives are metabolites endogenously produced in humans, food-derived or originating from bacteria. They activate G protein-coupled receptors, including GPR84 and HCA To study the signaling kinetics and components involved in signal transduction of both receptors we applied the label-free dynamic mass redistribution technology in combination with classical cAMP, ERK signaling and β-arrestin-2 recruitment assays. For phenotypical analyses, we used spheroid cell culture models. We present strong evidence for a natural biased signaling of structurally highly similar agonists at HCA In summary, our results highlight that biased agonism is a physiological property of HCA

Sections du résumé

BACKGROUND
Medium-chain fatty acids and their 3-hydroxy derivatives are metabolites endogenously produced in humans, food-derived or originating from bacteria. They activate G protein-coupled receptors, including GPR84 and HCA
METHODS
To study the signaling kinetics and components involved in signal transduction of both receptors we applied the label-free dynamic mass redistribution technology in combination with classical cAMP, ERK signaling and β-arrestin-2 recruitment assays. For phenotypical analyses, we used spheroid cell culture models.
RESULTS
We present strong evidence for a natural biased signaling of structurally highly similar agonists at HCA
CONCLUSIONS
In summary, our results highlight that biased agonism is a physiological property of HCA

Identifiants

pubmed: 32102673
doi: 10.1186/s12964-020-0516-2
pii: 10.1186/s12964-020-0516-2
pmc: PMC7045412
doi:

Substances chimiques

GPR84 protein, human 0
HCAR3 protein, human 0
Receptors, G-Protein-Coupled 0
Receptors, Nicotinic 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Video-Audio Media

Langues

eng

Sous-ensembles de citation

IM

Pagination

31

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Auteurs

Anna Peters (A)

Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, Leipzig University, Johannisallee 30, 04103, Leipzig, Germany.

Philipp Rabe (P)

Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, Leipzig University, Johannisallee 30, 04103, Leipzig, Germany.

Petra Krumbholz (P)

Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, Leipzig University, Johannisallee 30, 04103, Leipzig, Germany.

Hermann Kalwa (H)

Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, Leipzig University, Härtelstraße 16-18, 04107, Leipzig, Germany.

Robert Kraft (R)

Carl Ludwig Institute for Physiology, Medical Faculty, Leipzig University, 04103, Leipzig, Germany.

Torsten Schöneberg (T)

Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, Leipzig University, Johannisallee 30, 04103, Leipzig, Germany.

Claudia Stäubert (C)

Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, Leipzig University, Johannisallee 30, 04103, Leipzig, Germany. claudia.staeubert@medizin.uni-leipzig.de.

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Classifications MeSH