Article (Scientific journals)
Phosphorylation bar-coding of free fatty acid receptor 2 is generated in a tissue-specific manner.
Barki, Natasja; Jenkins, Laura; Marsango, Sara et al.
2023In eLife, 12
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Keywords :
G protein-coupled receptor; biochemistry; chemical biology; free fatty acid; mouse; phosphorylation; Fatty Acids, Nonesterified; Fatty Acids, Volatile; Receptors, G-Protein-Coupled; FFA2R protein, human; Animals; Humans; Mice; Cell Line; Fatty Acids, Volatile/metabolism; Mice, Transgenic; Phosphorylation; Receptors, G-Protein-Coupled/metabolism; Neuroscience (all); Biochemistry, Genetics and Molecular Biology (all); Immunology and Microbiology (all); General Immunology and Microbiology; General Biochemistry, Genetics and Molecular Biology; General Medicine; General Neuroscience
Abstract :
[en] Free fatty acid receptor 2 (FFAR2) is activated by short-chain fatty acids and expressed widely, including in white adipocytes and various immune and enteroendocrine cells. Using both wild-type human FFAR2 and a designer receptor exclusively activated by designer drug (DREADD) variant we explored the activation and phosphorylation profile of the receptor, both in heterologous cell lines and in tissues from transgenic knock-in mouse lines expressing either human FFAR2 or the FFAR2-DREADD. FFAR2 phospho-site-specific antisera targeting either pSer296/pSer297 or pThr306/pThr310 provided sensitive biomarkers of both constitutive and agonist-mediated phosphorylation as well as an effective means to visualise agonist-activated receptors in situ. In white adipose tissue, phosphorylation of residues Ser296/Ser297 was enhanced upon agonist activation whilst Thr306/Thr310 did not become phosphorylated. By contrast, in immune cells from Peyer's patches Thr306/Thr310 become phosphorylated in a strictly agonist-dependent fashion whilst in enteroendocrine cells of the colon both Ser296/Ser297 and Thr306/Thr310 were poorly phosphorylated. The concept of phosphorylation bar-coding has centred to date on the potential for different agonists to promote distinct receptor phosphorylation patterns. Here, we demonstrate that this occurs for the same agonist-receptor pairing in different patho-physiologically relevant target tissues. This may underpin why a single G protein-coupled receptor can generate different functional outcomes in a tissue-specific manner.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Barki, Natasja ;  Centre for Translational Pharmacology, School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
Jenkins, Laura;  Centre for Translational Pharmacology, School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
Marsango, Sara;  Centre for Translational Pharmacology, School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
Dedeo, Domonkos ;  Centre for Translational Pharmacology, School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
Bolognini, Daniele;  Centre for Translational Pharmacology, School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
Dwomoh, Louis ;  Centre for Translational Pharmacology, School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
Abdelmalik, Aisha M;  Centre for Translational Pharmacology, School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
Nilsen, Margaret;  Centre for Translational Pharmacology, School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
Stoffels, Manon  ;  Université de Liège - ULiège > GIGA > GIGA Molecular Biology of Diseases - Molecular Pharmacology ; Centre for Translational Pharmacology, School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
Nagel, Falko;  7TM Antibodies GmbH, Jena, Germany
Schulz, Stefan;  7TM Antibodies GmbH, Jena, Germany ; Institute of Pharmacology and Toxicology, University Hospital Jena, Jena, Germany
Tobin, Andrew B ;  Centre for Translational Pharmacology, School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
Milligan, Graeme ;  Centre for Translational Pharmacology, School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
More authors (3 more) Less
Language :
English
Title :
Phosphorylation bar-coding of free fatty acid receptor 2 is generated in a tissue-specific manner.
Publication date :
12 December 2023
Journal title :
eLife
eISSN :
2050-084X
Publisher :
eLife Sciences Publications Ltd, England
Volume :
12
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
BBSRC - Biotechnology and Biological Sciences Research Council [GB]
Funding text :
These studies were supported by the Biotechnology and Biosciences Research Council UK, grants numbers BB/X001814/1 and BB/S000453/1 (to GM and ABT).
Available on ORBi :
since 25 January 2024

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