Barki, N. et al. (2023) Phosphorylation bar-coding of free fatty acid receptor 2 is generated in a tissue-specific manner. eLife, 12, RP91861. (doi: 10.7554/eLife.91861) (PMID:38085667) (PMCID:PMC10715726)
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Abstract
Free Fatty Acid receptor 2 (FFA2) 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 FFA2 and a Designer Receptor Exclusively Activated by Designer Drugs (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 FFA2 or the FFA2-DREADD. FFA2 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.
| Item Type: | Articles |
|---|---|
| Additional Information: | These studies were supported by the Biotechnology and Biosciences Research Council U.K., grants numbers BB/X001814/1 and BB/S000453/1 (to GM and ABT). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Milligan, Professor Graeme and Tobin, Andrew and Nilsen, Mrs Margaret and Bolognini, Dr Daniele and Dwomoh, Dr Louis and Dedeo, Dr Domonkos and Barki, Ms Natasja and Stoffels, Manon and Jenkins, Mrs Laura and Abdelmalik, Aisha M Hassan and Marsango, Dr Sara |
| Authors: | Barki, N., Jenkins, L., Marsango, S., Dedeo, D., Bolognini, D., Dwomoh, L., Abdelmalik, A. M., Nilsen, M., Stoffels, M., Nagel, F., Schulz, S., Tobin, A. B., and Milligan, G. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| Journal Name: | eLife |
| Publisher: | eLife Sciences Publications |
| ISSN: | 2050-084X |
| ISSN (Online): | 2050-084X |
| Published Online: | 23 October 2023 |
| Copyright Holders: | Copyright © 2023 Barki et al. |
| First Published: | First published in eLife 12: RP91861 |
| Publisher Policy: | Reproduced under a Creative Commons License |
| Data DOI: | 10.5525/gla.researchdata.1535 |
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