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The Short-Chain Fatty Acid Receptor GPR43 Modulates YAP/TAZ via RhoA.
- Source :
- Molecules & Cells (Elsevier B.V); Jul2021, Vol. 44 Issue 7, p458-467, 10p
- Publication Year :
- 2021
-
Abstract
- GPR43 (also known as FFAR2 or FFA2) is a G-protein-coupled receptor primarily expressed in immune cells, enteroendocrine cells and adipocytes that recognizes short-chain fatty acids, such as acetate, propionate, and butyrate, likely to be implicated in innate immunity and host energy homeostasis. Activated GPR43 suppresses the cAMP level and induces Ca2+ flux via coupling to Gαi and Gαq families, respectively. Additionally, GPR43 is reported to facilitate phosphorylation of ERK through G-protein-dependent pathways and interacts with β-arrestin 2 to inhibit NF-κB signaling. However, other G-protein-dependent and independent signaling pathways involving GPR43 remain to be established. Here, we have demonstrated that GPR43 augments Rho GTPase signaling. Acetate and a synthetic agonist effectively activated RhoA and stabilized YAP/TAZ transcriptional coactivators through interactions of GPR43 with Gαq/11 and Gα12/13. Acetateinduced nuclear accumulation of YAP was blocked by a GPR43-specific inverse agonist. The target genes induced by YAP/TAZ were further regulated by GPR43. Moreover, in THP-1-derived M1-like macrophage cells, the Rho-YAP/TAZ pathway was activated by acetate and a synthetic agonist. Our collective findings suggest that GPR43 acts as a mediator of the Rho-YAP/TAZ pathway. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10168478
- Volume :
- 44
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Molecules & Cells (Elsevier B.V)
- Publication Type :
- Academic Journal
- Accession number :
- 151730449
- Full Text :
- https://doi.org/10.14348/molcells.2021.0021