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http://dx.doi.org/10.14348/molcells.2021.0021

The Short-Chain Fatty Acid Receptor GPR43 Modulates YAP/TAZ via RhoA  

Park, Bi-Oh (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Kim, Seong Heon (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Kim, Jong Hwan (Personalized Genomic Medicine Research Center, KRIBB)
Kim, Seon-Young (Personalized Genomic Medicine Research Center, KRIBB)
Park, Byoung Chul (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Han, Sang-Bae (College of Pharmacy, Chungbuk National University)
Park, Sung Goo (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Kim, Jeong-Hoon (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Kim, Sunhong (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Publication Information
Molecules and Cells / v.44, no.7, 2021 , pp. 458-467 More about this Journal
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. Acetate-induced 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.
Keywords
GPR43; RhoA; short-chain fatty acid; TAZ; YAP;
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