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

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.

Citation

Bi-Oh Park, Seong Heon Kim, Jong Hwan Kim, Seon-Young Kim, Byoung Chul Park, Sang-Bae Han, Sung Goo Park, Jeong-Hoon Kim, Sunhong Kim. The Short-Chain Fatty Acid Receptor GPR43 Modulates YAP/TAZ via RhoA. Molecules and cells. 2021 Jul 31;44(7):458-467

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PMID: 34112743

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