Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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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))
  • Received : 2021.01.30
  • Accepted : 2021.05.27
  • Published : 2021.07.31
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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

Acknowledgement

This work was supported by a grant (NRF-2019M3E5D4069882) from the National Research Foundation, Ministry of Science and ICT and Future Planning, and a grant from the KRIBB Initiative Program.

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