Constitutively active GPR43 is crucial for proper leukocyte differentiation

Abstract

The G protein-coupled receptors, GPR43 (free fatty acid receptor 2, FFA2) and GPR41 (free fatty acid receptor 3, FFA3), are activated by short-chain fatty acids produced under various conditions, including microbial fermentation of carbohydrates. Previous studies have implicated this receptor energy homeostasis and immune responses as well as in cell growth arrest and apoptosis. Here, we observed the expression of both receptors in human blood cells and a remarkable enhancement in leukemia cell lines (HL-60, U937, and THP-1 cells) during differentiation. A reporter assay revealed that GPR43 is coupled with Gα i and Gα 12/13 and is constitutively active without any stimuli. Specific blockers of GPR43, GLPG0974

Generation of Comprehensive GPCR-Transducer-Deficient Cell Lines to Dissect the Complexity of GPCR Signaling

“…has not been copyedited and formatted. (Furness et al, 2016;Gao et al, 2018;Okashah et al, 2019;Lukasheva et al, 2020;Avet et al, 2022;Kwon et al, 2022) ∆Gα i1/i2/i3 HEK293 Rockman Lab (Wang et al, 2017) ∆Gα i HEK293 Inoue Lab (Ono et al, 2023) (Avet et al, 2022;Miyasato et al, 2023) ∆Gα q/11 HEK293 Inoue Lab (Schrage et al, 2015) (Alvarez-Curto et al, 2016Doçi et al, 2017;Jørgensen et al, 2017;Sergeev et al, 2017;Gao et al, 2018;Gorvin et al, 2018;Namkung et al, 2018;O'Brien et al, 2018;Inoue et al, 2019;Malfacini et al, 2019;Pfeil et al, 2020;Patt et al, 2021;Toyomoto et al, 2021;Avet et al, 2022;Randolph et al, 2022) ∆Gα 12/13 HEK293 Inoue Lab (Devost et al, 2017;Inoue et al, 2019) (Sergeev et al, 2017;Gorvin et al, 2018;Namkung et al, 2018;Okashah et al, 2019;Pfeil et al, 2020;Toyomoto et al, 2021;Avet et al, 2022;Miyasato et al, 2023) has not been copyedited and formatted. ∆Gα q/11/12/13 HEK293 Inoue Lab (Devost et al, 2017) (Sergeev et al, 2017;…”