Extracellular succinate hyperpolarizes M2 macrophages through SUCNR1/GPR91-mediated Gq signaling

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Extracellular succinate hyperpolarizes M2 macrophages through SUCNR1/GPR91-mediated Gq signaling. / Trauelsen, Mette; Hiron, Thomas K.; Lin, Da; Petersen, Jacob E.; Breton, Billy; Husted, Anna Sofie; Hjorth, Siv A.; Inoue, Asuka; Frimurer, Thomas M.; Bouvier, Michel; O'Callaghan, Chris A.; Schwartz, Thue W.

In: Cell Reports, Vol. 35, No. 11, 109246, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Trauelsen, M, Hiron, TK, Lin, D, Petersen, JE, Breton, B, Husted, AS, Hjorth, SA, Inoue, A, Frimurer, TM, Bouvier, M, O'Callaghan, CA & Schwartz, TW 2021, 'Extracellular succinate hyperpolarizes M2 macrophages through SUCNR1/GPR91-mediated Gq signaling', Cell Reports, vol. 35, no. 11, 109246. https://doi.org/10.1016/j.celrep.2021.109246

APA

Trauelsen, M., Hiron, T. K., Lin, D., Petersen, J. E., Breton, B., Husted, A. S., Hjorth, S. A., Inoue, A., Frimurer, T. M., Bouvier, M., O'Callaghan, C. A., & Schwartz, T. W. (2021). Extracellular succinate hyperpolarizes M2 macrophages through SUCNR1/GPR91-mediated Gq signaling. Cell Reports, 35(11), [109246]. https://doi.org/10.1016/j.celrep.2021.109246

Vancouver

Trauelsen M, Hiron TK, Lin D, Petersen JE, Breton B, Husted AS et al. Extracellular succinate hyperpolarizes M2 macrophages through SUCNR1/GPR91-mediated Gq signaling. Cell Reports. 2021;35(11). 109246. https://doi.org/10.1016/j.celrep.2021.109246

Author

Trauelsen, Mette ; Hiron, Thomas K. ; Lin, Da ; Petersen, Jacob E. ; Breton, Billy ; Husted, Anna Sofie ; Hjorth, Siv A. ; Inoue, Asuka ; Frimurer, Thomas M. ; Bouvier, Michel ; O'Callaghan, Chris A. ; Schwartz, Thue W. / Extracellular succinate hyperpolarizes M2 macrophages through SUCNR1/GPR91-mediated Gq signaling. In: Cell Reports. 2021 ; Vol. 35, No. 11.

Bibtex

@article{71ee10ffe5ea4f05b785d51d1f51e25f,
title = "Extracellular succinate hyperpolarizes M2 macrophages through SUCNR1/GPR91-mediated Gq signaling",
abstract = "Succinate functions both as a classical TCA cycle metabolite and an extracellular metabolic stress signal sensed by the mainly Gi-coupled succinate receptor SUCNR1. In the present study, we characterize and compare effects and signaling pathways activated by succinate and both classes of non-metabolite SUCNR1 agonists. By use of specific receptor and pathway inhibitors, rescue in G-protein-depleted cells and monitoring of receptor G protein activation by BRET, we identify Gq rather than Gi signaling to be responsible for SUCNR1-mediated effects on basic transcriptional regulation. Importantly, in primary human M2 macrophages, in which SUCNR1 is highly expressed, we demonstrate that physiological concentrations of extracellular succinate act through SUCNR1-activated Gq signaling to efficiently regulate transcription of immune function genes in a manner that hyperpolarizes their M2 versus M1 phenotype. Thus, sensing of stress-induced extracellular succinate by SUCNR1 is an important transcriptional regulator in human M2 macrophages through Gq signaling.",
keywords = "G protein, GPR91, Gq signaling, M2 macrophages, non-metabolite ligands, succinate, SUCNR1",
author = "Mette Trauelsen and Hiron, {Thomas K.} and Da Lin and Petersen, {Jacob E.} and Billy Breton and Husted, {Anna Sofie} and Hjorth, {Siv A.} and Asuka Inoue and Frimurer, {Thomas M.} and Michel Bouvier and O'Callaghan, {Chris A.} and Schwartz, {Thue W.}",
year = "2021",
doi = "10.1016/j.celrep.2021.109246",
language = "English",
volume = "35",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "11",

}

RIS

TY - JOUR

T1 - Extracellular succinate hyperpolarizes M2 macrophages through SUCNR1/GPR91-mediated Gq signaling

AU - Trauelsen, Mette

AU - Hiron, Thomas K.

AU - Lin, Da

AU - Petersen, Jacob E.

AU - Breton, Billy

AU - Husted, Anna Sofie

AU - Hjorth, Siv A.

AU - Inoue, Asuka

AU - Frimurer, Thomas M.

AU - Bouvier, Michel

AU - O'Callaghan, Chris A.

AU - Schwartz, Thue W.

PY - 2021

Y1 - 2021

N2 - Succinate functions both as a classical TCA cycle metabolite and an extracellular metabolic stress signal sensed by the mainly Gi-coupled succinate receptor SUCNR1. In the present study, we characterize and compare effects and signaling pathways activated by succinate and both classes of non-metabolite SUCNR1 agonists. By use of specific receptor and pathway inhibitors, rescue in G-protein-depleted cells and monitoring of receptor G protein activation by BRET, we identify Gq rather than Gi signaling to be responsible for SUCNR1-mediated effects on basic transcriptional regulation. Importantly, in primary human M2 macrophages, in which SUCNR1 is highly expressed, we demonstrate that physiological concentrations of extracellular succinate act through SUCNR1-activated Gq signaling to efficiently regulate transcription of immune function genes in a manner that hyperpolarizes their M2 versus M1 phenotype. Thus, sensing of stress-induced extracellular succinate by SUCNR1 is an important transcriptional regulator in human M2 macrophages through Gq signaling.

AB - Succinate functions both as a classical TCA cycle metabolite and an extracellular metabolic stress signal sensed by the mainly Gi-coupled succinate receptor SUCNR1. In the present study, we characterize and compare effects and signaling pathways activated by succinate and both classes of non-metabolite SUCNR1 agonists. By use of specific receptor and pathway inhibitors, rescue in G-protein-depleted cells and monitoring of receptor G protein activation by BRET, we identify Gq rather than Gi signaling to be responsible for SUCNR1-mediated effects on basic transcriptional regulation. Importantly, in primary human M2 macrophages, in which SUCNR1 is highly expressed, we demonstrate that physiological concentrations of extracellular succinate act through SUCNR1-activated Gq signaling to efficiently regulate transcription of immune function genes in a manner that hyperpolarizes their M2 versus M1 phenotype. Thus, sensing of stress-induced extracellular succinate by SUCNR1 is an important transcriptional regulator in human M2 macrophages through Gq signaling.

KW - G protein

KW - GPR91

KW - Gq signaling

KW - M2 macrophages

KW - non-metabolite ligands

KW - succinate

KW - SUCNR1

U2 - 10.1016/j.celrep.2021.109246

DO - 10.1016/j.celrep.2021.109246

M3 - Journal article

C2 - 34133934

AN - SCOPUS:85107987154

VL - 35

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 11

M1 - 109246

ER -

ID: 272642834