Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling

Chun Hua Liu; Zheng Gong; Zong Lai Liang; Zhi Xin Liu; Fan Yang; Yu Jing Sun; Ming Liang Ma; Yi Jing Wang; Chao Ran Ji; Yu Hong Wang; Mei Jie Wang; Fu Ai Cui; Amy Lin; Wen Shuai Zheng; Dong Fang He; Chang Xiu Qu; Peng Xiao; Chuan Yong Liu; Alex R.B. Thomsen; Thomas Joseph Cahill; Alem W. Kahsai; Fan Yi; Kun Hong Xiao; Tian Xue; Zhuan Zhou; Xiao Yu; Jin Peng Sun

doi:10.1038/ncomms14335

Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling

Chun Hua Liu, Zheng Gong, Zong Lai Liang, Zhi Xin Liu, Fan Yang, Yu Jing Sun, Ming Liang Ma, Yi Jing Wang, Chao Ran Ji, Yu Hong Wang, Mei Jie Wang, Fu Ai Cui, Amy Lin, Wen Shuai Zheng, Dong Fang He, Chang Xiu Qu, Peng Xiao, Chuan Yong Liu, Alex R.B. Thomsen, Thomas Joseph CahillAlem W. Kahsai, Fan Yi, Kun Hong Xiao, Tian Xue, Zhuan Zhou, Xiao Yu, Jin Peng Sun

Molecular Pathobiology

Research output: Contribution to journal › Article › peer-review

Abstract

Acute hormone secretion triggered by G protein-coupled receptor (GPCR) activation underlies many fundamental physiological processes. GPCR signalling is negatively regulated by β-arrestins, adaptor molecules that also activate different intracellular signalling pathways. Here we reveal that TRV120027, a β-arrestin-1-biased agonist of the angiotensin II receptor type 1 (AT1R), stimulates acute catecholamine secretion through coupling with the transient receptor potential cation channel subfamily C 3 (TRPC3). We show that TRV120027 promotes the recruitment of TRPC3 or phosphoinositide-specific phospholipase C (PLCγ) to the AT1R-β-arrestin-1 signalling complex. Replacing the C-terminal region of β-arrestin-1 with its counterpart on β-arrestin-2 or using a specific TAT-P1 peptide to block the interaction between β-arrestin-1 and PLCγ abolishes TRV120027-induced TRPC3 activation. Taken together, our results show that the GPCR-arrestin complex initiates non-desensitized signalling at the plasma membrane by coupling with ion channels. This fast communication pathway might be a common mechanism of several cellular processes.

Original language	English (US)
Article number	14335
Journal	Nature communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms14335
State	Published - Feb 9 2017

ASJC Scopus subject areas

Physics and Astronomy(all)
Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)

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10.1038/ncomms14335

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Liu, C. H., Gong, Z., Liang, Z. L., Liu, Z. X., Yang, F., Sun, Y. J., Ma, M. L., Wang, Y. J., Ji, C. R., Wang, Y. H., Wang, M. J., Cui, F. A., Lin, A., Zheng, W. S., He, D. F., Qu, C. X., Xiao, P., Liu, C. Y., Thomsen, A. R. B., ... Sun, J. P. (2017). Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling. Nature communications, 8, Article 14335. https://doi.org/10.1038/ncomms14335

Liu, CH, Gong, Z, Liang, ZL, Liu, ZX, Yang, F, Sun, YJ, Ma, ML, Wang, YJ, Ji, CR, Wang, YH, Wang, MJ, Cui, FA, Lin, A, Zheng, WS, He, DF, Qu, CX, Xiao, P, Liu, CY, Thomsen, ARB, Cahill, TJ, Kahsai, AW, Yi, F, Xiao, KH, Xue, T, Zhou, Z, Yu, X & Sun, JP 2017, 'Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling', Nature communications, vol. 8, 14335. https://doi.org/10.1038/ncomms14335

@article{4bd8bb13937542918834d0320be23f95,

title = "Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling",

abstract = "Acute hormone secretion triggered by G protein-coupled receptor (GPCR) activation underlies many fundamental physiological processes. GPCR signalling is negatively regulated by β-arrestins, adaptor molecules that also activate different intracellular signalling pathways. Here we reveal that TRV120027, a β-arrestin-1-biased agonist of the angiotensin II receptor type 1 (AT1R), stimulates acute catecholamine secretion through coupling with the transient receptor potential cation channel subfamily C 3 (TRPC3). We show that TRV120027 promotes the recruitment of TRPC3 or phosphoinositide-specific phospholipase C (PLCγ) to the AT1R-β-arrestin-1 signalling complex. Replacing the C-terminal region of β-arrestin-1 with its counterpart on β-arrestin-2 or using a specific TAT-P1 peptide to block the interaction between β-arrestin-1 and PLCγ abolishes TRV120027-induced TRPC3 activation. Taken together, our results show that the GPCR-arrestin complex initiates non-desensitized signalling at the plasma membrane by coupling with ion channels. This fast communication pathway might be a common mechanism of several cellular processes.",

author = "Liu, {Chun Hua} and Zheng Gong and Liang, {Zong Lai} and Liu, {Zhi Xin} and Fan Yang and Sun, {Yu Jing} and Ma, {Ming Liang} and Wang, {Yi Jing} and Ji, {Chao Ran} and Wang, {Yu Hong} and Wang, {Mei Jie} and Cui, {Fu Ai} and Amy Lin and Zheng, {Wen Shuai} and He, {Dong Fang} and Qu, {Chang Xiu} and Peng Xiao and Liu, {Chuan Yong} and Thomsen, {Alex R.B.} and Cahill, {Thomas Joseph} and Kahsai, {Alem W.} and Fan Yi and Xiao, {Kun Hong} and Tian Xue and Zhuan Zhou and Xiao Yu and Sun, {Jin Peng}",

note = "Funding Information: We acknowledge support from the National Key Basic Research Program of China (2013CB967700 to X.Y. and T.X.), the National Key Research and Development Program of China (2016YFA0400900 to T.X.), the National Natural Science Foundation of China (31470789, 31611540337, 31271505 to J.-P.S.; 31471102, 31671197 to X.Y.; 81371066, 91432104 and 31322024 to T.X.), the China Postdoctoral Science Foundation (2015M582082 to P.X.), the Shandong Natural Science Fund for Distinguished Young Scholars(JQ201320 to X.Y. and JQ201517 to J.-P.S.), the Fundamental Research Fund of Shandong University (2014JC029 to X.Y.) and the Program for Changjiang Scholars and Innovative Research Team in University (IRT13028). Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = feb,

day = "9",

doi = "10.1038/ncomms14335",

language = "English (US)",

volume = "8",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling

AU - Liu, Chun Hua

AU - Gong, Zheng

AU - Liang, Zong Lai

AU - Liu, Zhi Xin

AU - Yang, Fan

AU - Sun, Yu Jing

AU - Ma, Ming Liang

AU - Wang, Yi Jing

AU - Ji, Chao Ran

AU - Wang, Yu Hong

AU - Wang, Mei Jie

AU - Cui, Fu Ai

AU - Lin, Amy

AU - Zheng, Wen Shuai

AU - He, Dong Fang

AU - Qu, Chang Xiu

AU - Xiao, Peng

AU - Liu, Chuan Yong

AU - Thomsen, Alex R.B.

AU - Cahill, Thomas Joseph

AU - Kahsai, Alem W.

AU - Yi, Fan

AU - Xiao, Kun Hong

AU - Xue, Tian

AU - Zhou, Zhuan

AU - Yu, Xiao

AU - Sun, Jin Peng

N1 - Funding Information: We acknowledge support from the National Key Basic Research Program of China (2013CB967700 to X.Y. and T.X.), the National Key Research and Development Program of China (2016YFA0400900 to T.X.), the National Natural Science Foundation of China (31470789, 31611540337, 31271505 to J.-P.S.; 31471102, 31671197 to X.Y.; 81371066, 91432104 and 31322024 to T.X.), the China Postdoctoral Science Foundation (2015M582082 to P.X.), the Shandong Natural Science Fund for Distinguished Young Scholars(JQ201320 to X.Y. and JQ201517 to J.-P.S.), the Fundamental Research Fund of Shandong University (2014JC029 to X.Y.) and the Program for Changjiang Scholars and Innovative Research Team in University (IRT13028). Publisher Copyright: © 2017 The Author(s).

PY - 2017/2/9

Y1 - 2017/2/9

N2 - Acute hormone secretion triggered by G protein-coupled receptor (GPCR) activation underlies many fundamental physiological processes. GPCR signalling is negatively regulated by β-arrestins, adaptor molecules that also activate different intracellular signalling pathways. Here we reveal that TRV120027, a β-arrestin-1-biased agonist of the angiotensin II receptor type 1 (AT1R), stimulates acute catecholamine secretion through coupling with the transient receptor potential cation channel subfamily C 3 (TRPC3). We show that TRV120027 promotes the recruitment of TRPC3 or phosphoinositide-specific phospholipase C (PLCγ) to the AT1R-β-arrestin-1 signalling complex. Replacing the C-terminal region of β-arrestin-1 with its counterpart on β-arrestin-2 or using a specific TAT-P1 peptide to block the interaction between β-arrestin-1 and PLCγ abolishes TRV120027-induced TRPC3 activation. Taken together, our results show that the GPCR-arrestin complex initiates non-desensitized signalling at the plasma membrane by coupling with ion channels. This fast communication pathway might be a common mechanism of several cellular processes.

AB - Acute hormone secretion triggered by G protein-coupled receptor (GPCR) activation underlies many fundamental physiological processes. GPCR signalling is negatively regulated by β-arrestins, adaptor molecules that also activate different intracellular signalling pathways. Here we reveal that TRV120027, a β-arrestin-1-biased agonist of the angiotensin II receptor type 1 (AT1R), stimulates acute catecholamine secretion through coupling with the transient receptor potential cation channel subfamily C 3 (TRPC3). We show that TRV120027 promotes the recruitment of TRPC3 or phosphoinositide-specific phospholipase C (PLCγ) to the AT1R-β-arrestin-1 signalling complex. Replacing the C-terminal region of β-arrestin-1 with its counterpart on β-arrestin-2 or using a specific TAT-P1 peptide to block the interaction between β-arrestin-1 and PLCγ abolishes TRV120027-induced TRPC3 activation. Taken together, our results show that the GPCR-arrestin complex initiates non-desensitized signalling at the plasma membrane by coupling with ion channels. This fast communication pathway might be a common mechanism of several cellular processes.

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U2 - 10.1038/ncomms14335

DO - 10.1038/ncomms14335

M3 - Article

C2 - 28181498

AN - SCOPUS:85012050956

SN - 2041-1723

VL - 8

JO - Nature communications

JF - Nature communications

M1 - 14335

ER -

Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling

Abstract

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