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

Research output: Contribution to journalArticlepeer-review


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 languageEnglish (US)
Article number14335
JournalNature communications
StatePublished - Feb 9 2017

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


Dive into the research topics of 'Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling'. Together they form a unique fingerprint.

Cite this