2. Academic Validation
  3. Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling

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

  • Nat Commun. 2017 Feb 9;8:14335. doi: 10.1038/ncomms14335.
Chun-Hua Liu 1 2 3,  Zheng Gong 1,  Zong-Lai Liang 2,  Zhi-Xin Liu 1,  Fan Yang 2,  Yu-Jing Sun 1,  Ming-Liang Ma 1,  Yi-Jing Wang 1,  Chao-Ran Ji 2,  Yu-Hong Wang 1,  Mei-Jie Wang 1,  Fu-Ai Cui 1,  Amy Lin 4,  Wen-Shuai Zheng 2,  Dong-Fang He 1 2,  Chang-Xiu Qu 1 2,  Peng Xiao 1,  Chuan-Yong Liu 2,  Alex R B Thomsen 4,  Thomas Joseph Cahill 3rd 4,  Alem W Kahsai 4,  Fan Yi 5,  Kun-Hong Xiao 4 6,  Tian Xue 7,  Zhuan Zhou 8,  Xiao Yu 2,  Jin-Peng Sun 1
Affiliations

Affiliations

  • 1 Key Laboratory Experimental Teratology of the Ministry of Education, Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, Shandong 250012, China.
  • 2 Department of Physiology, Shandong University School of Medicine, Jinan, Shandong 250012, China.
  • 3 Department of Physiology, Taishan Medical University, Taian, Shandong 271000, China.
  • 4 Duke University, School of Medicine, Durham, North Carolina 27705, USA.
  • 5 Department of Pharmacology, Shandong University School of Medicine, Jinan, Shandong 250012, China.
  • 6 Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
  • 7 Hefei National Laboratory for Physical Science at Microscale, School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027, China.
  • 8 Laboratory of Cellular Biophysics and Neurodegeneration, Ying-Jie Conference Center, Peking University, Beijing 100871, China.
PMID: 28181498 DOI: 10.1038/ncomms14335
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.

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