Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling.
Nat Commun
; 8: 14335, 2017 02 09.
Article
en En
| MEDLINE
| ID: mdl-28181498
ABSTRACT
Acute hormone secretion triggered by G protein-coupled receptor (GPCR) activation underlies many fundamental physiological processes. GPCR signalling is negatively regulated by ß-arrestins, adaptor molecules that also activate different intracellular signalling pathways. Here we reveal that TRV120027, a ß-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-ß-arrestin-1 signalling complex. Replacing the C-terminal region of ß-arrestin-1 with its counterpart on ß-arrestin-2 or using a specific TAT-P1 peptide to block the interaction between ß-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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Catecolaminas
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Receptor de Angiotensina Tipo 1
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Canales Catiónicos TRPC
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Beta-Arrestina 1
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Arrestina beta 2
Límite:
Animals
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Humans
Idioma:
En
Año:
2017
Tipo del documento:
Article