V1b vasopressin receptor trafficking and signaling  : role of arrestins, G proteins and Src kinase

The signaling pathway of G protein‐coupled receptors (GPCRs) is strongly linked to their trafficking profile. Little is known about the molecular mechanisms involved in the vasopressin receptor V1b subtype (V1bR) trafficking and its impact on receptor signaling and regulation. For this purpose, we investigated the role of β‐arrestins in receptor desensitization, internalization and recycling and attempted to dissect the V1bR‐mediated MAP Kinase pathway. Using β‐arrestin 1‐2 KO‐MEF cells, we demonstrated that both β‐arrestin 1 and 2 play a fundamental role in internalization and recycling of V1bR with a rapid and transient V1bR–β‐arrestin interaction in contrast to a slow and long‐lasting β‐arrestin recruitment of the V2 vasopressin receptor subtype (V2R). Using V1bR‐V2R chimeras and V1bR C‐terminus truncations, we demonstrated the critical role of the V1bR C‐terminus in its interaction with β‐arrestins thereby regulating the receptor internalization and recycling kinetics in a phosphorylation‐independent manner. In parallel, V1bR MAP kinase activation was dependent on arrestins and Src‐kinase but independent on G proteins. Interestingly, Src interacted with hV1bR at basal state and dissociated when receptor internalization occurred. Altogether, our data describe for the first time the trafficking profile and MAP Kinase pathway of V1bR involving both arrestins and Src kinase family.

Molecular mechanisms of the vasopressin receptor V1b s...

Source: Traffic - October 16, 2017 Category: Research Authors: Sanja Perkovska, Catherine M éjean, Mohammed Akli Ayoub, Juan Li, Floriane Hemery, Maithé Corbani, Nadine Laguette, Maria‐Angeles Ventura, Hélène Orcel, Thierry Durroux, Bernard Mouillac, Christiane Mendre Tags: ORIGINAL ARTICLE Source Type: research