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Article Dans Une Revue Traffic Année : 2018

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

Résumé

The signaling pathway of G protein-coupled receptors is strongly linked to their trafficking profile. Little is known about the molecular mechanisms involved in the vasopressin receptor V1b subtype (V1b R) 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 V1b R-mediated MAP kinase pathway. Using MEF cells Knocked-out for β-arrestins 1 and 2, we demonstrated that both β-arrestins 1 and 2 play a fundamental role in internalization and recycling of V1b R with a rapid and transient V1b R-β-arrestin interaction in contrast to a slow and long-lasting β-arrestin recruitment of the V2 vasopressin receptor subtype (V2 R). Using V1b R-V2 R chimeras and V1b R C-terminus truncations, we demonstrated the critical role of the V1b R C-terminus in its interaction with β-arrestins thereby regulating the receptor internalization and recycling kinetics in a phosphorylation-independent manner. In parallel, V1b R MAP kinase activation was dependent on arrestins and Src-kinase but independent on G proteins. Interestingly, Src interacted with hV1b R 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 V1b R involving both arrestins and Src kinase family.

Dates et versions

hal-02073197 , version 1 (19-03-2019)

Identifiants

Citer

Sanja Perkovska, Catherine Méjean, M. A. Ayoub, Juan Li, Floriane Hemery, et al.. V1b vasopressin receptor trafficking and signaling: Role of arrestins, G proteins and Src kinase. Traffic, 2018, 19 (1), pp.58-82. ⟨10.1111/tra.12535⟩. ⟨hal-02073197⟩
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