@article{162b4b4cf96c4874b27b6045efe09d9b,
title = "V1b vasopressin receptor trafficking and signaling: Role of arrestins, G proteins and Src kinase",
abstract = "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 (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 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 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.",
keywords = "BRET, DERET, FRET, G-protein-coupled receptor (GPCR), Src kinase, V and V vasopressin receptors, arrestin, biased signaling, intracellular trafficking, mitogen-activated protein kinase (MAPK), signal transduction",
author = "Sanja Perkovska and Catherine M{\'e}jean and Ayoub, {Mohammed Akli} and Juan Li and Floriane Hemery and Maith{\'e} Corbani and Nadine Laguette and Ventura, {Maria Angeles} and H{\'e}l{\`e}ne Orcel and Thierry Durroux and Bernard Mouillac and Christiane Mendre",
note = "Funding Information: This work was supported by research grants from CNRS and INSERM and was also made possible by the ARPEGE (Pharmacology-Screening-Interactome) platform facility at the Institut de G{\'e}nomique Fonc-tionnelle (Montpellier, France). We thank the Minist{\`e}re de l{\textquoteright}Enseignement Sup{\'e}rieur et de la Recherche for Ph.D grant of Dr Perkovska and CHU Montpellier for Dr Hemery{\textquoteright}s grant. We are also grateful to Pr Robert Lefkowitz for generously giving us MEF cells knocked-out for arrestins, to Dr Michel Auguet from IPSEN for BIM-46187, to Dr Serradeil-Legal from Sanofi-Aventis for SR149415, to Dr Claeysen for ps-Myc-hβ2AR, Cisbio Bioassays for SNAP-Flag receptor plasmids and Taglite technology, to Christian Barr{\`e}re for tsA cells. We are particularly grateful to Elisabeth Cassier for tools and advices provided all along the study. We also thank Muriel Asari, Dr Mathieu Fortier and Danny Mendre for iconography support. Funding Information: This work was supported by research grants from CNRS and INSERM and was also made possible by the ARPEGE (Pharmacology-Screening-Interactome) platform facility at the Institut de G{\'e}nomique Fonctionnelle (Montpellier, France). We thank the Minist{\`e}re de l{\textquoteright}Enseignement Sup{\'e}rieur et de la Recherche for Ph.D grant of Dr Perkovska and CHU Montpellier for Dr Hemery{\textquoteright}s grant. We are also grateful to Pr Robert Lefkowitz for generously giving us MEF cells knocked-out for arrestins, to Dr Michel Auguet from IPSEN for BIM-46187, to Dr Serradeil-Legal from Sanofi-Aventis for SR149415, to Dr Claeysen for ps-Myc-hβ2AR, Cisbio Bioassays for SNAP-Flag receptor plasmids and Taglite technology, to Christian Barr{\`e}re for tsA cells. We are particularly grateful to Elisabeth Cassier for tools and advices provided all along the study. We also thank Muriel Asari, Dr Mathieu Fortier and Danny Mendre for iconography support. The authors declare that they have no conflict of interest. SP designed, performed, analyzed experiments and wrote the paper; CMejean designed, performed and analyzed experiments; H.O., J.L., F.H., T.D. performed and analyzed experiments; M.C., N.L. and M.A.V. designed, performed and analyzed microscopy experiments; M.A.A. designed and analyzed BRET experiments; B.M. conceived, analyzed experiments and wrote the paper; M.A.V. gave ATT20 cells and 6Myc plasmids; CMendre conceived the study, designed, performed and analyzed experiments, coordinate the study and wrote the paper. All authors reviewed the results and approved the final version of the manuscript. The Editorial Process File is available in the online version of this article. Publisher Copyright: {\textcopyright} 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd",
year = "2018",
month = jan,
doi = "10.1111/tra.12535",
language = "English",
volume = "19",
pages = "58--82",
journal = "Traffic",
issn = "1398-9219",
publisher = "Blackwell Munksgaard",
number = "1",
}