V 1b vasopressin receptor trafficking and signaling: Role of arrestins, G proteins and Src kinase
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 V subtype (V R) trafficking and its impact on receptor signaling and regulation. For this purpose, we investigated...
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Published in | Traffic (Copenhagen, Denmark) Vol. 19; no. 1; pp. 58 - 82 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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England
01.01.2018
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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 V
subtype (V
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 V
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 V
R with a rapid and transient V
R-β-arrestin interaction in contrast to a slow and long-lasting β-arrestin recruitment of the V
vasopressin receptor subtype (V
R). Using V
R-V
R chimeras and V
R C-terminus truncations, we demonstrated the critical role of the V
R C-terminus in its interaction with β-arrestins thereby regulating the receptor internalization and recycling kinetics in a phosphorylation-independent manner. In parallel, V
R MAP kinase activation was dependent on arrestins and Src-kinase but independent on G proteins. Interestingly, Src interacted with hV
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 V
R involving both arrestins and Src kinase family. |
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AbstractList | 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 V
subtype (V
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 V
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 V
R with a rapid and transient V
R-β-arrestin interaction in contrast to a slow and long-lasting β-arrestin recruitment of the V
vasopressin receptor subtype (V
R). Using V
R-V
R chimeras and V
R C-terminus truncations, we demonstrated the critical role of the V
R C-terminus in its interaction with β-arrestins thereby regulating the receptor internalization and recycling kinetics in a phosphorylation-independent manner. In parallel, V
R MAP kinase activation was dependent on arrestins and Src-kinase but independent on G proteins. Interestingly, Src interacted with hV
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 V
R involving both arrestins and Src kinase family. 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 V 1b subtype (V 1b 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 V 1b 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 V 1b R with a rapid and transient V 1b R‐β‐arrestin interaction in contrast to a slow and long‐lasting β‐arrestin recruitment of the V 2 vasopressin receptor subtype (V 2 R). Using V 1b R‐V 2 R chimeras and V 1b R C‐terminus truncations, we demonstrated the critical role of the V 1b R C‐terminus in its interaction with β‐arrestins thereby regulating the receptor internalization and recycling kinetics in a phosphorylation‐independent manner. In parallel, V 1b R MAP kinase activation was dependent on arrestins and Src‐kinase but independent on G proteins. Interestingly, Src interacted with hV 1b 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 V 1b R involving both arrestins and Src kinase family. |
Author | Ayoub, Mohammed Akli Ventura, Maria-Angeles Durroux, Thierry Corbani, Maithé Hemery, Floriane Mendre, Christiane Perkovska, Sanja Li, Juan Orcel, Hélène Mouillac, Bernard Méjean, Catherine Laguette, Nadine |
Author_xml | – sequence: 1 givenname: Sanja surname: Perkovska fullname: Perkovska, Sanja organization: Université de Montpellier, Montpellier, France – sequence: 2 givenname: Catherine surname: Méjean fullname: Méjean, Catherine organization: Université de Montpellier, Montpellier, France – sequence: 3 givenname: Mohammed Akli surname: Ayoub fullname: Ayoub, Mohammed Akli organization: Biology Department, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates – sequence: 4 givenname: Juan surname: Li fullname: Li, Juan organization: Université de Montpellier, Montpellier, France – sequence: 5 givenname: Floriane surname: Hemery fullname: Hemery, Floriane organization: Université de Montpellier, Montpellier, France – sequence: 6 givenname: Maithé surname: Corbani fullname: Corbani, Maithé organization: Université de Montpellier, Montpellier, France – sequence: 7 givenname: Nadine surname: Laguette fullname: Laguette, Nadine organization: Université Paris Descartes, Sorbonne Paris Cité, Paris, France – sequence: 8 givenname: Maria-Angeles surname: Ventura fullname: Ventura, Maria-Angeles organization: Université Paris Descartes, Sorbonne Paris Cité, Paris, France – sequence: 9 givenname: Hélène surname: Orcel fullname: Orcel, Hélène organization: Université de Montpellier, Montpellier, France – sequence: 10 givenname: Thierry surname: Durroux fullname: Durroux, Thierry organization: Université de Montpellier, Montpellier, France – sequence: 11 givenname: Bernard surname: Mouillac fullname: Mouillac, Bernard organization: Université de Montpellier, Montpellier, France – sequence: 12 givenname: Christiane surname: Mendre fullname: Mendre, Christiane organization: Université de Montpellier, Montpellier, France |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29044966$$D View this record in MEDLINE/PubMed |
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CitedBy_id | crossref_primary_10_1016_j_prostaglandins_2018_05_003 crossref_primary_10_2147_OTT_S235066 crossref_primary_10_1038_s41467_017_02661_3 crossref_primary_10_1096_fj_202001729RR crossref_primary_10_3389_fendo_2019_00869 crossref_primary_10_1016_j_cell_2022_10_018 crossref_primary_10_1002_chem_202001446 crossref_primary_10_3390_ijms21228440 crossref_primary_10_3390_ijms22126489 crossref_primary_10_1073_pnas_2118847119 crossref_primary_10_1126_sciadv_abo7761 crossref_primary_10_1016_j_ejphar_2018_03_003 |
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Keywords | BRET V1b and V2 vasopressin receptors signal transduction mitogen-activated protein kinase (MAPK) Src kinase intracellular trafficking FRET G-protein-coupled receptor (GPCR) arrestin biased signaling DERET |
Language | English |
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Snippet | The signaling pathway of G protein-coupled receptors is strongly linked to their trafficking profile. Little is known about the molecular mechanisms involved... The signaling pathway of G protein‐coupled receptors is strongly linked to their trafficking profile. Little is known about the molecular mechanisms involved... |
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SubjectTerms | Animals beta-Arrestins - chemistry beta-Arrestins - metabolism Binding Sites GTP-Binding Proteins - metabolism HEK293 Cells Humans MAP Kinase Signaling System Mice Protein Binding Protein Transport Receptors, Vasopressin - metabolism src-Family Kinases - metabolism |
Title | V 1b vasopressin receptor trafficking and signaling: Role of arrestins, G proteins and Src kinase |
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