Localization of the human oxytocin receptor in caveolin-1 enriched domains turns the receptor-mediated inhibition of cell growth into a proliferative response.
In this study, we investigated the functional role of the localization of human OTR in caveolin-1 enriched membrane domains. Biochemical fractionation of MDCK cells stably expressing the WT OTR-GFP indicated that only minor quantities of receptor are partitioned in caveolin-1 enriched domains. However, when fused to caveolin-2, the OTR protein proved to be exclusively localized in caveolin-1 enriched fractions, where it bound the agonist with increased affinity and efficiently coupled to Galpha(q/11). Interestingly, the chimeric protein was unable to undergo agonist-induced internalization and remained confined to the plasma membrane even after prolonged agonist exposure (120 min). A striking difference in receptor stimulation was observed when the OT-induced effect on cell proliferation was analysed: stimulation of the human WT OTR inhibited cell growth, whereas the chimeric protein had a proliferative effect. These data indicate that the localization of human OTR in caveolin-1 enriched microdomains radically alters its regulatory effects on cell growth; the fraction of OTR residing in caveolar structures may therefore play a crucial role in regulating cell proliferation.
Guzzi
Francesca
F
Department of Experimental and Environmental Medicine and Medical Biotechnologies, University of Milano-Bicocca, 20052 Monza, Italy.
Zanchetta
Deborah
D
Cassoni
Paola
P
Guzzi
Valeria
V
Francolini
Maura
M
Parenti
Marco
M
Chini
Bice
B
D000818:Animals; D019556:COS Cells; D051242:Caveolin 1; D051243:Caveolin 2; D022461:Caveolins / Q000032:analysis; D002455:Cell Division; D022163:Clathrin-Coated Vesicles / Q000737:chemistry; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D018045:Receptors, Oxytocin / Q000032:analysis* / Q000502:physiology
C495540:CAV1 protein, human; D051242:Caveolin 1; D051243:Caveolin 2; D022461:Caveolins; D018045:Receptors, Oxytocin; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins