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Localization of the human oxytocin receptor in caveolin-1 enriched domains turns the receptor-mediated inhibition of cell growth into a proliferative response

Oncogene volume 21, pages 1658–1667 (2002)Cite this article

Abstract

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 Gαq/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.

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References

  • Anderson RG . 1998 Ann. Rev. Biochem. 67: 199–225

  • Anderson RG, Kamen BA, Rothberg KG, Lacey SW . 1992 Science 255: 410–411

  • Bonifacino JS, Dell'Angelica EC . 1999 J. Cell Biol. 145: 923–926

  • Bussolati G, Cassoni P . 2001 Endocrinology 142: 1130–1136

  • Cassoni P, Sapino A, Fortunati N, Munaron L, Chini B, Bussolati G . 1997 Int. J. Cancer 72: 340–344

  • Cassoni P, Sapino A, Stella A, Fortunati N, Bussolati G . 1998 Int. J. Cancer 77: 695–700

  • Ceresa BP, Schmid SL . 2000 Curr. Opin. Cell Biol. 12: 204–210

  • Chini B, Mouillac B, Ala Y, Balestre M, Trumpp-Kallmeyer S, Hoflack J, Elands J, Hibert M, Manning M, Jard S, Barberis C . 1995 EMBO J. 14: 2176–2182

  • Chini B, Mouillac B, Balestre M, Trumpp-Kallmeyer S, Hoflack J, Hibert M, Andriolo M, Pupier S, Jard S, Barberis C . 1996 FEBS Letts. 397: 201–206

  • Cormack BP, Valdivia RH, Falkow S . 1996 Gene 173: 33–38

  • DeFea KA, Zalevsky J, Thoma MS, Dery O, Mullins RD, Bunnett NW . 2000 J. Cell Biol. 148: 1267–1281

  • Dessy C, Kelly RA, Balligand JL, Feron O . 2000 EMBO J. 19: 4272–4280

  • Elands J, Barberis C, Jard S . 1988 Am. J. Physiol. 254: (Suppl E) 31–38

  • Gimpl G, Fahrenholz F . 2000 Eur. J. Biochem. 267: 2483–2497

  • Gumbiner B, Stevenson B, Grimaldi A . 1988 J. Cell Biol. 107: 1575–1587

  • Gutkind JS . 1998 Oncogene 17: 1331–1342

  • Hailstones D, Sleer LS, Parton RG, Stanley KK . 1998 J. Lipid Res. 39: 369–379

  • Hansen SH, Sandvig K, van Deurs B . 1993 J. Cell Biol. 121: 61–72

  • Hoare S, Copland JA, Strakova Z, Ives K, Jeng YJ, Hellmich MR, Soloff MS . 1999 J. Biol. Chem. 274: 28682–28689

  • Kirk CJ, Guillon G, Balestre M, Jard S . 1986 Biochem. J. 240: 197–204

  • Klein U, Gimpl G, Fahrenholdz F . 1995 Biochem. 34: 13784–13793

  • Laemmli UK . 1970 Nature 227: 680–685

  • Lewis TS, Shapiro PS, Ahn NG . 1998 Adv. Cancer Res. 74: 49–139

  • Oakley RH, Laporte SA, Holt JA, Barak LS, Caron MG . 2001 J. Biol. Chem. 276: 19452–19460

  • Ohmichi M, Koike K, Nohara A, Kanda Y, Sakamoto Y, Zhang ZH, Hirota K, Miyake A . 1995 Endocrinol. 136: 2082–2087

  • Okamoto T, Schlegel A, Scherer PE, Lisanti MP . 1998 J. Biol. Chem. 273: 5419–5422

  • Ostrom RS, Violin JD, Coleman S, Insel PA . 2000 Mol. Pharmacol. 57: 1075–1079

  • Pierce KL, Luttrell LM, Lefkowitz RJ . 2001 Oncogene 20: 1532–1539

  • Rybin VO, Xu X, Lisanti MP, Steinberg SF . 2000 J. Biol. Chem. 275: 41447–41457

  • Scheiffele P, Verkade P, Fra AM, Virta H, Simons K, Ikonen E . 1998 J. Cell Biol. 140: 795–806

  • Simons K, Toomre D . 2000 Nature Rev. Mol. Cell. Biol. 1: 31–39

  • Strakova Z, Copland JA, Lolait SJ, Soloff MS . 1998 Am. J. Physiol. 274: (Suppl E) 634–641

  • Strakova Z, Soloff MS . 1997 Am. J. Physiol. 272: (Suppl E) 870–876

  • Thibonnier M, Auzan C, Madhun Z, Wilkins P, Berti-Mattera L, Clauser E . 1994 J. Biol. Chem. 269: 3304–3310

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Acknowledgements

We thank Dr V Pliska helpfully commenting on the binding assays and Prof N Borgese for critically reading the manuscript. This work was supported by a grant from the AIRC (Italian Association for Cancer Research) to B Chini and a MURST grant (Cofin 2000) to M Parenti.

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Author notes

  1. Francesca Guzzi and Deborah Zanchetta: F Guzzi and D Zanchetta contributed equally to this work

Authors and Affiliations

  1. Department of Experimental and Environmental Medicine and Medical Biotechnologies, University of Milano-Bicocca, Monza, 20052, Italy

    Francesca Guzzi & Marco Parenti

  2. CNR Cellular and Molecular Pharmacology Center, Milano, 20129, Italy

    Deborah Zanchetta, Valeria Guzzi & Bice Chini

  3. Department of Biomedical Sciences and Oncology, University of Torino, Torino, 10126, Italy

    Paola Cassoni

  4. Department of Pharmacology, University of Milano, Milano, 20129, Italy

    Maura Francolini

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  1. Francesca Guzzi
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  2. Deborah Zanchetta
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  4. Valeria Guzzi
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Correspondence to Bice Chini.

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Guzzi, F., Zanchetta, D., Cassoni, P. et al. Localization of the human oxytocin receptor in caveolin-1 enriched domains turns the receptor-mediated inhibition of cell growth into a proliferative response. Oncogene 21, 1658–1667 (2002). https://doi.org/10.1038/sj.onc.1205219

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