HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 6, 4592-4601, February 11, 2005

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 280/6/4592    most recent M406199200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mouillet-Richard, S. Articles by Kellermann, O. Search for Related Content PubMed PubMed Citation Articles by Mouillet-Richard, S. Articles by Kellermann, O. Social Bookmarking                      What's this?

Modulation of Serotonergic Receptor Signaling and Cross-talk by Prion Protein^*

Sophie Mouillet-Richard, Mathéa Pietri, Benoît Schneider, Catherine Vidal¶, Vincent Mutel||, Jean-Marie Launay**, and Odile Kellermann

From the Différenciation cellulaire et prions, CNRS UPR 1983 Institut André Lwoff, 7 rue Guy Môquet, BP8, 94801 Villejuif Cedex, France and Institut Pasteur, Département de Biologie Cellulaire et Infections, 25/28 rue du Docteur Roux, 75724 Paris Cedex 15, France, ^¶Service de neurovirologie, Commissariat à l'Energie Atomique, 18 route du Panorama, 92265 Fontenay aux Roses, France, ^||Pharma Research Department, F. Hoffmann-La-Roche Ltd., CH-4070 Basel, Switzerland, and ^**Service de Biochimie, IFR6, Hôpital Lariboisière, 75009 Paris and EA3621, Faculté de Pharmacie Paris V, France

The inducible serotonergic 1C11^5-HT cell line expresses a defined set of serotonergic receptors of the 5-HT_2B, 5-HT_1B/D, and 5-HT_2A subtypes, which sustain a regulation of serotonergic associated functions through G-protein-dependent signaling. 1C11^5-HT cells have been instrumental to assign a signaling function to the cellular prion protein PrP^C. Here, we establish that antibody-mediated ligation of PrP^C concomitant to agonist stimulation of 5-HT receptors modulates the couplings of all three serotonergic receptors present on 1C11^5-HT cells. Specific impacts of PrP antibodies were monitored depending on the receptor and pathway considered. PrP^C ligation selectively cancels the 5-HT_2A-PLC response, decreases the 5-HT_1B/D negative coupling to adenylate cyclase, and potentiates the 5-HT_2B-PLA2 coupling. As a result, PrP^C ligation disturbs the functional interactions occurring between the signaling pathways of the three receptor subtypes. In 1C11^5-HT cells, antagonizing cross-talks arising from 5-HT_2B and 5-HT_2A receptors control the 5-HT_1B/D function. PrP^C ligation reinforces the negative regulation exerted by 5-HT_2B on 5-HT_1B/D receptors. On the other hand it abrogates the blocking action of 5-HT_2A on the regulatory loop linking 5-HT_1B/D receptors. We propose that the ligation of PrP^C affects the potency or dynamics of G-protein activation by agonist-bound serotonergic receptors. Finally, the PrP^C-dependent modulation of 5-HT receptor couplings is restricted to 1C11^5-HT cells expressing a complete serotonergic phenotype. It critically involves a PrP^C-caveolin platform implemented on the neurites of 1C11^5-HT cells during differentiation. Our findings define PrP^C as a modulator of 5-HT receptor coupling to G-proteins and thereby as a protagonist contributing to the homeostasis of serotonergic neurons. They provide a foundation for uncovering the impact of prion infection on serotonergic functions.

Received for publication, June 3, 2004 , and in revised form, December 7, 2004.

^* This work is supported by grants from the Groupement d'intérêt scientifique "infections à prions." The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1.

To whom correspondence should be addressed. Tel.: 33-1-49-58-33-33; Fax: 33-1-49-58-33-29; E-mail: mouillet{at}vjf.cnrs.fr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. Linden, V. R. Martins, M. A. M. Prado, M. Cammarota, I. Izquierdo, and R. R. Brentani Physiology of the Prion Protein Physiol Rev, April 1, 2008; 88(2): 673 - 728. [Abstract] [Full Text] [PDF]

				S. MOUILLET-RICHARD, B. SCHNEIDER, E. PRADINES, M. PIETRI, M. ERMONVAL, J. GRASSI, J. G. RICHARDS, V. MUTEL, J.-M. LAUNAY, and O. KELLERMANN Cellular Prion Protein Signaling in Serotonergic Neuronal Cells Ann. N.Y. Acad. Sci., January 1, 2007; 1096(1): 106 - 119. [Abstract] [Full Text] [PDF]

				B. SCHNEIDER, M. PIETRI, S. MOUILLET-RICHARD, M. ERMONVAL, V. MUTEL, J.-M. LAUNAY, and O. KELLERMANN Control of Bioamine Metabolism by 5-HT2B and {alpha}1D Autoreceptors through Reactive Oxygen Species and Tumor Necrosis Factor-{alpha} Signaling in Neuronal Cells Ann. N.Y. Acad. Sci., December 1, 2006; 1091(1): 123 - 141. [Abstract] [Full Text] [PDF]