Heterodimers of serotonin receptor subtypes 2 are driven by 5-HT 2C protomers - Université Pierre et Marie Curie Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2017

Heterodimers of serotonin receptor subtypes 2 are driven by 5-HT 2C protomers

Luc Maroteaux
Stephane Doly

Résumé

The serotonin receptor subtypes 2 comprise 5-HT2A, 5-HT2B, and 5-HT2C, which are Gαq-coupled receptors and display distinct pharmacological properties. Although co-expressed in some brain regions and involved in various neurological disorders, their functional interactions have not yet been studied. We report that 5-HT2 receptors can form homo- and heterodimers when expressed alone or co-expressed in transfected cells. Co-immunoprecipitation and bioluminescence resonance energy transfer studies confirmed that 5-HT2C receptors interact with either 5-HT2A or 5-HT2B receptors. Although heterodimerization with 5-HT2C receptors does not alter 5-HT2C Gαq-dependent inositol phosphate signaling, 5-HT2A or 5-HT2B receptor-mediated signaling was totally blunted. This feature can be explained by a dominance of 5-HT2C on 5-HT2A and 5-HT2B receptor binding; in 5-HT2C-containing heterodimers, ligands bind and activate the 5-HT2C protomer exclusively. This dominant effect on the associated protomer was also observed in neurons, supporting the physiological relevance of 5-HT2 receptor heterodimerization in vivo Accordingly, exogenous expression of an inactive form of the 5-HT2C receptor in the locus ceruleus is associated with decreased 5-HT2A-dependent noradrenergic transmission. These data demonstrate that 5-HT2 receptors can form functionally asymmetric heterodimers in vitro and in vivo that must be considered when analyzing the physiological or pathophysiological roles of serotonin in tissues where 5-HT2 receptors are co-expressed.
Fichier principal
Vignette du fichier
JBCrev2_LM.pdf (4.29 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-01593841 , version 1 (27-09-2017)

Identifiants

Citer

Imane Moutkine, Emily Quentin, Bruno P. Guiard, Luc Maroteaux, Stephane Doly. Heterodimers of serotonin receptor subtypes 2 are driven by 5-HT 2C protomers. Journal of Biological Chemistry, 2017, 292 (15), pp.6352-6368. ⟨10.1074/jbc.M117.779041⟩. ⟨hal-01593841⟩
160 Consultations
110 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More