Fiche publication
Date publication
mai 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Dr VONESCH Jean-Luc
Tous les auteurs :
Faget L, Erbs E, Le Merrer J, Scherrer G, Matifas A, Benturquia N, Noble F, Decossas M, Koch M, Kessler P, Vonesch JL, Schwab Y, Kieffer BL, Massotte D
Lien Pubmed
Résumé
G-protein-coupled receptors (GPCRs) mediate numerous physiological functions and represent prime therapeutic targets. Receptor trafficking upon agonist stimulation is critical for GPCR function, but examining this process in vivo remains a true challenge. Using knock-in mice expressing functional fluorescent delta opioid receptors under the control of the endogenous promoter, we visualized in vivo internalization of this native GPCR upon physiological stimulation. We developed a paradigm in which animals were made dependent on morphine in a drug-paired context. When re-exposed to this context in a drug-free state, mice showed context-dependent withdrawal signs and activation of the hippocampus. Receptor internalization was transiently detected in a subset of CA1 neurons, uncovering regionally restricted opioid peptide release. Importantly, a pool of surface receptors always remained, which contrasts with the in vivo profile previously established for exogenous drug-induced internalization. Therefore, a distinct response is observed at the receptor level upon a physiological or pharmacological stimulation. Altogether, direct in vivo GPCR visualization enables mapping receptor stimulation promoted by a behavioral challenge and represents a powerful approach to study endogenous GPCR physiology.
Référence
J Neurosci. 2012 May 23;32(21):7301-10.
