Heteromerization of Endogenous Mu and Delta Opioid Receptors Induces Ligand-Selective Co-Targeting to Lysosomes.
Fiche publication
Date publication
septembre 2020
Journal
Molecules (Basel, Switzerland)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ORY Stéphane
Tous les auteurs :
Derouiche L, Pierre F, Doridot S, Ory S, Massotte D
Lien Pubmed
Résumé
Increasing evidence indicates that native mu and delta opioid receptors can associate to form heteromers in discrete brain neuronal circuits. However, little is known about their signaling and trafficking. Using double-fluorescent knock-in mice, we investigated the impact of neuronal co-expression on the internalization profile of mu and delta opioid receptors in primary hippocampal cultures. We established ligand selective mu-delta co-internalization upon activation by 1-[[4-(acetylamino)phenyl]methyl]-4-(2-phenylethyl)-4-piperidinecarboxylic acid, ethyl ester (CYM51010), [d-Ala2, NMe-Phe4, Gly-ol5]enkephalin (DAMGO), and deltorphin II, but not (+)-4-[(α)-α-((2,5)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-,-diethylbenzamide (SNC80), morphine, or methadone. Co-internalization was driven by the delta opioid receptor, required an active conformation of both receptors, and led to sorting to the lysosomal compartment. Altogether, our data indicate that mu-delta co-expression, likely through heteromerization, alters the intracellular fate of the mu opioid receptor, which provides a way to fine-tune mu opioid receptor signaling. It also represents an interesting emerging concept for the development of novel therapeutic drugs and strategies.
Mots clés
delta opioid receptor, heteromer, internalization, lysosomes, mu opioid receptor, primary hippocampal culture
Référence
Molecules. 2020 Sep 30;25(19):