G protein-coupled receptor oligomerization revisited: functional and pharmacological perspectives.

Abstract : Most evidence indicates that, as for family C G protein-coupled receptors (GPCRs), family A GPCRs form homo- and heteromers. Homodimers seem to be a predominant species, with potential dynamic formation of higher-order oligomers, particularly tetramers. Although monomeric GPCRs can activate G proteins, the pentameric structure constituted by one GPCR homodimer and one heterotrimeric G protein may provide a main functional unit, and oligomeric entities can be viewed as multiples of dimers. It still needs to be resolved if GPCR heteromers are preferentially heterodimers or if they are mostly constituted by heteromers of homodimers. Allosteric mechanisms determine a multiplicity of possible unique pharmacological properties of GPCR homomers and heteromers. Some general mechanisms seem to apply, particularly at the level of ligand-binding properties. In the frame of the dimer-cooperativity model, the two-state dimer model provides the most practical method to analyze ligand-GPCR interactions when considering receptor homomers. In addition to ligand-binding properties, unique properties for each GPCR oligomer emerge in relation to different intrinsic efficacy of ligands for different signaling pathways (functional selectivity). This gives a rationale for the use of GPCR oligomers, and particularly heteromers, as novel targets for drug development. Herein, we review the functional and pharmacological properties of GPCR oligomers and provide some guidelines for the application of discrete direct screening and high-throughput screening approaches to the discovery of receptor-heteromer selective compounds.
Type de document :
Article dans une revue
Pharmacological Reviews, American Society for Pharmacology and Experimental Therapeutics, 2014, 66 (2), pp.413-34. 〈10.1124/pr.113.008052〉
Liste complète des métadonnées

Littérature citée [158 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-01067990
Contributeur : Mireille Bos <>
Soumis le : mercredi 24 septembre 2014 - 15:03:01
Dernière modification le : jeudi 25 janvier 2018 - 11:42:02
Document(s) archivé(s) le : vendredi 14 avril 2017 - 17:13:23

Fichier

 Accès restreint
Fichier visible le : jamais

Connectez-vous pour demander l'accès au fichier

Identifiants

Collections

Citation

Sergi Ferré, Vicent Casadó, Lakshmi Devi, Marta Filizola, Ralf Jockers, et al.. G protein-coupled receptor oligomerization revisited: functional and pharmacological perspectives.. Pharmacological Reviews, American Society for Pharmacology and Experimental Therapeutics, 2014, 66 (2), pp.413-34. 〈10.1124/pr.113.008052〉. 〈inserm-01067990〉

Partager

Métriques

Consultations de la notice

145