title: Basic Pharmacological and Structural Evidence for Class A G-Protein-Coupled Receptor Heteromerization.
abstract: Cell membrane receptors rarely work on isolation, often they form oligomeric complexes with other receptor molecules and they may directly interact with different proteins of the signal transduction machinery. For a variety of reasons, rhodopsin-like class A G-protein-coupled receptors (GPCRs) seem an exception to the general rule of receptor-receptor direct interaction. In fact, controversy surrounds their potential to form homo- hetero-dimers/oligomers with other class A GPCRs; in a sense, the field is going backward instead of forward. This review focuses on the convergent, complementary and telling evidence showing that homo- and heteromers of class A GPCRs exist in transfected cells and, more importantly, in natural sources. It is time to decide between questioning the occurrence of heteromers or, alternatively, facing the vast scientific and technical challenges that class A receptor-dimer/oligomer existence pose to Pharmacology and to Drug Discovery.
authors.affiliation: Departament de Bioquímica i Biomedicina Molecular, Facultat de Biología, Universitat de BarcelonaBarcelona, Spain; Centro de Investigación Biomédica en Red: Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos IIIMadrid, Spain; Institute of Biomedicine, University of BarcelonaBarcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
authors.affiliation: Instituto de Neurociencias del Principado de Asturias, Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de OviedoAsturias, Spain; Neurosciences Division, Centre for Applied Medical Research, University of NavarraPamplona, Spain; Instituto de Investigaciones Sanitarias de NavarraPamplona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Martínez-Pinilla
authors.affiliation: Centro de Investigación Biomédica en Red: Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos IIIMadrid, Spain; Neurosciences Division, Centre for Applied Medical Research, University of NavarraPamplona, Spain; Instituto de Investigaciones Sanitarias de NavarraPamplona, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Lanciego
authors.affiliation: Departament de Bioquímica i Biomedicina Molecular, Facultat de Biología, Universitat de BarcelonaBarcelona, Spain; Centro de Investigación Biomédica en Red: Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos IIIMadrid, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Navarro
keywords: GPCR; dimerization; dopamine receptor; heteromer; homodimer; ligands; mammalian receptor; signal transduction taste receptor