Evidence for functional pre-coupled complexes of receptor heteromers and adenylyl cyclase

G protein-coupled receptors (GPCRs), G proteins and adenylyl cyclase (AC) comprise one of the most studied transmembrane cell signaling pathways. However, it is unknown whether the ligand-dependent interactions between these signaling molecules are based on random collisions or the rearrangement of...

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Detalles Bibliográficos
Autores: Navarro Brugal, Gemma, Cordomí, Arnau, Casadó Anguera, Verònica, Moreno Guillén, Estefanía, Cai, Ning-Sheng, Cortes, Antoni, Canela Campos, Enric I. (Enric Isidre), 1949-, Dessauer, Carmen W., Casadó, Vicent, Pardo, Leonardo, Lluís i Biset, Carme, Ferré, Sergi
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/122379
Acceso en línea:https://hdl.handle.net/2445/122379
Access Level:acceso abierto
Palabra clave:Adenosina
Receptors cel·lulars
Adenosine
Cell receptors
Descripción
Sumario:G protein-coupled receptors (GPCRs), G proteins and adenylyl cyclase (AC) comprise one of the most studied transmembrane cell signaling pathways. However, it is unknown whether the ligand-dependent interactions between these signaling molecules are based on random collisions or the rearrangement of pre-coupled elements in a macromolecular complex. Furthermore, it remains controversial whether a GPCR homodimer coupled to a single heterotrimeric G protein constitutes a common functional unit. Using a peptide-based approach, we here report evidence for the existence of functional pre-coupled complexes of heteromers of adenosine A2A receptor and dopamine D2 receptor homodimers coupled to their cognate Gs and Gi proteins and to subtype 5 AC. We also demonstrate that this macromolecular complex provides the necessary frame for the canonical Gs-Gi interactions at the AC level, sustaining the ability of a Gi-coupled GPCR to counteract AC activation mediated by a Gs-coupled GPCR.