Navarro Brugal, GemmaCordomí, ArnauCasadó Anguera, VerònicaMoreno Guillén, EstefaníaCai, Ning-ShengCortes, AntoniCanela Campos, Enric I. (Enric Isidre), 1949-Dessauer, Carmen W.Casadó, VicentPardo, LeonardoLluís i Biset, CarmeFerré, Sergi2018-05-152018-05-152018-03-282041-1723https://hdl.handle.net/2445/122379G 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.12 p.application/pdfengcc-by (c) Navarro Brugal, Gemma et al., 2018http://creativecommons.org/licenses/by/3.0/esAdenosinaReceptors cel·lularsAdenosineCell receptorsinfo:eu-repo/semantics/article6803162018-05-15info:eu-repo/semantics/openAccess29593213