2026-04-17T17:06:24Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1206112025-12-04T21:16:26Zcom_2072_1057col_2072_478781col_2072_478917

00925njm 22002777a 4500 dc Navarro Brugal, Gemma author Cordomí, Arnau author Brugarolas Campillos, Marc author Moreno Guillén, Estefanía author Aguinaga Andrés, David author Pérez-Benito, Laura author Ferré, Sergi author Cortés Tejedor, Antonio author Casadó, Vicent author Mallol Montero, Josefa author Canela Campos, Enric I. (Enric Isidre), 1949- author Lluís i Biset, Carme author Pardo, Leonardo author McCormick, Peter J. author Franco Fernández, Rafael author 2018-03-12T12:29:24Z 2018-03-12T12:29:24Z 2018-02-28 2018-03-12T12:29:24Z BACKGROUND: G-protein-coupled receptor (GPCR) heteromeric complexes have distinct properties from homomeric GPCRs, giving rise to new receptor functionalities. Adenosine receptors (A1R or A2AR) can form A1R-A2AR heteromers (A1-A2AHet), and their activation leads to canonical G-protein-dependent (adenylate cyclase mediated) and -independent (β-arrestin mediated) signaling. Adenosine has different affinities for A1R and A2AR, allowing the heteromeric receptor to detect its concentration by integrating the downstream Gi- and Gs-dependent signals. cAMP accumulation and β-arrestin recruitment assays have shown that, within the complex, activation of A2AR impedes signaling via A1R. RESULTS: We examined the mechanism by which A1-A2AHet integrates Gi- and Gs-dependent signals. A1R blockade by A2AR in the A1-A2AHet is not observed in the absence of A2AR activation by agonists, in the absence of the C-terminal domain of A2AR, or in the presence of synthetic peptides that disrupt the heteromer interface of A1-A2AHet, indicating that signaling mediated by A1R and A2AR is controlled by both Gi and Gs proteins. CONCLUSIONS: We identified a new mechanism of signal transduction that implies a cross-communication between Gi and Gs proteins guided by the C-terminal tail of the A2AR. This mechanism provides the molecular basis for the operation of the A1-A2AHet as an adenosine concentration-sensing device that modulates the signals originating at both A1R and A2AR. Adenosina Receptors cel·lulars Adenosine Cell receptors Cross-communication between Gi and Gs in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain