Títol:
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Cross-communication between Gi and Gs in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain
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Autor/a:
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Navarro Brugal, Gemma; Cordomí, Arnau; Brugarolas Campillos, Marc; Moreno Guillén, Estefanía; Aguinaga Andrés, David; Pérez-Benito, Laura; Ferré, Sergi; Cortés Tejedor, Antonio; Casadó, Vicent; Mallol Montero, Josefa; Canela Campos, Enric I.; Lluís i Biset, Carme; Pardo, Leonardo; McCormick, Peter J.; Franco Fernández, Rafael
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Altres autors:
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Universitat de Barcelona |
Abstract:
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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. |
Matèries:
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-Adenosina -Receptors cel·lulars -Adenosine -Cell receptors |
Drets:
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cc-by (c) Navarro Brugal, Gemma et al., 2018
http://creativecommons.org/licenses/by/3.0/es |
Tipus de document:
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Article Article - Versió publicada |
Publicat per:
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BioMed Central
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