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Página principal > Artículos > Artículos publicados > Cross-communication between G and G in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain |
Fecha: | 2018 |
Resumen: | G-protein-coupled receptor (GPCR) heteromeric complexes have distinct properties from homomeric GPCRs, giving rise to new receptor functionalities. Adenosine receptors (AR or AR) can form AR-AR heteromers (A-AHet), and their activation leads to canonical G-protein-dependent (adenylate cyclase mediated) and -independent (β-arrestin mediated) signaling. Adenosine has different affinities for AR and AR, allowing the heteromeric receptor to detect its concentration by integrating the downstream G- and G-dependent signals. cAMP accumulation and β-arrestin recruitment assays have shown that, within the complex, activation of AR impedes signaling via AR. We examined the mechanism by which A-AHet integrates G- and G-dependent signals. AR blockade by AR in the A-AHet is not observed in the absence of AR activation by agonists, in the absence of the C-terminal domain of AR, or in the presence of synthetic peptides that disrupt the heteromer interface of A-AHet, indicating that signaling mediated by AR and AR is controlled by both G and G proteins. We identified a new mechanism of signal transduction that implies a cross-communication between G and G proteins guided by the C-terminal tail of the AR. This mechanism provides the molecular basis for the operation of the A-AHet as an adenosine concentration-sensing device that modulates the signals originating at both AR and AR. |
Ayudas: | Ministerio de Economía y Competitividad SAF2015-74627-JIN Ministerio de Economía y Competitividad BFU2015-64405-R Ministerio de Economía y Competitividad SAF2016-77830-R |
Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Materia: | C-terminal domain ; GPCR ; Heterotetramer ; BRET ; Molecular modeling |
Publicado en: | BMC biology, Vol. 16 (february 2018) , ISSN 1741-7007 |
15 p, 3.6 MB |