Cross-communication between Gi and Gs in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain

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 (ade...

ver descrição completa

Detalhes bibliográficos
Autores: 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. (Enric Isidre), 1949-, Lluís i Biset, Carme, Pardo, Leonardo, McCormick, Peter J., Franco Fernández, Rafael
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/120611
Acesso em linha:https://hdl.handle.net/2445/120611
Access Level:acceso abierto
Palavra-chave:Adenosina
Receptors cel·lulars
Adenosine
Cell receptors
id ES_798d8e8043c73c477546fef8fc8092cf
oai_identifier_str oai:diposit.ub.edu:2445/120611
network_acronym_str ES
network_name_str España
repository_id_str
spelling Cross-communication between Gi and Gs in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domainNavarro Brugal, GemmaCordomí, ArnauBrugarolas Campillos, MarcMoreno Guillén, EstefaníaAguinaga Andrés, DavidPérez-Benito, LauraFerré, SergiCortés Tejedor, AntonioCasadó, VicentMallol Montero, JosefaCanela Campos, Enric I. (Enric Isidre), 1949-Lluís i Biset, CarmePardo, LeonardoMcCormick, Peter J.Franco Fernández, RafaelAdenosinaReceptors cel·lularsAdenosineCell receptorsBACKGROUND: 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.BioMed Central2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/120611Articles publicats en revistes (Bioquímica i Biomedicina Molecular)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/s12915-018-0491-xBmc Biology, 2018, vol. 16, num. 1, p. 24https://doi.org/10.1186/s12915-018-0491-xcc-by (c) Navarro Brugal, Gemma et al., 2018http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1206112026-05-27T06:46:51Z
dc.title.none.fl_str_mv Cross-communication between Gi and Gs in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain
title Cross-communication between Gi and Gs in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain
spellingShingle Cross-communication between Gi and Gs in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain
Navarro Brugal, Gemma
Adenosina
Receptors cel·lulars
Adenosine
Cell receptors
title_short Cross-communication between Gi and Gs in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain
title_full Cross-communication between Gi and Gs in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain
title_fullStr Cross-communication between Gi and Gs in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain
title_full_unstemmed Cross-communication between Gi and Gs in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain
title_sort Cross-communication between Gi and Gs in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain
dc.creator.none.fl_str_mv 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. (Enric Isidre), 1949-
Lluís i Biset, Carme
Pardo, Leonardo
McCormick, Peter J.
Franco Fernández, Rafael
author Navarro Brugal, Gemma
author_facet 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. (Enric Isidre), 1949-
Lluís i Biset, Carme
Pardo, Leonardo
McCormick, Peter J.
Franco Fernández, Rafael
author_role author
author2 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. (Enric Isidre), 1949-
Lluís i Biset, Carme
Pardo, Leonardo
McCormick, Peter J.
Franco Fernández, Rafael
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Adenosina
Receptors cel·lulars
Adenosine
Cell receptors
topic Adenosina
Receptors cel·lulars
Adenosine
Cell receptors
description 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.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/120611
url https://hdl.handle.net/2445/120611
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s12915-018-0491-x
Bmc Biology, 2018, vol. 16, num. 1, p. 24
https://doi.org/10.1186/s12915-018-0491-x
dc.rights.none.fl_str_mv cc-by (c) Navarro Brugal, Gemma et al., 2018
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Navarro Brugal, Gemma et al., 2018
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869411358240407552
score 15,300719

Registos relacionados