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

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 mediat...

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Autores: Navarro Brugal, Gemma|||0000-0003-4654-0873, Cordomí Montoya, Arnau|||0000-0002-3848-2928, Brugarolas, Marc, Moreno, Estefanía|||0000-0002-2491-5753, Aguinaga Andrés, David|||0000-0003-2506-7204, Pérez-Benito, Laura|||0000-0001-9607-9048, Ferré, Sergi|||0000-0002-1747-1779, Cortés, Antoni, Casadó, Vicent|||0000-0002-1764-3825, Mallol, Josefa, Canela, Enric I.|||0000-0003-4992-7440, Lluís, Carme, Pardo Carrasco, Leonardo|||0000-0003-1778-7420, McCormick, Peter J., Franco, Rafael|||0000-0003-2549-4919
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:253457
Acceso en línea:https://ddd.uab.cat/record/253457
https://dx.doi.org/urn:doi:10.1186/s12915-018-0491-x
Access Level:acceso abierto
Palabra clave:C-terminal domain
GPCR
Heterotetramer
BRET
Molecular modeling
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spelling Cross-communication between G and G in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domainNavarro Brugal, Gemma|||0000-0003-4654-0873Cordomí Montoya, Arnau|||0000-0002-3848-2928Brugarolas, MarcMoreno, Estefanía|||0000-0002-2491-5753Aguinaga Andrés, David|||0000-0003-2506-7204Pérez-Benito, Laura|||0000-0001-9607-9048Ferré, Sergi|||0000-0002-1747-1779Cortés, AntoniCasadó, Vicent|||0000-0002-1764-3825Mallol, JosefaCanela, Enric I.|||0000-0003-4992-7440Lluís, CarmePardo Carrasco, Leonardo|||0000-0003-1778-7420McCormick, Peter J.Franco, Rafael|||0000-0003-2549-4919C-terminal domainGPCRHeterotetramerBRETMolecular modelingG-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. 22018-01-0120182018-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/253457https://dx.doi.org/urn:doi:10.1186/s12915-018-0491-xreponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2015-74627-JINMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 BFU2015-64405-RAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 SAF2016-77830-Ropen accesshttp://purl.org/coar/access_right/c_abf2Aquest 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.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2534572026-06-06T12:50:31Z
dc.title.none.fl_str_mv Cross-communication between G and G in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain
title Cross-communication between G and G in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain
spellingShingle Cross-communication between G and G in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain
Navarro Brugal, Gemma|||0000-0003-4654-0873
C-terminal domain
GPCR
Heterotetramer
BRET
Molecular modeling
title_short Cross-communication between G and G in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain
title_full Cross-communication between G and G in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain
title_fullStr Cross-communication between G and G in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain
title_full_unstemmed Cross-communication between G and G in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain
title_sort Cross-communication between G and G in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain
dc.creator.none.fl_str_mv Navarro Brugal, Gemma|||0000-0003-4654-0873
Cordomí Montoya, Arnau|||0000-0002-3848-2928
Brugarolas, Marc
Moreno, Estefanía|||0000-0002-2491-5753
Aguinaga Andrés, David|||0000-0003-2506-7204
Pérez-Benito, Laura|||0000-0001-9607-9048
Ferré, Sergi|||0000-0002-1747-1779
Cortés, Antoni
Casadó, Vicent|||0000-0002-1764-3825
Mallol, Josefa
Canela, Enric I.|||0000-0003-4992-7440
Lluís, Carme
Pardo Carrasco, Leonardo|||0000-0003-1778-7420
McCormick, Peter J.
Franco, Rafael|||0000-0003-2549-4919
author Navarro Brugal, Gemma|||0000-0003-4654-0873
author_facet Navarro Brugal, Gemma|||0000-0003-4654-0873
Cordomí Montoya, Arnau|||0000-0002-3848-2928
Brugarolas, Marc
Moreno, Estefanía|||0000-0002-2491-5753
Aguinaga Andrés, David|||0000-0003-2506-7204
Pérez-Benito, Laura|||0000-0001-9607-9048
Ferré, Sergi|||0000-0002-1747-1779
Cortés, Antoni
Casadó, Vicent|||0000-0002-1764-3825
Mallol, Josefa
Canela, Enric I.|||0000-0003-4992-7440
Lluís, Carme
Pardo Carrasco, Leonardo|||0000-0003-1778-7420
McCormick, Peter J.
Franco, Rafael|||0000-0003-2549-4919
author_role author
author2 Cordomí Montoya, Arnau|||0000-0002-3848-2928
Brugarolas, Marc
Moreno, Estefanía|||0000-0002-2491-5753
Aguinaga Andrés, David|||0000-0003-2506-7204
Pérez-Benito, Laura|||0000-0001-9607-9048
Ferré, Sergi|||0000-0002-1747-1779
Cortés, Antoni
Casadó, Vicent|||0000-0002-1764-3825
Mallol, Josefa
Canela, Enric I.|||0000-0003-4992-7440
Lluís, Carme
Pardo Carrasco, Leonardo|||0000-0003-1778-7420
McCormick, Peter J.
Franco, Rafael|||0000-0003-2549-4919
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv C-terminal domain
GPCR
Heterotetramer
BRET
Molecular modeling
topic C-terminal domain
GPCR
Heterotetramer
BRET
Molecular modeling
description 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.
publishDate 2018
dc.date.none.fl_str_mv 2
2018-01-01
2018
2018-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/253457
https://dx.doi.org/urn:doi:10.1186/s12915-018-0491-x
url https://ddd.uab.cat/record/253457
https://dx.doi.org/urn:doi:10.1186/s12915-018-0491-x
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2015-74627-JIN
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 BFU2015-64405-R
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 SAF2016-77830-R
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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