The G protein-coupled receptor heterodimer network (GPCR-HetNet) and its hub components

G protein-coupled receptors (GPCRs) oligomerization has emerged as a vital characteristic of receptor structure. Substantial experimental evidence supports the existence of GPCR-GPCR interactions in a coordinated and cooperative manner. However, despite the current development of experimental techni...

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Autores: Borroto-Escuela, Dasiel O., Brito, Ismel, Romero-Fernandez, Wilber, Di Palma, Michael, Oflijan, Julia, Skieterska, Kamila, Duchou, Jolien, Craenenbroeck, Kathleen van, Suarez-Boomgaard, Diana, Rivera, Alicia, Guidolin, Diego, Agnati, Luigi Francesco, Fuxe, Kjell
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2014
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/132350
Acceso en línea:http://hdl.handle.net/10261/132350
Access Level:acceso abierto
Palabra clave:Oligomerization
Dimerization
Heteromers
Heterodimerization
Network
Hubs
Receptor–receptor interactions
Clusters
Architecture
G protein-coupled receptors
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spelling The G protein-coupled receptor heterodimer network (GPCR-HetNet) and its hub componentsBorroto-Escuela, Dasiel O.Brito, IsmelRomero-Fernandez, WilberDi Palma, MichaelOflijan, JuliaSkieterska, KamilaDuchou, JolienCraenenbroeck, Kathleen vanSuarez-Boomgaard, DianaRivera, AliciaGuidolin, DiegoAgnati, Luigi FrancescoFuxe, KjellOligomerizationDimerizationHeteromersHeterodimerizationNetworkHubsReceptor–receptor interactionsClustersArchitectureG protein-coupled receptorsG protein-coupled receptors (GPCRs) oligomerization has emerged as a vital characteristic of receptor structure. Substantial experimental evidence supports the existence of GPCR-GPCR interactions in a coordinated and cooperative manner. However, despite the current development of experimental techniques for large-scale detection of GPCR heteromers, in order to understand their connectivity it is necessary to develop novel tools to study the global heteroreceptor networks. To provide insight into the overall topology of the GPCR heteromers and identify key players, a collective interaction network was constructed. Experimental interaction data for each of the individual human GPCR protomers was obtained manually from the STRING and SCOPUS databases. The interaction data were used to build and analyze the network using Cytoscape software. The network was treated as undirected throughout the study. It is comprised of 156 nodes, 260 edges and has a scale-free topology. Connectivity analysis reveals a significant dominance of intrafamily versus interfamily connections. Most of the receptors within the network are linked to each other by a small number of edges. DRD2, OPRM, ADRB2, AA2AR, AA1R, OPRK, OPRD and GHSR are identified as hubs. In a network representation 10 modules/clusters also appear as a highly interconnected group of nodes. Information on this GPCR network can improve our understanding of molecular integration. GPCR-HetNet has been implemented in Java and is freely available at http://www.iiia.csic.es/~ismel/GPCR-Nets/index.html. © 2014 by the authors; licensee MDPI, Basel, Switzerland.This work has been supported by the Swedish Royal Academy of Sciences (Stiftelsen B. von Beskows Fond and Stiftelsen Hierta-Retzius stipendiefond) and Karolinska Institutets Forskningsstiftelser 2011 and 2012 to D.O.B.-E., by grants from the Swedish Medical Research Council (04X-715), Telethon TV3’s La Marató Foundation 2008 and Hjärnfonden to K.F., D.O.B.-E., I.B. and W.R.-F. belong to the “Academia de Biólogos Cubanos” group. Feliciano Calvo and Carmelo Million are acknowledged for their support during the GPCR heterodimer list preparation.Peer ReviewedMolecular Diversity Preservation InternationalRoyal Swedish Academy of SciencesFundació La Marató de TV3Karolinska InstituteSwedish Research CouncilConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2016201620142016info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/132350reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1323502026-05-22T06:33:51Z
dc.title.none.fl_str_mv The G protein-coupled receptor heterodimer network (GPCR-HetNet) and its hub components
title The G protein-coupled receptor heterodimer network (GPCR-HetNet) and its hub components
spellingShingle The G protein-coupled receptor heterodimer network (GPCR-HetNet) and its hub components
Borroto-Escuela, Dasiel O.
Oligomerization
Dimerization
Heteromers
Heterodimerization
Network
Hubs
Receptor–receptor interactions
Clusters
Architecture
G protein-coupled receptors
title_short The G protein-coupled receptor heterodimer network (GPCR-HetNet) and its hub components
title_full The G protein-coupled receptor heterodimer network (GPCR-HetNet) and its hub components
title_fullStr The G protein-coupled receptor heterodimer network (GPCR-HetNet) and its hub components
title_full_unstemmed The G protein-coupled receptor heterodimer network (GPCR-HetNet) and its hub components
title_sort The G protein-coupled receptor heterodimer network (GPCR-HetNet) and its hub components
dc.creator.none.fl_str_mv Borroto-Escuela, Dasiel O.
Brito, Ismel
Romero-Fernandez, Wilber
Di Palma, Michael
Oflijan, Julia
Skieterska, Kamila
Duchou, Jolien
Craenenbroeck, Kathleen van
Suarez-Boomgaard, Diana
Rivera, Alicia
Guidolin, Diego
Agnati, Luigi Francesco
Fuxe, Kjell
author Borroto-Escuela, Dasiel O.
author_facet Borroto-Escuela, Dasiel O.
Brito, Ismel
Romero-Fernandez, Wilber
Di Palma, Michael
Oflijan, Julia
Skieterska, Kamila
Duchou, Jolien
Craenenbroeck, Kathleen van
Suarez-Boomgaard, Diana
Rivera, Alicia
Guidolin, Diego
Agnati, Luigi Francesco
Fuxe, Kjell
author_role author
author2 Brito, Ismel
Romero-Fernandez, Wilber
Di Palma, Michael
Oflijan, Julia
Skieterska, Kamila
Duchou, Jolien
Craenenbroeck, Kathleen van
Suarez-Boomgaard, Diana
Rivera, Alicia
Guidolin, Diego
Agnati, Luigi Francesco
Fuxe, Kjell
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Royal Swedish Academy of Sciences
Fundació La Marató de TV3
Karolinska Institute
Swedish Research Council
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Oligomerization
Dimerization
Heteromers
Heterodimerization
Network
Hubs
Receptor–receptor interactions
Clusters
Architecture
G protein-coupled receptors
topic Oligomerization
Dimerization
Heteromers
Heterodimerization
Network
Hubs
Receptor–receptor interactions
Clusters
Architecture
G protein-coupled receptors
description G protein-coupled receptors (GPCRs) oligomerization has emerged as a vital characteristic of receptor structure. Substantial experimental evidence supports the existence of GPCR-GPCR interactions in a coordinated and cooperative manner. However, despite the current development of experimental techniques for large-scale detection of GPCR heteromers, in order to understand their connectivity it is necessary to develop novel tools to study the global heteroreceptor networks. To provide insight into the overall topology of the GPCR heteromers and identify key players, a collective interaction network was constructed. Experimental interaction data for each of the individual human GPCR protomers was obtained manually from the STRING and SCOPUS databases. The interaction data were used to build and analyze the network using Cytoscape software. The network was treated as undirected throughout the study. It is comprised of 156 nodes, 260 edges and has a scale-free topology. Connectivity analysis reveals a significant dominance of intrafamily versus interfamily connections. Most of the receptors within the network are linked to each other by a small number of edges. DRD2, OPRM, ADRB2, AA2AR, AA1R, OPRK, OPRD and GHSR are identified as hubs. In a network representation 10 modules/clusters also appear as a highly interconnected group of nodes. Information on this GPCR network can improve our understanding of molecular integration. GPCR-HetNet has been implemented in Java and is freely available at http://www.iiia.csic.es/~ismel/GPCR-Nets/index.html. © 2014 by the authors; licensee MDPI, Basel, Switzerland.
publishDate 2014
dc.date.none.fl_str_mv 2014
2016
2016
2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/132350
url http://hdl.handle.net/10261/132350
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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