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...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2014-05-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1422-0067/15/5/8570 |
| _version_ | 1811232500299595776 |
|---|---|
| author | Dasiel O. Borroto-Escuela Ismel Brito Wilber Romero-Fernandez Michael Di Palma Julia Oflijan Kamila Skieterska Jolien Duchou Kathleen Van Craenenbroeck Diana Suárez-Boomgaard Alicia Rivera Diego Guidolin Luigi F. Agnati Kjell Fuxe |
| author_facet | Dasiel O. Borroto-Escuela Ismel Brito Wilber Romero-Fernandez Michael Di Palma Julia Oflijan Kamila Skieterska Jolien Duchou Kathleen Van Craenenbroeck Diana Suárez-Boomgaard Alicia Rivera Diego Guidolin Luigi F. Agnati Kjell Fuxe |
| author_sort | Dasiel O. Borroto-Escuela |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T11:03:53Z |
| format | Article |
| id | doaj.art-cf2ebfc70ef84853867744683952cd47 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-12T11:03:53Z |
| publishDate | 2014-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cf2ebfc70ef84853867744683952cd472022-12-22T03:35:52ZengMDPI AGInternational Journal of Molecular Sciences1422-00672014-05-011558570859010.3390/ijms15058570ijms15058570The G Protein-Coupled Receptor Heterodimer Network (GPCR-HetNet) and Its Hub ComponentsDasiel O. Borroto-Escuela0Ismel Brito1Wilber Romero-Fernandez2Michael Di Palma3Julia Oflijan4Kamila Skieterska5Jolien Duchou6Kathleen Van Craenenbroeck7Diana Suárez-Boomgaard8Alicia Rivera9Diego Guidolin10Luigi F. Agnati11Kjell Fuxe12Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, SwedenDepartment of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, SwedenDepartment of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, SwedenDepartment of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, SwedenDepartment of Physiology, Faculty of Medicine, University of Tartu, Tartu 50411, EstoniaLaboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST), Ghent University, 9000 Ghent, BelgiumLaboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST), Ghent University, 9000 Ghent, BelgiumLaboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST), Ghent University, 9000 Ghent, BelgiumDepartment of Cell Biology, School of Science, University of Málaga, 29071 Málaga, SpainDepartment of Cell Biology, School of Science, University of Málaga, 29071 Málaga, SpainDepartment of Molecular Medicine, University of Padova, Padova 35121, ItalyDepartment of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, SwedenDepartment of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, SwedenG 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.http://www.mdpi.com/1422-0067/15/5/8570G protein-coupled receptorsnetworkheterodimerizationheteromersdimerizationoligomerizationhubsreceptor–receptor interactionsclustersarchitecture |
| spellingShingle | Dasiel O. Borroto-Escuela Ismel Brito Wilber Romero-Fernandez Michael Di Palma Julia Oflijan Kamila Skieterska Jolien Duchou Kathleen Van Craenenbroeck Diana Suárez-Boomgaard Alicia Rivera Diego Guidolin Luigi F. Agnati Kjell Fuxe The G Protein-Coupled Receptor Heterodimer Network (GPCR-HetNet) and Its Hub Components International Journal of Molecular Sciences G protein-coupled receptors network heterodimerization heteromers dimerization oligomerization hubs receptor–receptor interactions clusters architecture |
| title | 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_short | The G Protein-Coupled Receptor Heterodimer Network (GPCR-HetNet) and Its Hub Components |
| title_sort | g protein coupled receptor heterodimer network gpcr hetnet and its hub components |
| topic | G protein-coupled receptors network heterodimerization heteromers dimerization oligomerization hubs receptor–receptor interactions clusters architecture |
| url | http://www.mdpi.com/1422-0067/15/5/8570 |
| work_keys_str_mv | AT dasieloborrotoescuela thegproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT ismelbrito thegproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT wilberromerofernandez thegproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT michaeldipalma thegproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT juliaoflijan thegproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT kamilaskieterska thegproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT jolienduchou thegproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT kathleenvancraenenbroeck thegproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT dianasuarezboomgaard thegproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT aliciarivera thegproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT diegoguidolin thegproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT luigifagnati thegproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT kjellfuxe thegproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT dasieloborrotoescuela gproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT ismelbrito gproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT wilberromerofernandez gproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT michaeldipalma gproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT juliaoflijan gproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT kamilaskieterska gproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT jolienduchou gproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT kathleenvancraenenbroeck gproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT dianasuarezboomgaard gproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT aliciarivera gproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT diegoguidolin gproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT luigifagnati gproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents AT kjellfuxe gproteincoupledreceptorheterodimernetworkgpcrhetnetanditshubcomponents |