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 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.
Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden. dasiel.borroto.escuela@ki.se.
Dasiel O
DO
Borroto-Escuela
Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden. ismel@iiia.csic.es.
Ismel
I
Brito
Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden. wromfdez@gmail.com.
Wilber
W
Romero-Fernandez
Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden. michael.dipalma@uniurb.it.
Michael
M
Di Palma
Department of Physiology, Faculty of Medicine, University of Tartu, Tartu 50411, Estonia. juliaofli@gmail.com.
Julia
J
Oflijan
Laboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST), Ghent University, 9000 Ghent, Belgium. kamila.skieterska@ugent.be.
Kamila
K
Skieterska
Laboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST), Ghent University, 9000 Ghent, Belgium. jolien.duchou@ugent.be.
Jolien
J
Duchou
Laboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST), Ghent University, 9000 Ghent, Belgium. kathleen.vancraenenbroeck@ugent.be.
Kathleen
K
Van Craenenbroeck
Department of Cell Biology, School of Science, University of Málaga, 29071 Málaga, Spain. boomgaard@uma.es.
Diana
D
Suárez-Boomgaard
Department of Cell Biology, School of Science, University of Málaga, 29071 Málaga, Spain. arivera@uma.es.
Alicia
A
Rivera
Department of Molecular Medicine, University of Padova, Padova 35121, Italy. diego.guidolin@unipd.it.
Diego
D
Guidolin
Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden. luigiagnati@tin.it.
Luigi F
LF
Agnati
Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden. Kjell.Fuxe@ki.se.
Kjell
K
Fuxe
D000465:Algorithms; D016000:Cluster Analysis; D030562:Databases, Protein; D019281:Dimerization; D006801:Humans; D020407:Internet; D053858:Metabolic Networks and Pathways; D008958:Models, Molecular; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism; D014584:User-Computer Interface
D043562:Receptors, G-Protein-Coupled