A Comprehensive View of the β-Arrestinome.
G protein-coupled receptors (GPCRs) are membrane receptors critically involved in sensing the environment and orchestrating physiological processes. As such, they transduce extracellular signals such as hormone, neurotransmitters, ions, and light into an integrated cell response. The intracellular trafficking, internalization, and signaling ability of ligand-activated GPCRs are controlled by arrestins, adaptor proteins that they interact with upon ligand binding. β-arrestins 1 and 2 in particular are now considered as hub proteins assembling multiprotein complexes to regulate receptor fate and transduce diversified cell responses. While more than 400 β-arrestin interaction partners have been identified so far, much remains to be learnt on how discrimination between so many binding partners is accomplished. Here, we gathered the interacting partners of β-arrestins through database mining and manual curation of the literature to map the β-arrestin interactome (β-arrestinome). We discussed several parameters that determine compatible (AND) or mutually exclusive (XOR) binding of β-arrestin interactors, such as structural constraints, intracellular abundance, or binding affinity.
INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France; «Biology and Bioinformatics of Signaling Systems (BIOS)» Group, CNRS, UMR7247, Nouzilly, France; Université François Rabelais, Tours, France; IFCE, Nouzilly, France.
Pascale
P
Crépieux
INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France; «Biology and Bioinformatics of Signaling Systems (BIOS)» Group, CNRS, UMR7247, Nouzilly, France; Université François Rabelais, Tours, France; IFCE, Nouzilly, France.
Anne
A
Poupon
INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France; «Biology and Bioinformatics of Signaling Systems (BIOS)» Group, CNRS, UMR7247, Nouzilly, France; Université François Rabelais, Tours, France; IFCE, Nouzilly, France.
Nathalie
N
Langonné-Gallay
INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France; «Biology and Bioinformatics of Signaling Systems (BIOS)» Group, CNRS, UMR7247, Nouzilly, France; Université François Rabelais, Tours, France; IFCE, Nouzilly, France.
Eric
E
Reiter
EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Javier
J
Delgado
EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Martin H
MH
Schaefer
INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France; «Biology and Bioinformatics of Signaling Systems (BIOS)» Group, CNRS, UMR7247, Nouzilly, France; Université François Rabelais, Tours, France; IFCE, Nouzilly, France.
Thomas
T
Bourquard
EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.
Luis
L
Serrano
EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Christina
C
Kiel
G protein-coupled receptors; hub proteins; protein/protein interaction network; systems biology; β-arrestins