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.
Keywords: G protein-coupled receptors; hub proteins; protein/protein interaction network; systems biology; β-arrestins.