β-Arrestins: Multitask Scaffolds Orchestrating the Where and When in Cell Signalling

The β-arrestins (β-arrs) were initially appreciated for the roles they play in the desensitization and endocytosis of G protein-coupled receptors (GPCRs). They are now also known to act as multifunctional adaptor proteins binding many non-receptor protein partners to control multiple signalling pathways. β-arrs therefore act as key regulatory hubs at the crossroads of external cell inputs and functional outputs in cellular processes ranging from gene transcription to cell growth, survival, cytoskeletal regulation, polarity, and migration. An increasing number of studies have also highlighted the scaffolding roles β-arrs play in vivo in both physiological and pathological conditions, which opens up therapeutic avenues to explore. In this introductory review chapter, we discuss the functional roles that β-arrs exert to control GPCR function, their dynamic scaffolding roles and how this impacts signal transduction events, compartmentalization of β-arrs, how β-arrs are regulated themselves, and how the combination of these events culminates in cellular regulation.