Emerging paradigms of β-arrestin-dependent seven transmembrane receptor signaling

beta-Arrestins, originally discovered to desensitize activated seven transmembrane receptors (7TMRs; also known as G-protein-coupled receptors, GPCRs), are now well established mediators of receptor endocytosis, ubiquitylation and G protein-independent signaling. Recent global analyses of beta-arrestin interactions and beta-arrestin-dependent phosphorylation events have uncovered several previously unanticipated roles of beta-arrestins in a range of cellular signaling events. These findings strongly suggest that the functional roles of beta-arrestins are much broader than currently understood. Biophysical studies aimed at understanding multiple active conformations of the 7TMRs and the beta-arrestins have begun to unravel the mechanistic basis for the diverse functional capabilities of beta-arrestins in cellular signaling.