β-Arrestins and G protein-coupled receptor trafficking.

Arrestins are adaptor proteins that function to regulate G protein-coupled receptor (GPCR) signaling and trafficking. There are four mammalian members of the arrestin family, two visual and two nonvisual. The visual arrestins (arrestin-1 and arrestin-4) are localized in rod and cone cells, respectively, and function to quench phototransduction by inhibiting receptor/G protein coupling. The nonvisual arrestins (β-arrestin1 and β-arrestin2, a.k.a. arrestin-2 and arrestin-3) are ubiquitously expressed and function to inhibit GPCR/G protein coupling and promote GPCR trafficking and arrestin-mediated signaling. Arrestin-mediated endocytosis of GPCRs requires the coordinated interaction of β-arrestins with clathrin, adaptor protein 2, and phosphoinositides such as PIP(2)/PIP(3). These interactions are facilitated by a conformational change in β-arrestin that is thought to occur upon binding to a phosphorylated activated GPCR. In this chapter, we provide an overview of the reagents and techniques used to study β-arrestin-mediated receptor trafficking.