β-Arrestins and G Protein-Coupled Receptor Trafficking

Abstract

Non-visual arrestins (β-arrestin-1 and β-arrestin-2) are adaptor proteins that function to regulate G protein-coupled receptor (GPCR) signaling and trafficking. β-arrestins are ubiquitously expressed and function to inhibit GPCR/G protein coupling, a process called desensitization, and promote GPCR trafficking and arrestin-mediated signaling. β-arrestin-mediated endocytosis of GPCRs requires the coordinated interaction of β-arrestins with clathrin, adaptor protein 2 (AP2) and phosphoinositides. 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 review, we provide an overview of the key interactions involved in β-arrestin-mediated trafficking of GPCRs.

Phosphorylation of the Deubiquitinase USP20 by Protein Kinase A Regulates Post-endocytic Trafficking of β2 Adrenergic Receptors to Autophagosomes during Physiological Stress

“…(47). However, upon localizing to endosomes, studies so far predict a direct route for degradation to lysosomes via late endosomes.…”

Spatial and Temporal Aspects of Signaling by G-Protein–Coupled Receptors

“…This process occurs in a sequence of events because (b-)arrestin binding requires both the active structure of the receptor and phosphorylation by a GRK (Krasel et al, 2005). For nonvisual GPCRs, this process is generally linked to receptor assembly in clathrin-coated pits and subsequent internalization into clathrin-coated vesicles because b-arrestins serve as adapters between GPCRs and clathrin as well as b-adaptin, the b-subunit of the clathrin binding adapter AP2 (Goodman et al, 1996;Tian et al, 2014). However, it should be noted that some GPCRs do not recruit b-arrestins, and that internalization may also occur in a b-arrestin-independent manner (Blaukat et al, 1996;Zhang et al, 1996;Pals-Rylaarsdam et al, 1997;van Koppen and Jakobs, 2004).…”

Ethanol extracts of <i>Aster yomena</i> (Kitam.) Honda inhibit adipogenesis through the activation of the AMPK signaling pathway in 3T3-L1 preadipocytes

“…In addition, EEAY also reduced the expression of adipocyte markers aP2 and leptin on the 3T3-L1 cells. aP2 is a carrier protein that can trigger the accumulation of lipid droplets in the cytoplasm of differentiating adipocytes (36,37), and leptin upregulates the adipocyte genes involved in lipid oxidation, enhancing lipid accumulation in the adipocytes (38,39); therefore, our results also suggest that EEAY strongly suppress the de novo synthesis of TGs and differentiation of adipocytes.…”