Receptor/β-arrestin complex formation and the differential trafficking and resensitization of β2-adrenergic and angiotensin II type 1A receptors

beta -Arrestins target G protein-coupled receptors (GPCRs) for endocytosis via clathrin-coated vesicIes. beta -Arrestins also become detectable on endocytic vesicles in response to angiotensin II type lA receptor (AT(1A)R), but not beta2-adrenergic receptor (beta (2)AR), activation. The carboxyl-terminal talis of these receptors contribute directly to this phenotype, since a beta (2)AR bearing the AT(1A)R tail acquired the capacity to stimulate beta -arrestin redistribution to endosomes, whereas this property was lost for an AT(1A)R bearing the beta (2)AR tall. Using beta (2)AR/AT(1A)R chimeras, we tested whether the beta (2)AR and AT(1A)R carboxyl-terminal tails, in part via their association with beta -arrestins, might regulate differences in the intracellular trafficking and resensitization patterns of these receptors. In the present study, we find that beta -arrestin formed a stable complex with the AT(1A)R tail in endocytic vesicles and that the internalization of this complex was dynamin dependent. Internalization of the beta (2)AR chimera bearing the AT(1A)R tail was observed in the absence of agonist and was inhibited by a dominant-negative beta -arrestin1 mutant. Agonist-independent AT(1A)R internalization was also observed after beta -arrestin2 overexpression. After internalization, the beta (2)AR, but not the AT(1A)R, was dephosphorylated and recycled back to the cell surface. However, the AT(1A)R tall prevented beta (2)AR dephosphorylation and recycling. In contrast, although the beta (2)AR-tail promoted AT(1A)R recycling, the chimeric receptor remained both phosphorylated and desensitized, suggesting that receptor dephosphorylation is not a property common to ail receptors. In summary, we show that the carboxyl-terminal tails of GPCRs not only contribute to regulating the patterns of receptor desensitization, but also modulate receptor intracellular trafficking and resensitization patterns.