Receptor/beta-arrestin complex formation and the differential trafficking and resensitization of beta(2)-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 end ocytic vesicles in response to angiotensin II type lA receptor (AT(1A)R), b ut not beta2-adrenergic receptor (beta (2)AR), activation. The carboxyl-ter minal 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 b eta -arrestin redistribution to endosomes, whereas this property was lost f or an AT(1A)R bearing the beta (2)AR tall. Using beta (2)AR/AT(1A)R chimera s, we tested whether the beta (2)AR and AT(1A)R carboxyl-terminal tails, in part via their association with beta -arrestins, might regulate difference s in the intracellular trafficking and resensitization patterns of these re ceptors. 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 internaliz ation 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-i ndependent 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 A T(1A)R tall prevented beta (2)AR dephosphorylation and recycling. In contra st, although the beta (2)AR-tail promoted AT(1A)R recycling, the chimeric r eceptor remained both phosphorylated and desensitized, suggesting that rece ptor dephosphorylation is not a property common to ail receptors. In summar y, we show that the carboxyl-terminal tails of GPCRs not only contribute to regulating the patterns of receptor desensitization, but also modulate rec eptor intracellular trafficking and resensitization patterns.