CARBOXYL-TERMINAL DOMAINS IN THE AVIAN BETA(1)-ADRENERGIC RECEPTOR THAT REGULATE AGONIST-PROMOTED ENDOCYTOSIS

Most G protein-coupled receptors, including the mammalian beta(2)-adre nergic receptor, are endocytosed to an intracellular, vesicular compar tment upon continued exposure to agonist. The long form of the avian b eta(1)-adrenergic receptor, which contains a carboxyl-terminal 59-amin o acid extension, does not undergo agonist-promoted endocytosis. We co nstructed and expressed turkey beta(1)-adrenergic receptor cDNAs with regularly spaced carboxyl-terminal truncations and studied their agoni st-promoted endocytosis. Removal of 34-86 amino acids from the carboxy l terminus of the turkey receptor allowed its efficient endocytosis, w ith optimal endocytosis observed upon re moval of 59 residues. Removal of only 18 residues allowed some endocytosis. A receptor that lacks t he entire carboxyl-terminal region (124 residues) was not endocytosed. We also constructed a chimeric hamster beta(2)-adrenergic recep tor w ith the added 59-residue carboxyl-terminal domain of the turkey recept or. The chimera was not significantly endocytosed. These data indicate that residues 450-465 in the carboxyl-terminal region of the beta(1)- adrenergic receptor can act independently to block agonist-promoted en docytosis and that other carboxyl-terminal structures nearer to the se venth membrane span are required for endocytosis.