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Insensitivity of the human beta1-adrenergic receptor to agonist-mediated degradation intracellular trafficking and role of the C-terminus



Insensitivity of the human beta1-adrenergic receptor to agonist-mediated degradation intracellular trafficking and role of the C-terminus



FASEB Journal 17(4-5): Abstract No 142 7



The human (1AR is more resistant to agonist-mediated down-regulation than (2AR. To test whether the difference is due to a divergence in endosomal trafficking and motifs in the (AR c-terminus (ct), wild type (wt) (ARs and (1/(2ct and (2/(1ct chimeras were expressed, and their internalization, recycling, down-regulation and turnover determined. Cells treated with agonist for 24 h were assayed for (AR binding activity and protein by Western blotting. Whereas (2AR and (1/(2ct were down-regulated and degraded, (1AR and (2/(1ct were up-regulated. In 30-min agonist-treated cells, internalization was (2AR>(1/(2ct>(2/(1ct((1AR, the same order as for down-regulation. The former did not determine the latter as overexpression of arrestin-2 increased (1AR internalization without altering its resistance to down-regulation. Basal turnover rates of both wt (ARs were similar; agonist treatment increased (2AR but not (1AR turnover as well as that of (1/(2ct but not (2/(1ct. Blocking (AR trafficking to lysosomes with bafilomycin had no effect on basal (1AR or (2AR turnover but blocked agonist-stimulated (2AR turnover. Finally, monensin blocked recycling of internalized (2AR but not (1AR; and recycling of (1/(2ct more than that of (2/(1ct. We conclude that the (2AR ct contributes to, whereas the (1AR ct attenuates receptor degradation, most likely by directing each subtype to distinct endosomal pathways.

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Accession: 035148595

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