Angiotensin type 1A receptor regulates beta-arrestin binding of the beta(2)-adrenergic receptor via heterodimerization

作者：Toth Andras D; Gyombolai Pal; Szalai Bence; Varnai Peter; Turu Gabor; Hunyady Laszlo^*

来源：Molecular and Cellular Endocrinology, 2017, 442(C): 113-124.

DOI：10.1016/j.mce.2016.11.027

• GPCR
• Heterodimerization
• Arrestin
• BRET
• Biased signaling

Heterodimerization between angiotensin type 1A receptor (AT(1)R) and beta(2)-adrenergic receptor (beta(2)AR) has been shown to modulate G protein-mediated effects of these receptors. Activation of G protein-coupled receptors (GPCRs) leads to beta-arrestin binding, desensitization, internalization and G protein-independent signaling of GPCRs. Our aim was to study the effect of heterodimerization on beta-arrestin coupling. We found that beta-arrestin binding of beta(2)AR is affected by activation of AT(1)Rs. Costimulation with angiotensin II and isoproterenol markedly enhanced the interaction between beta(2)AR and beta-arrestins, by prolonging the lifespan of beta(2)AR-induced (beta-arresting clusters at the plasma membrane. While candesartan, a conventional AT(1)R antagonist, had no effect on the (beta-arresting2 binding to beta(2)AR, TRV120023, a beta-arrestin biased agonist, enhanced the interaction.
These findings reveal a new crosstalk mechanism between AT(1)R and beta(2)AR, and suggest that enhanced beta-arrestin2 binding to beta(2)AR can contribute to the pharmacological effects of biased AT(1)R agonists.

• 出版日期2017-2-15