Angiotensin type 1A receptor regulates β-arrestin binding of the β2-adrenergic receptor via heterodimerization

D. Tóth, András and Gyombolai, Pál and Szalai, Bence and Várnai, Péter and Turu, Gábor and Hunyady, László (2017) Angiotensin type 1A receptor regulates β-arrestin binding of the β2-adrenergic receptor via heterodimerization. MOLECULAR AND CELLULAR ENDOCRINOLOGY, 442. pp. 113-124. ISSN 0303-7207


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Heterodimerization between angiotensin type 1A receptor (AT1R) and β2-adrenergic receptor (β2AR) has been shown to modulate G protein-mediated effects of these receptors. Activation of G protein-coupled receptors (GPCRs) leads to β-arrestin binding, desensitization, internalization and G protein-independent signaling of GPCRs. Our aim was to study the effect of heterodimerization on β-arrestin coupling. We found that β-arrestin binding of β2AR is affected by activation of AT1Rs. Costimulation with angiotensin II and isoproterenol markedly enhanced the interaction between β2AR and β-arrestins, by prolonging the lifespan of β2AR-induced β-arrestin2 clusters at the plasma membrane. While candesartan, a conventional AT1R antagonist, had no effect on the β-arrestin2 binding to β2AR, TRV120023, a β-arrestin biased agonist, enhanced the interaction. These findings reveal a new crosstalk mechanism between AT1R and β2AR, and suggest that enhanced β-arrestin2 binding to β2AR can contribute to the pharmacological effects of biased AT1R agonists. © 2016

Item Type: Article
Uncontrolled Keywords: HETERODIMERIZATION; GPCR; BRET; Biased signaling; Arrestin
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3015 Molecular biology / molekuláris biológia
R Medicine / orvostudomány > RC Internal medicine / belgyógyászat
Depositing User: MTMT SWORD
Date Deposited: 15 Feb 2017 11:06
Last Modified: 15 Feb 2017 11:06

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