NDA@SZTAKI

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

D. Tóth, András

Gyombolai, Pál

Szalai, Bence

Várnai, Péter

Turu, Gábor

Hunyady, László

Elsevier

2017

QH3015 Molecular biology / molekuláris biológia

RC Internal medicine / belgyógyászat

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

angol

Article

PeerReviewed

info:eu-repo/semantics/article

text

http://real.mtak.hu/49000/1/MCE_D_16_00475R1_u.pdf

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

http://real.mtak.hu/49000/

http://dx.doi.org/10.1016/j.mce.2016.11.027

MTMT:3171969; doi:10.1016/j.mce.2016.11.027