Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Roles of Dopamine D2 Receptor Subregions in Interactions with β-Arrestin2

  • Zhang, Xiaohan (Pharmacology Laboratory, College of Pharmacy, Chonnam National University) ;
  • Choi, Bo-Gil (Medicinal Chemistry Laboratory, College of Pharmacy, Chonnam National University) ;
  • Kim, Kyeong-Man (Pharmacology Laboratory, College of Pharmacy, Chonnam National University)
  • Received : 2015.12.08
  • Accepted : 2016.01.05
  • Published : 2016.09.01
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Abstract

${\beta}$-Arrestins are one of the protein families that interact with G protein-coupled receptors (GPCRs). The roles of ${\beta}$-arrestins are multifaceted, as they mediate different processes including receptor desensitization, endocytosis, and G protein-independent signaling. Thus, determining the GPCR regions involved in the interactions with ${\beta}$-arrestins would be a preliminary step in understanding the molecular mechanisms involved in the selective direction of each function. In the current study, we determined the roles of the N-terminus, intracellular loops, and C-terminal tail of a representative GPCR in the interaction with ${\beta}$-arrestin2. For this, we employed dopamine $D_2$ and $D_3$ receptors ($D_2R$ and $D_3R$, respectively), since they display distinct agonist-induced interactions with ${\beta}$-arrestins. Our results showed that the second and third intracellular loops of $D_2R$ are involved in the agonist-induced translocation of ${\beta}$-arrestins toward plasma membranes. In contrast, the N- and C-termini of $D_2R$ exerted negative effects on the basal interaction with ${\beta}$-arrestins.

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References

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