Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Functional Regulation of Dopamine D3 Receptor through Interaction with PICK1

  • Zheng, Mei (Pharmacology Laboratory, College of Pharmacy, Chonnam National University) ;
  • Zhang, Xiaohan (Pharmacology Laboratory, College of Pharmacy, Chonnam National University) ;
  • Min, Chengchun (Pharmacology Laboratory, College of Pharmacy, Chonnam National University) ;
  • Choi, Bo-Gil (Medicinal Chemistry Laboratory, College of Pharmacy, Chonnam National University) ;
  • Oh, In-Joon (Physical Pharmacy Laboratory, College of Pharmacy, Chonnam National University) ;
  • Kim, Kyeong-Man (Pharmacology Laboratory, College of Pharmacy, Chonnam National University)
  • Received : 2016.01.21
  • Accepted : 2016.03.17
  • Published : 2016.09.01
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Abstract

PICK1, a PDZ domain-containing protein, is known to increase the reuptake activities of dopamine transporters by increasing their expressions on the cell surface. Here, we report a direct and functional interaction between PICK1 and dopamine $D_3$ receptors ($D_3R$), which act as autoreceptors to negatively regulate dopaminergic neurons. PICK1 colocalized with both dopamine $D_2$ receptor ($D_2R$) and $D_3R$ in clusters but exerted different functional influences on them. The cell surface expression, agonist affinity, endocytosis, and signaling of $D_2R$ were unaffected by the coexpression of PICK1. On the other hand, the surface expression and tolerance of $D_3R$ were inhibited by the coexpression of PICK1. These findings show that PICK1 exerts multiple effects on $D_3R$ functions.

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References

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