Journal
BIOMOLECULES & THERAPEUTICS
Volume 24, Issue 5, Pages 475-481Publisher
KOREAN SOC APPLIED PHARMACOLOGY
DOI: 10.4062/biomolther.2016.015
Keywords
Dopamine D-2 receptor; Dopamine D-3 receptor; Dopamine transporter; PICK1; Cell surface expression; Tolerance
Funding
- [KRF- 2014R1A2A2A01002547]
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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 (D3R), which act as autoreceptors to negatively regulate dopaminergic neurons. PICK1 colocalized with both dopamine D-2 receptor (D2R) and D3R in clusters but exerted different functional influences on them. The cell surface expression, agonist affinity, endocytosis, and signaling of D2R were unaffected by the coexpression of PICK1. On the other hand, the surface expression and tolerance of D3R were inhibited by the coexpression of PICK1. These findings show that PICK1 exerts multiple effects on D3R functions.
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