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PMID:22843680

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Citation

Ha, CM, Park, D, Han, JK, Jang, JI, Park, JY, Hwang, EM, Seok, H and Chang, S (2012) Calcyon forms a novel ternary complex with dopamine D1 receptor through PSD-95 protein and plays a role in dopamine receptor internalization. J. Biol. Chem. 287:31813-22

Abstract

Calcyon, once known for interacting directly with the dopamine D(1) receptor (D(1)DR), is implicated in various neuropsychiatric disorders including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. Although its direct interaction with D(1)DR has been shown to be misinterpreted, it still plays important roles in D(1)DR signaling. Here, we found that calcyon interacts with the PSD-95 and subsequently forms a ternary complex with D(1)DR through PSD-95. Calcyon is phosphorylated on Ser-169 by the PKC activator phorbol 12-myristate 13-acetate or by the D(1)DR agonist SKF-81297, and its phosphorylation increases its association with PSD-95 and recruitment to the cell surface. Interestingly, the internalization of D(1)DR at the cell surface was enhanced by phorbol 12-myristate 13-acetate and SKF-81297 in the presence of calcyon, but not in the presence of its S169A phospho-deficient mutant, suggesting that the phosphorylation of calcyon and the internalization of the surface D(1)DR are tightly correlated. Our results suggest that calcyon regulates D(1)DR trafficking by forming a ternary complex with D(1)DR through PSD-95 and thus possibly linking glutamatergic and dopamine receptor signalings. This also raises the possibility that a novel ternary complex could represent a potential therapeutic target for the modulation of related neuropsychiatric disorders.

Links

PubMed PMC3442515 Online version:10.1074/jbc.M112.370601

Keywords

Animals; Brain/metabolism; Endocytosis; Gene Library; HEK293 Cells; Humans; Intracellular Signaling Peptides and Proteins/chemistry; Membrane Proteins/chemistry; Models, Neurological; Neurons/metabolism; Phosphorylation; Protein Binding; Rats; Receptors, Dopamine/chemistry; Receptors, Dopamine D1/chemistry; Signal Transduction

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:CALY

enables

GO:0044877: protein-containing complex binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:2518
RGD:68424

F

Seeded From UniProt

complete

RAT:DLG4

enables

GO:0044877: protein-containing complex binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:2518
RGD:621719

F

Seeded From UniProt

complete

RAT:DRD1

enables

GO:0044877: protein-containing complex binding

ECO:0000353: physical interaction evidence used in manual assertion

RGD:621719
RGD:68424

F

Seeded From UniProt

complete

Notes

See also

References

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