RGD Reference Report - Interactions of GIPC with dopamine D2, D3 but not D4 receptors define a novel mode of regulation of G protein-coupled receptors. - Rat Genome Database

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Interactions of GIPC with dopamine D2, D3 but not D4 receptors define a novel mode of regulation of G protein-coupled receptors.

Authors: Jeanneteau, F  Diaz, J  Sokoloff, P  Griffon, N 
Citation: Jeanneteau F, etal., Mol Biol Cell. 2004 Feb;15(2):696-705. Epub 2003 Nov 14.
RGD ID: 1581465
Pubmed: PMID:14617818   (View Abstract at PubMed)
PMCID: PMC329290   (View Article at PubMed Central)
DOI: DOI:10.1091/mbc.E03-05-0293   (Journal Full-text)

The C-terminus domain of G protein-coupled receptors confers a functional cytoplasmic interface involved in protein association. By screening a rat brain cDNA library using the yeast two-hybrid system with the C-terminus domain of the dopamine D(3) receptor (D(3)R) as bait, we characterized a new interaction with the PDZ domain-containing protein, GIPC (GAIP interacting protein, C terminus). This interaction was specific for the dopamine D(2) receptor (D(2)R) and D(3)R, but not for the dopamine D(4) receptor (D(4)R) subtype. Pull-down and affinity chromatography assays confirmed this interaction with recombinant and endogenous proteins. Both GIPC mRNA and protein are widely expressed in rat brain and together with the D(3)R in neurons of the islands of Calleja at plasma membranes and in vesicles. GIPC reduced D(3)R signaling, cointernalized with D(2)R and D(3)R, and sequestered receptors in sorting vesicles to prevent their lysosomal degradation. Through its dimerization, GIPC acts as a selective scaffold protein to assist receptor functions. Our results suggest a novel function for GIPC in the maintenance, trafficking, and signaling of GPCRs.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
G protein-coupled receptor internalization  IDA 1581465; 1581465 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
endocytic vesicle  IDA 1581465; 1581465; 1581465 RGD 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Drd2  (dopamine receptor D2)
Drd3  (dopamine receptor D3)
Gipc1  (GIPC PDZ domain containing family, member 1)


Additional Information