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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.
Pubmed: (View Article at PubMed) PMID:14617818
DOI: Full-text: DOI:10.1091/mbc.E03-05-0293

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.

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CRRD Object Information
CRRD ID: 1581465
Created: 2006-10-04
Species: All species
Last Modified: 2006-10-04
Status: ACTIVE



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