GIPC recruits GAIP (RGS19) to attenuate dopamine D2 receptor signaling.
Pleiotropic G proteins are essential for the action of hormones and neurotransmitters and are activated by stimulation of G protein-coupled receptors (GPCR), which initiates heterotrimer dissociation of the G protein, exchange of GDP for GTP on its Galpha subunit and activation of effector proteins. Regulator of G protein signaling (RGS) proteins regulate this cascade and can be recruited to the membrane upon GPCR activation. Direct functional interaction between RGS and GPCR has been hypothesized. We show that recruitment of GAIP (RGS19) by the dopamine D2 receptor (D2R), a GPCR, required the scaffold protein GIPC (GAIP-interacting protein, C terminus) and that all three were coexpressed in neurons and neuroendocrine cells. Dynamic translocation of GAIP to the plasma membrane and coassembly in a protein complex in which GIPC was a required component was dictated by D2R activation and physical interactions. In addition, two different D2R-mediated responses were regulated by the GTPase activity of GAIP at the level of the G protein coupling in a GIPC-dependent manner. Since GIPC exclusively interacted with GAIP and selectively with subsets of GPCR, this mechanism may serve to sort GPCR signaling in cells that usually express a large repertoire of GPCRs, G proteins, and RGS.
Jeanneteau
Freddy
F
Unité de Neurobiologie et Pharmacologie Moléculaire, Institut National de la Santé et de la Recherche Médicale, U 573, Centre Paul Broca, 75104 Paris, France. jeannet@broca.inserm.fr
Guillin
Olivier
O
Diaz
Jorge
J
Griffon
Nathalie
N
Sokoloff
Pierre
P
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D016466:CHO Cells; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D020710:RGS Proteins / Q000378:metabolism; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C492009:GIPC1 protein, human; D009479:Neuropeptides; D016376:Oligonucleotides, Antisense; D010750:Phosphoproteins; D020710:RGS Proteins; D017448:Receptors, Dopamine D2; C097187:regulator of G-protein signalling 19; D049452:Green Fluorescent Proteins; D016718:Arachidonic Acid; D000242:Cyclic AMP; D005982:Glutathione Transferase