Search Organism: All OrganismsArabidopsis thalianaBacillus subtilis 168Bos taurusCaenorhabditis elegansCanis familiarisDanio rerioDrosophila melanogasterEquus caballusEscherichia coli K12Gallus gallusHomo sapiensMacaca mulattaMus musculusNematostella vectensisOryza sativaPan troglodytesRattus norvegicusSaccharomyces cerevisiaeSchizosaccharomyces pombeStrongylocentrotus purpuratusTakifugu rubripesXenopus laevis home help / support contribute downloads mirrors about us J. Neurosci. Oct (2002); 22(19):8476-86 Interaction with neuronal calcium sensor NCS-1 mediates desensitization of the D2 dopamine receptor. Kabbani N, Negyessy L, Lin R, Goldman-Rakic P, Levenson R Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania 17033, USA. Abstract: Dopaminergic transmission within limbic regions of the brain is highly dependent on the regulation of D2 receptor activity. Here we show that the neuronal calcium sensor-1 (NCS-1) can mediate desensitization of D2 dopamine receptors. Analysis of D2 receptors expressed in human embryonic kidney 293 cells indicates that NCS-1 attenuates agonist-induced receptor internalization via a mechanism that involves a reduction in D2 receptor phosphorylation. This effect of NCS-1 was accompanied by an increase in D2 receptor-mediated cAMP inhibition after dopamine stimulation. The ability of NCS-1 to modulate D2 receptor signaling was abolished after a single amino acid mutation in NCS-1 that has been shown to impair the calcium-binding properties of NCS-1. Coimmunoprecipitation experiments from striatal neurons reveal that NCS-1 is found in association with both the D2 receptor and G-protein-coupled receptor kinase 2, a regulator of D2 receptor desensitization. Colocalization of NCS-1 and D2 receptors was examined in both primate and rodent brain. In striatum, NCS-1 and D2 receptors were found to colocalize within sites of synaptic transmission and in close proximity to intracellular calcium stores. NCS-1-D2 receptor interaction may serve to couple dopamine and calcium signaling pathways, thereby providing a critical component in the regulation of dopaminergic signaling in normal and diseased brain. [PUBMED: 12351722] Copyright © 2009, Tyers Lab, The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, All Rights Reserved. terms and conditions - privacy policy - Osprey Network Visualization System BioGRID: A General Repository for Interaction Datasets. Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers. Nucleic Acids Res. Jan 1;34:D535-9.