RGD Reference Report - Interaction with neuronal calcium sensor NCS-1 mediates desensitization of the D2 dopamine receptor. - Rat Genome Database

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Interaction with neuronal calcium sensor NCS-1 mediates desensitization of the D2 dopamine receptor.

Authors: Kabbani, Nadine  Negyessy, Laszlo  Lin, Ridwan  Goldman-Rakic, Patricia  Levenson, Robert 
Citation: Kabbani N, etal., J Neurosci. 2002 Oct 1;22(19):8476-86.
RGD ID: 13702158
Pubmed: PMID:12351722   (View Abstract at PubMed)
PMCID: PMC6757796   (View Article at PubMed Central)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
postsynapse is_active_inIDA 13702158PMID:12351722SynGO 

Objects Annotated

Genes (Rattus norvegicus)
Ncs1  (neuronal calcium sensor 1)


Additional Information