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

Nadine Kabbani, Laszlo Negyessy, Ridwan Lin, Patricia Goldman-Rakic, Robert Levenson

Research output: Contribution to journalArticlepeer-review

192 Scopus citations


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 calciumbinding 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.

Original languageEnglish (US)
Pages (from-to)8476-8486
Number of pages11
JournalJournal of Neuroscience
Issue number19
StatePublished - Oct 1 2002

All Science Journal Classification (ASJC) codes

  • General Neuroscience


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