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

Nadine Kabbani, L. Négyessy, Ridwan Lin, Patricia Goldman-Rakic, Robert Levenson

Research output: Contribution to journalArticle

170 Citations (Scopus)

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 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
Pages (from-to)8476-8486
Number of pages11
JournalJournal of Neuroscience
Volume22
Issue number19
Publication statusPublished - Oct 1 2002

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Dopamine D2 Receptors
Calcium
Dopamine
G-Protein-Coupled Receptor Kinase 2
frequenin calcium sensor proteins
Cyclic AMP Receptors
Corpus Striatum
Calcium Signaling
Brain
Brain Diseases
Synaptic Transmission
Primates
Rodentia
Phosphorylation
Kidney
Neurons
Amino Acids
Mutation

Keywords

  • Calcium signaling
  • Desensitization
  • Dopamine receptor
  • Frequenin
  • GPCR
  • GRK
  • Neuronal calcium sensor-1
  • Yeast two-hybrid

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Interaction with neuronal calcium sensor NCS-1 mediates desensitization of the D2 dopamine receptor. / Kabbani, Nadine; Négyessy, L.; Lin, Ridwan; Goldman-Rakic, Patricia; Levenson, Robert.

In: Journal of Neuroscience, Vol. 22, No. 19, 01.10.2002, p. 8476-8486.

Research output: Contribution to journalArticle

Kabbani, N, Négyessy, L, Lin, R, Goldman-Rakic, P & Levenson, R 2002, 'Interaction with neuronal calcium sensor NCS-1 mediates desensitization of the D2 dopamine receptor', Journal of Neuroscience, vol. 22, no. 19, pp. 8476-8486.
Kabbani, Nadine ; Négyessy, L. ; Lin, Ridwan ; Goldman-Rakic, Patricia ; Levenson, Robert. / Interaction with neuronal calcium sensor NCS-1 mediates desensitization of the D2 dopamine receptor. In: Journal of Neuroscience. 2002 ; Vol. 22, No. 19. pp. 8476-8486.
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