Evidence that calmodulin binding to the dopamine D2 receptor enhances receptor signaling

Yong Liu, David C. Buck, Tara A. MacEy, Hongxiang Lan, Kim Neve

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The Ca2+ sensor calmodulin (CaM) regulates numerous proteins involved in G protein-coupled receptor (GPCR) signaling. CaM binds directly to some GPCRs, including the dopamine D2 receptor. We confirmed that the third intracellular loop of the D2 receptor is a direct contact point for CaM binding using coimmunoprecipitation and a polyHis pull-down assay, and we determined that the D2-like receptor agonist 7-OH-DPAT increased the colocalization of the D2 receptor and endogenous CaM in both 293 cells and in primary neostriatal cultures. The N-terminal three or four residues of D2-IC3 were required for the binding of CaM; mutation of three of these residues in the full-length receptor (I210C/K211C/I212C) decreased the coprecipitation of the D2 receptor and CaM and also significantly decreased D2 receptor signaling, without altering the coupling of the receptor to G proteins. Taken together, these findings suggest that binding of CaM to the dopamine D2 receptor enhances D2 receptor signaling.

Original languageEnglish (US)
Pages (from-to)47-65
Number of pages19
JournalJournal of Receptors and Signal Transduction
Volume27
Issue number1
DOIs
StatePublished - Jan 2007

Fingerprint

Dopamine D2 Receptors
Calmodulin
Point contacts
Coprecipitation
G-Protein-Coupled Receptors
GTP-Binding Proteins
Assays
Mutation
Sensors

Keywords

  • Adenylate cyclase
  • Calmodulin
  • D2 Receptor
  • Mitogen-activated protein kinase
  • Protein:protein interaction
  • Receptor signaling

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Evidence that calmodulin binding to the dopamine D2 receptor enhances receptor signaling. / Liu, Yong; Buck, David C.; MacEy, Tara A.; Lan, Hongxiang; Neve, Kim.

In: Journal of Receptors and Signal Transduction, Vol. 27, No. 1, 01.2007, p. 47-65.

Research output: Contribution to journalArticle

Liu, Yong ; Buck, David C. ; MacEy, Tara A. ; Lan, Hongxiang ; Neve, Kim. / Evidence that calmodulin binding to the dopamine D2 receptor enhances receptor signaling. In: Journal of Receptors and Signal Transduction. 2007 ; Vol. 27, No. 1. pp. 47-65.
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