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

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

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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
Issue number1
StatePublished - Jan 2007


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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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