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 language | English (US) |
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Pages (from-to) | 47-65 |
Number of pages | 19 |
Journal | Journal of Receptors and Signal Transduction |
Volume | 27 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2007 |
Keywords
- Adenylate cyclase
- Calmodulin
- D2 Receptor
- Mitogen-activated protein kinase
- Protein:protein interaction
- Receptor signaling
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology