Evidence that calmodulin binding to the dopamine D2 receptor enhances receptor signaling
Evidence that calmodulin binding to the dopamine D2 receptor enhances receptor signaling
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DOI：
10.1080/10799890601094152
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发表时间：
2007-01-01
影响因子：
2.8
通讯作者：
Neve, Kim A.
中科院分区：
文献类型：
--
作者：
Liu, Yong;Buck, David C.;Neve, Kim A.
钙离子感受器钙调素(CaM)调节大量参与G蛋白偶联受体(GPCR)信号转导的蛋白质。CaM直接与一些GPCRs结合，包括多巴胺D-2受体。我们用免疫共沉淀和PolyHis下拉实验证实了D-2受体的第三个细胞内环是CaM结合的直接接触点，并且我们确定D-2样受体激动剂7-OH-DPAT增加了D-2受体和内源性CaM在293细胞和原代新纹状体培养中的共存。D-2-IC3的N端3个或4个残基是与CaM结合所必需的，全长受体(I210C/K211C/I212C)中的3个残基的突变减少了D-2受体和CaM的共沉淀，并显著减少了D-2受体信号转导，但不改变受体与G蛋白的偶联。综上所述，这些发现表明CaM与多巴胺D-2受体的结合增强了D-2受体的信号转导。
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 D-2 receptor. We confirmed that the third intracellular loop of the D-2 receptor is a direct contact point for CaM binding using coimmunoprecipitation and a polyHis pulldown assay, and we determined that the D-2-like receptor agonist 7-OH-DPAT increased the colocalization of the D-2 receptor and endogenous CaM in both 293 cells and in primary neostriatal cultures. The N-terminal three or four residues of D-2-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 D-2 receptor and CaM and also significantly decreased D-2 receptor signaling, without altering the coupling of the receptor to G proteins. Taken together, these findings suggest that binding of CaM to the dopamine D-2 receptor enhances D-2 receptor signaling.