NCS-1 associates with adenosine A2A receptors and modulates receptor function
NCS-1 associates with adenosine A2A receptors and modulates receptor function
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DOI：
10.3389/fnmol.2012.00053
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发表时间：
2012-01-01
影响因子：
4.8
通讯作者：
Mikhaylova, Marina
中科院分区：
文献类型：
--
作者：
Navarro, Gemma;Hradsky, Johannes;Mikhaylova, Marina
通过细胞内钙浓度的局部变化调节G蛋白偶联受体（GPCR）信号传导是钙调素（CaM）的既定功能，已知钙调素与许多GPCR相互作用。较少被称为密切相关的神经元EF-手Ca 2+传感器蛋白，经常与钙调素的目标与不同的功能结果的功能作用。在本研究中，我们的目的是调查，如果钙调素的目标-A（2A）腺苷受体能够与其他两个神经元钙结合蛋白（nCaBP），即NCS-1和caldendrin。使用生物发光共振能量转移（BRET）和免疫共沉淀实验，我们显示在活细胞中存在A（2A）-NCS-1复合物，而钙调素在测试条件下不与A（2A）受体缔合。有趣的是，NCS-1结合以Ca 2+依赖性方式调节下游A（2A）受体细胞内信号传导。总之，这项研究提供了进一步的证据，神经元钙离子传感器蛋白在GPCR信号的调制中发挥重要作用。
Modulation of G protein-coupled receptor (GPCR) signaling by local changes in intracellular calcium concentration is an established function of Calmodulin (CaM) which is known to interact with many GPCRs. Less is known about the functional role of the closely related neuronal EF-hand Ca2+-sensor proteins that frequently associate with CaM targets with different functional outcome. In the present study we aimed to investigate if a target of CaM-the A(2A) adenosine receptor is able to associate with two other neuronal calcium binding proteins (nCaBPs), namely NCS-1 and caldendrin. Using bioluminescence resonance energy transfer (BRET) and co-immunoprecipitation experiments we show the existence of A(2A)-NCS-1 complexes in living cells whereas caldendrin did not associate with A(2A) receptors under the conditions tested. Interestingly, NCS-1 binding modulated downstream A(2A) receptor intracellular signaling in a Ca2+-dependent manner. Taken together this study provides further evidence that neuronal Ca2+-sensor proteins play an important role in modulation of GPCR signaling.