The association of metabotropic glutamate receptor type 5 with the neuronal Ca2+-binding protein 2 modulates receptor function
The association of metabotropic glutamate receptor type 5 with the neuronal Ca2+-binding protein 2 modulates receptor function
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DOI：
10.1111/j.1471-4159.2009.06348.x
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发表时间：
2009-10-01
影响因子：
4.7
通讯作者：
Ciruela, Francisco
中科院分区：
文献类型：
--
作者：
Canela, Laia;Fernandez-Duenas, Victor;Ciruela, Francisco
代谢型谷氨酸 (mGlu) 受体部分介导谷氨酸的中枢神经系统作用。这些受体与大量细胞内蛋白质相互作用，最终作用是调节受体功能。在这里，使用免疫共沉淀和下拉实验，我们在转染的人胚胎肾细胞和大鼠海马中显示了 mGlu(5) 受体和 NECAB2 之间密切且特异性的相互作用。有趣的是，在下拉实验中，钙浓度的增加大大降低了这两种蛋白质相互作用的能力，表明NECAB2以钙调节方式与mGlu(5)受体结合。免疫电镜检测大鼠海马结构中的NECAB2和mGlu(5)受体表明这两种蛋白共同分布在锥体细胞的同一亚细胞区室中。此外，NECAB2/mGlu(5) 受体相互作用调节 mGlu(5b) 介导的磷酸肌醇积累和细胞外信号调节激酶/丝裂原激活蛋白激酶途径的激活。总体而言，这些发现表明 NECAB2 通过与 mGlu(5b) 受体的物理相互作用来调节受体功能。
Metabotropic glutamate (mGlu) receptors mediate in part the CNS effects of glutamate. These receptors interact with a large array of intracellular proteins in which the final role is to regulate receptor function. Here, using co-immunoprecipitation and pull-down experiments we showed a close and specific interaction between mGlu(5) receptor and NECAB2 in both transfected human embryonic kidney cells and rat hippocampus. Interestingly, in pull-down experiments increasing concentrations of calcium drastically reduced the ability of these two proteins to interact, suggesting that NECAB2 binds to mGlu(5) receptor in a calcium-regulated manner. Immunoelectron microscopy detection of NECAB2 and mGlu(5) receptor in the rat hippocampal formation indicated that both proteins are codistributed in the same subcellular compartment of pyramidal cells. In addition, the NECAB2/mGlu(5) receptor interaction regulated mGlu(5b)-mediated activation of both inositol phosphate accumulation and the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway. Overall, these findings indicate that NECAB2 by its physical interaction with mGlu(5b) receptor modulates receptor function.