Dexras1: A G protein specifically coupled to neuronal nitric oxide synthase via CAPON
Dexras1: A G protein specifically coupled to neuronal nitric oxide synthase via CAPON
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DOI：
10.1016/s0896-6273(00)00095-7
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发表时间：
2000-10-01
期刊：
影响因子：
16.2
通讯作者：
Snyder, SH
中科院分区：
文献类型：
--
作者：
Fang, M;Jaffrey, SR;Snyder, SH
由于一氧化氮（NO）是一种高度反应性的信号分子，通过与氧，超氧化物和谷胱甘肽反应的化学失活与靶蛋白的特异性相互作用竞争。连接神经元NO合酶（nNOS）与特定靶蛋白的接头蛋白可增强NO信号传导。在这里，我们确定了一个选择性的相互作用的nNOS衔接蛋白CAPON与Dexras 1，大脑丰富的小单体G蛋白的Pas家族的成员。我们发现，Dexras 1被激活的NO供体以及NMDA受体刺激的皮质神经元中的NO合成。Dexras 1作为nNOS生理靶点的重要性是通过选择性降低Dexras 1活化而不是H-Ras或其他四种Pas家族成员来确定的，在具有nNOS靶向基因组缺失（nNOS（-/-））的小鼠脑中。我们还发现，nNOS，CAPON，和Dexras 1形成一个三元复合物，增强了nNOS激活Dexras 1的能力。这些发现将Dexras 1鉴定为一种新的生理性NO效应子，并表明nNOS锚定到特定靶点是NO信号传导增强的机制。
Because nitric oxide (NO) is a highly reactive signaling molecule, chemical inactivation by reaction with oxygen, superoxide, and glutathione competes with specific interactions with target proteins. NO signaling may be enhanced by adaptor proteins that couple neuronal NO synthase (nNOS) to specific target proteins. Here we identify a selective interaction of the nNOS adaptor protein CAPON with Dexras1, a brain-enriched member of the Pas family of small monomeric G proteins. We find that Dexras1 is activated by NO donors as well as by NMDA receptor-stimulated NO synthesis in cortical neurons. The importance of Dexras1 as a physiologic target of nNOS is established by the selective decrease of Dexras1 activation, but not H-Ras or four other Pas family members, in the brains of mice harboring a targeted genomic deletion of nNOS (nNOS(-/-)). We also find that nNOS, CAPON, and Dexras1 form a ternary complex that enhances the ability of nNOS to activate Dexras1. These findings identity Dexras1 as a novel physiologic NO effector and suggest that anchoring of nNOS to specific targets is a mechanism by which NO signaling is enhanced.