Major occurrence of the new α2β1 isoform of NO-sensitive guanylyl cyclase in brain
Major occurrence of the new α2β1 isoform of NO-sensitive guanylyl cyclase in brain
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DOI：
10.1016/s0898-6568(02)00078-5
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发表时间：
2003-02-01
影响因子：
4.8
通讯作者：
Koesling, D
中科院分区：
文献类型：
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作者：
Mergia, E;Russwurm, M;Koesling, D
NO敏感的鸟苷酸环化酶(GC)是NO的效应分子，在NO/cGMP信号转导通路中起着关键作用。除了已知的GC亚型(α(1)β(1))外，最近还发现另一种异二聚体(α(2)β(1))与脑中的PSD-95有关。在这里，我们报告了所有已知的鸟苷酸环化酶亚基的组织分布，以阐明异构体在小鼠不同组织中的含量。用实时定量聚合酶链式反应检测鸟苷酸环化酶亚单位的水平，最重要的结果在Western blotts中得到验证。我们证明了α(2)β(1)异二聚体主要存在于脑中，在肺中发现了大量的异源二聚体，在所有其他被测试的组织中发现了较少的量。在大脑中，α(2)β(1)和α(1)β(1)亚型的水平是相似的；在所有其他组织中，α(1)β(1)异二聚体是主要的亚型。在肺中发现了最高的鸟苷酸环化酶含量；这里的GC大约是脑中的两倍。综上所述，α(2)β(1)异二聚体的主要存在表明在突触传递中具有特殊的作用；这种异构体是否也存在于脑外的神经元网络中有待于未来的研究。(C)2003 Elsevier Science Inc.保留所有权利。
NO-sensitive guanylyl cyclase (GC) acts as the effector molecule for NO and therefore plays a key role in the NO/cGMP signalling cascade. Besides the long known GC isoform (alpha(1)beta(1)), another heterodimer (alpha(2)beta(1)) has recently been identified to be associated with PSD-95 in brain.Here, we report on the tissue distribution of all known guanylyl cyclase subunits to elucidate the isoform content in different tissues of the mouse. The guanylyl cyclase subunit levels were assessed with quantitative real-time PCR, and the most important results were verified in Western blots. We demonstrate the major occurrence of the alpha(2)beta(1) heterodimer in brain, find a significant amount in lung and lower amounts in all other tissues tested. In brain, the levels of the alpha(2)beta(1) and alpha(1)beta(1) isoforms were comparable; in all other tissues, the alpha(1)beta(1) heterodimer was the predominating isoform. The highest guanylyl cyclase content was found in lung; here the GC amounted to approximately twice as much as in brain.In sum, the major occurrence of the alpha(2)beta(1) heterodimer suggests a special role in synaptic transmission; whether this isoform outside the brain also occurs in neuronal networks has to be addressed in future studies. (C) 2003 Elsevier Science Inc. All rights reserved.