Neuronal expression of soluble adenylyl cyclase in the mammalian brain.

Neuronal expression of soluble adenylyl cyclase in the mammalian brain.
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DOI:
10.1016/j.brainres.2013.04.027
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发表时间:
2013-06-26
期刊:
影响因子:
2.9
通讯作者:
Levin LR
Levin LR
中科院分区:
医学3区
文献类型:
--
作者:
Chen J;Martinez J;Milner TA;Buck J;Levin LR

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环磷酸腺苷(cAMP)是一种重要的、普遍存在的第二信使,参与多种信号转导途径。可溶性腺苷酸环化酶(Soluble adenylyl cyclase,sAC)是一种新的cAMP来源,具有独特的定位和调控机制。它最初是在哺乳动物睾丸中发现的,并被碳酸氢盐和钙激活。sAC参与多种过程,包括星形胶质细胞-神经元代谢偶联和神经元轴突生长。然而,尽管有这些功能研究,sAC蛋白在睾丸外表达的证明一直存在争议。最近,我们发现sAC在星形胶质细胞的免疫反应,但sAC的神经元表达的问题仍然存在。我们现在描述了第二代sAC基因敲除小鼠模型(C2 KO),旨在更明确地解决sAC表达的问题,我们最终证明使用免疫电子显微镜,sAC在中枢神经系统的神经元中表达。
Cyclic 3’, 5’-adenosine monophosphate (cAMP) is a critical and ubiquitous second messenger involved in a multitude of signaling pathways. Soluble adenylyl cyclase (sAC) is a novel source of cAMP subject to unique localization and regulation. It was originally discovered in mammalian testis and found to be activated by bicarbonate and calcium. sAC has been implicated in diverse processes, including astrocyte-neuron metabolic coupling and axonal outgrowth of neurons. However, despite these functional studies, demonstration of sAC protein expression outside of testis has been controversial. Recently, we showed sAC immunoreactivity in astrocytes, but the question of neuronal expression of sAC remained. We now describe the generation of a second sAC knockout mouse model (C2KO) designed to more definitively address questions of sAC expression, and we demonstrate conclusively using immune-electron microscopy that sAC is expressed in neuronal profiles in the central nervous system.
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