Molecular cloning and characterization of a calmodulin-dependent phosphodiesterase enriched in olfactory sensory neurons.

Molecular cloning and characterization of a calmodulin-dependent phosphodiesterase enriched in olfactory sensory neurons.
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DOI:
10.1073/pnas.92.21.9677
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发表时间:
1995-10
影响因子:
11.1
通讯作者:
Chen Yan;A. Zhao;J. Bentley;Kate LOUGHNEYt;Ken FERGUSONt;J. Beavo
Chen Yan;A. Zhao;J. Bentley;Kate LOUGHNEYt;Ken FERGUSONt;J. Beavo
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Chen Yan;A. Zhao;J. Bentley;Kate LOUGHNEYt;Ken FERGUSONt;J. Beavo

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动物对气味的感知必须是一个快速但短暂的过程,需要即时响应并快速终止信号。先前的生化和电生理学研究表明,一种或多种磷酸二酯酶 (PDE) 可能在气味剂诱导的 cAMP 信号的快速终止中发挥重要作用。在这里,我们报告了来自大鼠嗅上皮的 cDNA 的分子克隆、表达和表征,该 cDNA 编码钙调蛋白依赖性 PDE 家族成员(称为 PDE1C)。该酶对 cAMP 和 cGMP 表现出高亲和力,对 cAMP 的 Km 远低于任何其他神经元 Ca2+/钙调蛋白依赖性 PDE。编码这种酶的 mRNA 在嗅觉上皮细胞中高度富集,并且在其他六种测试组织中未检测到。然而,RNase 保护分析表明,与该酶相关的其他选择性剪接变体在其他几种组织中也有表达。在嗅觉上皮内,这种酶似乎只在感觉神经元中表达。这种Ca2+/钙调蛋白依赖性PDE对cAMP的高亲和力以及其mRNA高度集中在嗅觉感觉神经元中的事实表明它在Ca(2+)调节的嗅觉信号终止中发挥重要作用。
The sensing of an odorant by an animal must be a rapid but transient process, requiring an instant response and also a speedy termination of the signal. Previous biochemical and electrophysiological studies suggest that one or more phosphodiesterases (PDEs) may play an essential role in the rapid termination of the odorant-induced cAMP signal. Here we report the molecular cloning, expression, and characterization of a cDNA from rat olfactory epithelium that encodes a member of the calmodulin-dependent PDE family designated as PDE1C. This enzyme shows high affinity for cAMP and cGMP, having a Km for cAMP much lower than that of any other neuronal Ca2+/calmodulin-dependent PDE. The mRNA encoding this enzyme is highly enriched in olfactory epithelium and is not detected in six other tissues tested. However, RNase protection analyses indicate that other alternative splice variants related to this enzyme are expressed in several other tissues. Within the olfactory epithelium, this enzyme appears to be expressed exclusively in the sensory neurons. The high affinity for cAMP of this Ca2+/calmodulin-dependent PDE and the fact that its mRNA is highly concentrated in olfactory sensory neurons suggest an important role for it in a Ca(2+)-regulated olfactory signal termination.