Identification and experimental verification of a novel family of bacterial cyclic nucleotide-gated (bCNG) ion channels
Identification and experimental verification of a novel family of bacterial cyclic nucleotide-gated (bCNG) ion channels
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DOI：
10.1016/j.bbamem.2010.06.001
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发表时间：
2010-09-01
影响因子：
3.4
通讯作者：
Maurer, Joshua A.
中科院分区：
文献类型：
--
作者：
Caldwell, David B.;Malcolm, Hannah R.;Maurer, Joshua A.
对细菌离子通道的研究为机械敏感性和电压门控性离子通道的结构-功能关系提供了重要的见解。然而，到目前为止，很少有响应小分子的细菌通道被鉴定、克隆和表征。在这里，我们使用生物信息学，以确定一个新的家庭的细菌环核苷酸门控（bCNG）离子通道包含一个通道结构域相关的序列同源性的机械敏感通道的小电导（MSCS）。在这份初步报告中，我们克隆了这个通道家族的选定成员，使用电生理学测量来验证它们直接门控响应环核苷酸的能力，并使用渗透压下休克来证明它们缺乏机械敏感性。除了提供对细菌生理学的深入了解外，这些通道还将为研究人员提供一个有用的模型系统，以研究配体门控离子通道（LGIC）在高等生物信号传导过程中的作用。这些通道的鉴定为LGIC的结构和功能研究提供了基础，这在哺乳动物通道上是难以进行的。此外，bCNG通道的发现意味着细菌具有环核苷酸门控和环核苷酸调节的离子通道，其类似于参与真核生物第二信使信号通路的离子通道。(C)2010年爱思唯尔。All rights reserved.
Studies of bacterial ion channels have provided significant insights into the structure-function relationships of mechanosensitive and voltage-gated ion channels. However, to date, very few bacterial channels that respond to small molecules have been identified, cloned, and characterized. Here, we use bioinformatics to identify a novel family of bacterial cyclic nucleotide-gated (bCNG) ion channels containing a channel domain related by sequence homology to the mechanosensitive channel of small conductance (MscS). In this initial report, we clone selected members of this channel family, use electrophysiological measurements to verify their ability to directly gate in response to cyclic nucleotides, and use osmotic downshock to demonstrate their lack of mechanosensitivity. In addition to providing insight into bacterial physiology, these channels will provide researchers with a useful model system to investigate the role of ligand-gated ion channels (LGICs) in the signaling processes of higher organisms. The identification of these channels provides a foundation for structural and functional studies of LGICs that would be difficult to perform on mammalian channels. Moreover, the discovery of bCNG channels implies that bacteria have cyclic nucleotide-gated and cyclic nucleotide-modulated ion channels, which are analogous to the ion channels involved in eukaryotic secondary messenger signaling pathways. (C) 2010 Elsevier By. All rights reserved.