Structural mechanisms underlying the function of epithelial sodium channel/acid-sensing ion channel.
Structural mechanisms underlying the function of epithelial sodium channel/acid-sensing ion channel.
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DOI：
10.1097/mnh.0b013e328348bcac
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发表时间：
2011-09
影响因子：
3.2
通讯作者：
Carattino MD
中科院分区：
文献类型：
--
作者：
Carattino MD
上皮钠通道/变性蛋白家族包括一组由多种细胞外刺激激活或调节的阳离子选择性离子通道。本文综述了这些发现，提供了新的见解的分子机制，控制这些通道的功能。上皮钠通道促进远端肾单位的Na+重吸收，因此在液体容量稳态和动脉血压调节中起作用。酸敏感离子通道广泛分布在神经系统中，它们在神经系统中参与感觉过程。酸敏感离子通道1的原子结构说明了这些蛋白质的复杂三聚体结构。每个亚基具有两个跨膜跨螺旋，一个高度组织化的胞外域和细胞内N-末端和C-末端。最近的研究结果已经开始阐明的结构元件，使这些通道的感觉和响应细胞外因子。这篇综述强调了细胞外结构域在感知细胞外环境变化中的作用，以及细胞外跨膜结构域界面中的残基在将细胞外变化耦合到通道孔中的作用。上皮细胞钠通道和酸敏感离子通道已经进化为感知细胞外信号。未来的研究应致力于阐明细胞外因子引发的变化如何转化为孔的打开和关闭事件。
The epithelial sodium channel/degenerin family encompasses a group of cation-selective ion channels that are activated or modulated by a variety of extracellular stimuli. This review describes findings that provide new insights into the molecular mechanisms that control the function of these channels. Epithelial sodium channels facilitate Na+ reabsorption in the distal nephron and hence have a role in fluid volume homeostasis and arterial blood pressure regulation. Acid-sensing ion channels are broadly distributed in the nervous system where they contribute to the sensory processes. The atomic structure of acid-sensing ion channel 1 illustrates the complex trimeric architecture of these proteins. Each subunit has two transmembrane spanning helices, a highly organized ectodomain and intracellular N-terminus and C-terminus. Recent findings have begun to elucidate the structural elements that allow these channels to sense and respond to extracellular factors. This review emphasizes the roles of the extracellular domain in sensing changes in the extracellular milieu and of the residues in the extracellular–transmembrane domains interface in coupling extracellular changes to the pore of the channel. Epithelial sodium channels and acid-sensing ion channels have evolved to sense extracellular cues. Future research should be directed toward elucidating how changes triggered by extracellular factors translate into pore opening and closing events.