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水通道蛋白双水和离子通道的结构、功能及转化相关性。

Structure, function and translational relevance of aquaporin dual water and ion channels.

机构信息

School of Medical Sciences and The Adelaide Centre for Neuroscience Research, Medical School South, Frome Road, University of Adelaide, Adelaide, SA 5005, Australia.

出版信息

Mol Aspects Med. 2012 Oct-Dec;33(5-6):553-61. doi: 10.1016/j.mam.2012.02.001. Epub 2012 Feb 11.

DOI:10.1016/j.mam.2012.02.001
PMID:22342689
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3419283/
Abstract

Aquaporins have been assumed to be selective for water alone, and aquaglyceroporins are accepted as carrying water and small uncharged solutes including glycerol. This review presents an expanded view of aquaporins as channels with more complex mechanisms of regulation and diverse repertoires of substrate permeabilities than were originally appreciated in the early establishment of the field. The role of aquaporins as dual water and gated ion channels is likely to have physiological and potentially translational relevance, and can be evaluated with newly developed molecular and pharmacological tools. Ion channel activity has been shown for Aquaporins -0, -1, and -6, Drosphila Big Brain, and plant Nodulin-26. Although the concept of ion channel function in aquaporins remains controversial, research advances are beginning to define not only the ion channel function but also the detailed molecular mechanisms that govern and mediate the multifunctional capabilities. With regard to physiological relevance, the adaptive benefit of expression of ion channel activity in aquaporins, implied by amino acid sequence conservation of the ion channel gating domains, suggests they provide more than water or glycerol and solute transport. Dual ion and water channels are of interest for understanding the modulation of transmembrane fluid gradients, volume regulation, and possible signal transduction in tissues expressing classes of aquaporins that have the dual function capability. Other aquaporin classes might be found in future work to have ion channel activities, pending identification of the possible signaling pathways that could govern activation.

摘要

水通道蛋白被认为只对水具有选择性,水甘油通道蛋白被认为可携带水和包括甘油在内的小不带电荷溶质。本综述提出了一个扩展的观点,即水通道蛋白作为通道具有更复杂的调节机制和更多样的底物通透性谱,这超出了该领域早期建立时的最初认识。水通道蛋白作为双重水和门控离子通道的作用可能具有生理和潜在的转化意义,可以用新开发的分子和药理学工具进行评估。已经证明 Aquaporins -0、-1 和 -6、果蝇 Big Brain 和植物 Nodulin-26 具有离子通道活性。尽管离子通道功能在水通道蛋白中的概念仍然存在争议,但研究进展开始不仅定义了离子通道功能,还定义了控制和介导多功能能力的详细分子机制。就生理相关性而言,离子通道门控域氨基酸序列保守性所暗示的离子通道活性在水通道蛋白中的表达适应性益处表明,它们提供的功能不仅仅是水或甘油和溶质运输。双重离子和水通道对于理解表达具有双重功能能力的水通道蛋白类别的组织中跨膜流体梯度的调节、体积调节和可能的信号转导很重要。在可能控制激活的信号通路被确定之前,其他水通道蛋白类可能会在未来的工作中被发现具有离子通道活性。

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