跨越生命王国的水通道蛋白离子通道的基本结构和功能特性。

IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Mohamad Kourghi, Jinxin V Pei, Michael L De Ieso, Saeed Nourmohammadi, Pak Hin Chow, Andrea J Yool
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引用次数: 33

摘要

已知主要内在蛋白(MIP)家族中的水通道蛋白(AQP)通道促进原核生物和真核生物的跨膜水通量。某些类别的aqp还传导离子、甘油、尿素、CO2、一氧化氮和其他小溶质。哺乳动物AQPs 0、1、6、果蝇Big Brain (BIB)、大豆noddulin 26和芥蓝AtPIP2均具有离子通道活性;可能会发现更多的类。新发现的阻滞剂为确定一些AQP双水离子通道的生理作用提供了必要的工具。例如,选择性阻断哺乳动物AQP1中心离子孔的芳基磺酰胺AqB011已被证明会损害HT29结肠癌细胞的迁移。传统草药是选择性AQP1抑制剂的来源,也可以减缓癌细胞的迁移。植物根表皮细胞中表达的AtPIP2;1介导钙离子和质子离子调控的离子电导,为了解环境胁迫反应的分子机制提供了新的思路。晶状体MIP (AQP0)的表达对于维持晶状体的结构、完整性和透明度至关重要,果蝇BIB参与神经源性信号通路,控制果蝇神经母细胞的发育命运;然而,离子通道在MIP和BIB中的作用仍有待明确。需要更广泛的药物组合来研究不同的AQP离子通道原位功能。了解AQPs在水和离子通道中的双重作用,可以为开发新型药物提供信息,以合理干预从农业到人类健康的各种挑战。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Fundamental structural and functional properties of Aquaporin ion channels found across the kingdoms of life.

Aquaporin (AQP) channels in the major intrinsic protein (MIP) family are known to facilitate transmembrane water fluxes in prokaryotes and eukaryotes. Some classes of AQPs also conduct ions, glycerol, urea, CO2 , nitric oxide, and other small solutes. Ion channel activity has been demonstrated for mammalian AQPs 0, 1, 6, Drosophila Big Brain (BIB), soybean nodulin 26, and rockcress AtPIP2;1. More classes are likely to be discovered. Newly identified blockers are providing essential tools for establishing physiological roles of some of the AQP dual water and ion channels. For example, the arylsulfonamide AqB011 which selectively blocks the central ion pore of mammalian AQP1 has been shown to impair migration of HT29 colon cancer cells. Traditional herbal medicines are sources of selective AQP1 inhibitors that also slow cancer cell migration. The finding that plant AtPIP2;1 expressed in root epidermal cells mediates an ion conductance regulated by calcium and protons provided insight into molecular mechanisms of environmental stress responses. Expression of lens MIP (AQP0) is essential for maintaining the structure, integrity and transparency of the lens, and Drosophila BIB contributes to neurogenic signalling pathways to control the developmental fate of fly neuroblast cells; however, the ion channel roles remain to be defined for MIP and BIB. A broader portfolio of pharmacological agents is needed to investigate diverse AQP ion channel functions in situ. Understanding the dual water and ion channel roles of AQPs could inform the development of novel agents for rational interventions in diverse challenges from agriculture to human health.

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来源期刊
Clinical and Experimental Pharmacology and Physiology
Clinical and Experimental Pharmacology and Physiology PHARMACOLOGY & PHARMACY-PHYSIOLOGY
自引率
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发文量
128
期刊介绍: Clinical and Experimental Pharmacology and Physiology is an international journal founded in 1974 by Mike Rand, Austin Doyle, John Coghlan and Paul Korner. Our focus is new frontiers in physiology and pharmacology, emphasizing the translation of basic research to clinical practice. We publish original articles, invited reviews and our exciting, cutting-edge Frontiers-in-Research series’.
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