Water channels and barriers formed by claudins
Water channels and barriers formed by claudins
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DOI：
10.1111/nyas.13383
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发表时间：
2017-06
影响因子：
5.2
通讯作者：
R. Rosenthal;D. Günzel;Dian Theune;Carolina Czichos;J. Schulzke;M. Fromm
中科院分区：
文献类型：
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作者：
R. Rosenthal;D. Günzel;Dian Theune;Carolina Czichos;J. Schulzke;M. Fromm
在渗漏的上皮细胞，如肾近端小管和小肠的生理学研究，已经记录了水通过跨细胞和细胞旁途径的运输。水通道蛋白的发现为水跨细胞运动提供了分子基础。相比之下，一个特定的细胞旁水通路的贡献，甚至存在，已经有很长一段时间的争议，直到阳离子通道形成紧密连接蛋白claudin-2被证明也允许水通过其孔的细胞旁通道。在近端肾小管中，基于claudin-2的水转运占总水转运的23-30%。其他细胞旁离子通道（claudin-10a，-10 b和-17）被证明是不透水的，尽管它们的孔径足以让水分子通过。对形成屏障的claudin（如claudin-1和claudin-3）的研究表明，这些密封性claudin的表达变化不会影响跨上皮水渗透性，claudin-1和claudin-3收紧了细胞旁通路，对抗离子和较大的溶质。目前的遗传、分子、计算和生理研究才刚刚开始探索细胞旁渗透的机制和调节。
Physiological studies in leaky epithelia, like kidney proximal tubules and the small intestine, have documented water transport via both transcellular and paracellular pathways. The discovery of aquaporin water channels provided a molecular basis for transcellular water movement. In contrast, the contribution, or even existence, of a specific paracellular water pathway has been disputed for a long time, until the cation channel–forming tight junction protein claudin‐2 was shown to also permit the paracellular passage of water through its pore. In proximal kidney tubules, claudin‐2–based water transport contributes 23–30% of the total water transport. Other paracellular ion channels (claudin‐10a, ‐10b, and ‐17) proved to be impermeable to water, although their pore size would be sufficient for water molecules to pass. Studies of barrier‐forming claudins, like claudin‐1 and claudin‐3, which tighten the paracellular pathway against ions and larger solutes, indicate that changes in the expression of these sealing claudins do not influence transepithelial water permeability. The present genetic, molecular, computational, and physiological studies are just now beginning to probe the mechanisms and regulation of paracellular permeation.