Verkman A S, van Hoek A N, Ma T, Frigeri A, Skach W R, Mitra A, Tamarappoo B K, Farinas J
Department of Medicine, University of California, San Francisco 94143, USA.
Am J Physiol. 1996 Jan;270(1 Pt 1):C12-30. doi: 10.1152/ajpcell.1996.270.1.C12.
This review summarizes recent progress in water-transporting mechanisms across cell membranes. Modern biophysical concepts of water transport and new measurement strategies are evaluated. A family of water-transporting proteins (water channels, aquaporins) has been identified, consisting of small hydrophobic proteins expressed widely in epithelial and nonepithelial tissues. The functional properties, genetics, and cellular distributions of these proteins are summarized. The majority of molecular-level information about water-transporting mechanisms comes from studies on CHIP28, a 28-kDa glycoprotein that forms tetramers in membranes; each monomer contains six putative helical domains surrounding a central aqueous pathway and functions independently as a water-selective channel. Only mutations in the vasopressin-sensitive water channel have been shown to cause human disease (non-X-linked congenital nephrogenic diabetes insipidus); the physiological significance of other water channels remains unproven. One mercurial-insensitive water channel has been identified, which has the unique feature of multiple overlapping transcriptional units. Systems for expression of water channel proteins are described, including Xenopus oocytes, mammalian and insect cells, and bacteria. Further work should be directed at elucidation of the role of water channels in normal physiology and disease, molecular analysis of regulatory mechanisms, and water channel structure determination at atomic resolution.
本综述总结了跨细胞膜水转运机制的最新进展。对水转运的现代生物物理概念和新的测量策略进行了评估。已鉴定出一类水转运蛋白（水通道，水孔蛋白），其由在上皮组织和非上皮组织中广泛表达的小疏水蛋白组成。总结了这些蛋白的功能特性、遗传学和细胞分布。关于水转运机制的大多数分子水平信息来自对CHIP28的研究，CHIP28是一种28 kDa的糖蛋白，在膜中形成四聚体；每个单体包含围绕中央水通道的六个假定螺旋结构域，并作为水选择性通道独立发挥作用。仅抗利尿激素敏感水通道的突变已被证明可导致人类疾病（非X连锁先天性肾性尿崩症）；其他水通道的生理意义仍未得到证实。已鉴定出一种对汞不敏感的水通道，其具有多个重叠转录单元的独特特征。描述了水通道蛋白的表达系统，包括非洲爪蟾卵母细胞、哺乳动物和昆虫细胞以及细菌。进一步的工作应致力于阐明水通道在正常生理和疾病中的作用、调节机制的分子分析以及原子分辨率下水通道结构的确定。
