Functional and molecular characterization of the human neutral solute channel aquaporin-9
Functional and molecular characterization of the human neutral solute channel aquaporin-9
复制标题
DOI：
10.1152/ajprenal.1999.277.5.f685
复制
发表时间：
1999-11-01
影响因子：
4.2
通讯作者：
Hediger, MA
中科院分区：
文献类型：
--
作者：
Tsukaguchi, H;Weremowicz, S;Hediger, MA
人中性溶质通道水通道蛋白9的功能和分子特征。在代谢活跃的细胞中，水和溶质的协调运输对于维持渗透稳态是重要的。最近，我们确定了一个广泛的选择性中性溶质通道，AQP 9，从大鼠肝脏，允许通过各种各样的水和中性溶质。人类同源物（hAQP 9）与大鼠AQP 9（rAQP 9）有76%的氨基酸序列同一性，但其渗透性被发现仅限于水和尿素。在这里，我们报告了重新评估的功能特性的AQP 9，其组织分布，其基因的结构，其染色体定位。当在非洲爪蟾卵母细胞中表达时，hAQP 9允许以根皮素和汞敏感的方式通过各种不带电的溶质，包括脲、多元醇、嘌呤和嘧啶。这些功能特征与rAQP 9相似。基于北方印迹分析，大鼠和人的AQP 9都在肝脏中大量表达，而与rAQP 9相反，hAQP 9也在外周白细胞和聚集白细胞的组织（如肺、脾和骨髓）中表达。人类AQP 9基因由6个外显子和5个内含子组成，分布在大约25 kb的区域内。基因组织与人类AQP 3和AQP 7的报告惊人地相似，表明它们是从共同的祖先基因进化而来的。启动子区含有假定的张力和糖皮质激素反应元件，表明AQP 9可能受渗透压和catalysts调节。荧光原位杂交将其位点定位于染色体15 q22.1-22.2。我们的数据表明，hAQP 9作为在肝脏和外周白细胞中表达的混杂溶质通道，在那里它非常适合于将代谢物和/或营养物质转运进出这些细胞。
Functional and molecular characterization of the human neutral solute channel aquaporin-9. In metabolically active cells, the coordinated transport of water and solutes is important for maintaining osmotic homeostasis. We recently identified a broad selective-neutral solute channel, AQP9, from rat liver that allows the passage of a wide variety of water and neutral solutes . A human homolog (hAQP9) with 76% amino acid sequence identity to rat AQP9 (rAQP9) was described, but its permeability was found to be restricted to water and urea. Here we report a reevaluation of the functional characteristics of hAQP9, its tissue distribution, the structure of its gene, and its chromosomal localization. When expressed in Xenopus oocytes, hAQP9 allowed passage of a wide variety of noncharged solutes, including carbamides, polyols, purines, and pyrimidines in a phloretin- and mercurial-sensitive manner. These functional characteristics are similar to those of rAQP9. Based on Northern blot analysis, both rat and human AQP9 are abundantly expressed in liver, whereas, in contrast to rAQP9, hAQP9 is also expressed in peripheral leukocytes and in tissues that accumulate leukocytes, such as lung, spleen, and bone marrow. The human AQP9 gene is composed of 6 exons and 5 introns distributed over approximately similar to 25 kb. The gene organization is strikingly similar to that reported for human AQP3 and AQP7, suggesting their evolution from a common ancestral gene. The promoter region contains putative tonicity and glucocorticoid-responsive elements, suggesting that AQP9 may be regulated by osmolality and catabolism. Fluorescence in situ hybridization assigned its locus to chromosome 15 q22.1-22.2, Our data show that hAQP9 serves as a promiscuous solute channel expressed in both liver and peripheral leukocytes, where it is ideally suited to transport of metabolites and/or nutrients into and out of these cells.