Nielsen S, Smith B L, Christensen E I, Agre P
Department of Cell Biology, University of Aarhus, Denmark.
Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7275-9. doi: 10.1073/pnas.90.15.7275.
The existence of water-selective channels has been postulated to explain the high water permeability of erythrocytes and certain epithelial cells. The aquaporin CHIP (channel-forming integral membrane protein of 28 kDa), a molecular water channel, is abundant in erythrocytes and water-permeable segments of the nephron. To determine whether CHIP may mediate transmembrane water movement in other water-permeable epithelia, membranes of multiple organs were studied by immunoblotting, immunohistochemistry, and immunoelectron microscopy using affinity-purified anti-CHIP IgG. The apical membrane of the choroid plexus epithelium was densely stained, implying a role for CHIP in the secretion of cerebrospinal fluid. In the eye, CHIP was abundant in apical and basolateral domains of ciliary epithelium, the site of aqueous humor secretion, and also in lens epithelium and corneal endothelium. CHIP was detected in membranes of hepatic bile ducts and water-resorptive epithelium of gall bladder, suggesting a role in bile secretion and concentration. CHIP was not detected in glandular epithelium of mammary, salivary, or lacrimal glands, suggesting the existence of other water-channel isoforms. CHIP was also not detected within the epithelium of the gastrointestinal mucosa. CHIP was abundant in membranes of intestinal lacteals and continuous capillaries in diverse tissues, including cardiac and skeletal muscle, thus providing a molecular explanation for the known water permeability of certain lymphatics and capillary beds. These studies underscore the hypothesis that CHIP plays a major role in transcellular water movement throughout the body.
水选择性通道的存在被认为是用来解释红细胞和某些上皮细胞的高水渗透性的。水通道蛋白CHIP(28 kDa的形成通道的整合膜蛋白),一种分子水通道,在红细胞和肾单位的水通透段中含量丰富。为了确定CHIP是否可能介导其他水通透上皮细胞中的跨膜水转运,使用亲和纯化的抗CHIP IgG,通过免疫印迹、免疫组织化学和免疫电子显微镜对多个器官的膜进行了研究。脉络丛上皮的顶端膜被密集染色,这意味着CHIP在脑脊液分泌中起作用。在眼睛中,CHIP在睫状体上皮的顶端和基底外侧区域含量丰富,睫状体上皮是房水分泌的部位,在晶状体上皮和角膜内皮中也含量丰富。在肝内胆管和胆囊的水重吸收上皮的膜中检测到CHIP,表明其在胆汁分泌和浓缩中起作用。在乳腺、唾液腺或泪腺的腺上皮中未检测到CHIP,这表明存在其他水通道亚型。在胃肠道黏膜上皮内也未检测到CHIP。CHIP在肠乳糜管和包括心脏和骨骼肌在内的各种组织中的连续毛细血管的膜中含量丰富,从而为某些淋巴管和毛细血管床已知的水渗透性提供了分子解释。这些研究强调了CHIP在全身跨细胞水转运中起主要作用的假说。