Chepelinsky Ana B
National Institutes of Health, National Eye Institute, Bldg. 31, Room 6A-32, Bethesda, MD, 20892-2510, USA.
Handb Exp Pharmacol. 2009(190):265-97. doi: 10.1007/978-3-540-79885-9_14.
Aquaporin 0 (AQP0) was originally characterized as a membrane intrinsic protein, specifically expressed in the lens fibers of the ocular lens and designated MIP, for major intrinsic protein of the lens. Once the gene was cloned, an internal repeat was identified, encoding for the amino acids Asp-Pro-Ala, the NPA repeat. Shortly, the MIP gene family was emerging, with members being characterized in mammals, insects, and plants. Once Peter Agre's laboratory developed a functional assay for water channels, the MIP family became the aquaporin family and MIP became known as aquaporin 0. Besides functioning as a water channel, aquaporin 0 also plays a structural role, being required for maintaining the transparency and optical accommodation of the ocular lens. Mutations in the AQP0 gene in human and mice result in genetic cataracts; deletion of the MIP/AQP0 gene in mice results in lack of suture formation required for maintenance of the lens fiber architecture, resulting in perturbed accommodation and focus properties of the ocular lens. Crystallography studies support the notion of the double function of aquaporin 0 as a water channel (open configuration) or adhesion molecule (closed configuration) in the ocular lens fibers. The functions of MIP/AQP0, both as a water channel and an adhesive molecule in the lens fibers, contribute to the narrow intercellular space of the lens fibers that is required for lens transparency and accommodation.
水通道蛋白0（AQP0）最初被鉴定为一种膜内在蛋白，在晶状体的晶状体纤维中特异性表达，并被命名为MIP，即晶状体主要内在蛋白。该基因被克隆后，发现了一个内部重复序列，编码天冬氨酸-脯氨酸-丙氨酸氨基酸序列，即NPA重复序列。不久之后，MIP基因家族开始出现，其成员在哺乳动物、昆虫和植物中得到了鉴定。彼得·阿格雷实验室开发出一种水通道功能检测方法后，MIP家族就成了水通道蛋白家族，MIP也被称为水通道蛋白0。除了作为水通道发挥作用外，水通道蛋白0还具有结构作用，是维持晶状体透明度和光学调节所必需的。人类和小鼠AQP0基因的突变会导致遗传性白内障；小鼠中MIP/AQP0基因的缺失会导致维持晶状体纤维结构所需的缝合线形成缺失，从而导致晶状体调节和聚焦特性受到干扰。晶体学研究支持了水通道蛋白0在晶状体纤维中作为水通道（开放构型）或黏附分子（封闭构型）具有双重功能的观点。MIP/AQP0在晶状体纤维中作为水通道和黏附分子的功能，有助于形成晶状体纤维狭窄的细胞间隙，这是晶状体透明度和调节功能所必需的。
