Structural function of MIP/aquaporin 0 in the eye lens; genetic defects lead to congenital inherited cataracts.
Structural function of MIP/aquaporin 0 in the eye lens; genetic defects lead to congenital inherited cataracts.
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DOI：
10.1007/978-3-540-79885-9_14
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发表时间：
2009-01-01
影响因子：
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通讯作者：
Chepelinsky, Ana B
中科院分区：
文献类型：
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作者：
Chepelinsky, Ana B
水通道蛋白 0 (AQP0) 最初被定性为膜内在蛋白，在眼晶状体的晶状体纤维中特异性表达，并指定为 MIP，代表晶状体的主要内在蛋白。一旦基因被克隆，就可以识别出一个内部重复序列，编码氨基酸 Asp-Pro-Ala，即 NPA 重复序列。不久，MIP 基因家族出现，其成员以哺乳动物、昆虫和植物为特征。 Peter Agre 的实验室开发出水通道功能测定法后，MIP 家族成为水通道蛋白家族，MIP 被称为水通道蛋白 0。除了充当水通道外，水通道蛋白 0 还发挥结构作用，是维持晶状体透明度和光学调节所必需的。人类和小鼠的 AQP0 基因突变会导致遗传性白内障；小鼠中 MIP/AQP0 基因的缺失导致缺乏维持晶状体纤维结构所需的缝合线形成，从而导致眼晶状体的调节和聚焦特性受到干扰。晶体学研究支持水通道蛋白 0 作为眼晶状体纤维中的水通道（开放构型）或粘附分子（封闭构型）的双重功能的概念。 MIP/AQP0 的功能既作为水通道又作为晶状体纤维中的粘附分子，有助于形成晶状体纤维的狭窄细胞间隙，这是晶状体透明和调节所需的。
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.