Department of Genetics, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Chennai, India.
Exp Eye Res. 2013 May;110:136-41. doi: 10.1016/j.exer.2012.10.010. Epub 2012 Oct 29.
Autosomal dominant congenital cataracts have been associated with mutations of genes encoding several soluble and membrane proteins. By candidate gene screening, we identified a novel mutation in MIP (c.494 G > A) that segregates with a congenital lamellar cataract within a south Indian family and causes the replacement of a highly conserved glycine by aspartate (G165D) within aquaporin0 (AQP0). Unlike wild type AQP0, expression of AQP0-G165D in Xenopus oocytes did not facilitate swelling in hypotonic medium. In transfected HeLa cells, wild type AQP0 localized at the plasma membrane while AQP0-G165D was retained within the secretory pathway, and localized mainly within the endoplasmic reticulum. These results suggest that mutation of this conserved glycine residue leads to improper trafficking of AQP0-G165D and loss of water channel function. They emphasize the importance of AQP0 for maintenance of lens transparency and identify a critical residue that is conserved among aquaporins, but has not previously been associated with disease-associated replacement.
常染色体显性先天性白内障与编码几种可溶性和膜蛋白的基因突变有关。通过候选基因筛查，我们在一个印度南部家族中发现了一个与先天性板层白内障相关的 MIP 新突变(c.494 G > A)，该突变导致水通道蛋白 0 (AQP0) 内高度保守的甘氨酸被天冬氨酸取代(G165D)。与野生型 AQP0 不同，AQP0-G165D 在非洲爪蟾卵母细胞中的表达不能促进低渗介质中的肿胀。在转染的 HeLa 细胞中，野生型 AQP0 定位于质膜，而 AQP0-G165D 则保留在内分泌途径中，主要定位于内质网内。这些结果表明，该保守甘氨酸残基的突变导致 AQP0-G165D 的错误运输和水通道功能丧失。它们强调了 AQP0 对于维持晶状体透明度的重要性，并确定了一个在水通道蛋白中保守但以前与疾病相关替代无关的关键残基。
