AQPO-LTR of the CatFr mouse alters water permeability and calcium regulation of wild type AQP0
AQPO-LTR of the CatFr mouse alters water permeability and calcium regulation of wild type AQP0
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DOI：
10.1016/j.bbamem.2006.01.015
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发表时间：
2006-08-01
影响因子：
3.4
通讯作者：
Hall, James E.
中科院分区：
文献类型：
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作者：
Kalman, Katalin;Nemeth-Cahalan, Karin L.;Hall, James E.
水通道蛋白0（Aquaporin 0，AQP 0）是透镜的主要内在蛋白，其水渗透性可受pH和Ca ~（2+）的调节。白内障Fraser（Cat（Fr））小鼠在亚细胞区室中积累异常AQP 0（AQP 0-LTR），导致先天性白内障。我们研究了AQP 0-LTR在三个系统中对AQP 0正常功能的干扰。首先，我们建立了在透镜中表达AQP 0和AQP 0-LTR的转基因小鼠。AQP 0的表达不能预防先天性白内障，但能改善透镜的大小和透明度。第二，我们测量了水通道蛋白0与水通道蛋白0-LTR共表达在非洲爪蟾卵母细胞的水渗透性。AQP 0-LTR的低表达水平降低了AQP 0的水渗透性，高表达水平消除了其钙调节。第三，我们研究了AQP 0和AQP 0-LTR在转染的透镜上皮细胞中的运输。在低表达水平时，AQP 0-LTR随AQP 0向细胞膜迁移，而在高表达水平时，它聚集在亚细胞区室中。AQP 0-LTR对透镜发育的有害作用可能通过降低水渗透性和取消AQP 0的钙调节来解释。这项研究提供了第一个证据表明，钙调节水通道蛋白0的水渗透性可能是至关重要的维持正常的透镜的稳态和发展。(c)2006 Elsevier B. V.保留所有权利。
Aquaporin 0 (AQP0) is the major intrinsic protein of the lens and its water permeability can be modulated by changes in pH and Ca2+. The Cataract Fraser (Cat(Fr)) mouse accumulates an aberrant AQP0 (AQP0-LTR) in sub-cellular compartments resulting in a congenital cataract. We investigated the interference of AQP0-LTR with normal function of AQP0 in three systems. First, we created a transgenic mouse expressing AQP0 and AQP0-LTR in the lens. Expression of AQP0 did not prevent the congenital cataract but improved the size and transparency of the lens. Second, we measured water permeability of AQP0 co-expressed with AQP0-LTR in Xenopus oocytes. A low expression level of AQP0-LTR decreased the water permeability of AQP0, and a high expression level eliminated its calcium regulation. Third, we studied trafficking of AQP0 and AQP0-LTR in transfected lens epithelial cells. At low expression level, AQP0-LTR migrated with AQP0 toward the cell membrane, but at high expression level, it accumulated in sub-cellular compartments. The deleterious effect of AQP0-LTR on lens development may be explained by lowering water permeability and abolishing calcium regulation of AQP0. This study provides the first evidence that calcium regulation of AQP0 water permeability may be crucial for maintaining normal lens homeostasis and development. (c) 2006 Elsevier B.V. All rights reserved.