Implications of the aquaporin-4 structure on array formation and cell adhesion
Implications of the aquaporin-4 structure on array formation and cell adhesion
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DOI：
10.1016/j.jmb.2005.10.081
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发表时间：
2006-01-27
影响因子：
5.6
通讯作者：
Fujiyoshi, Y
中科院分区：
文献类型：
--
作者：
Hiroaki, Y;Tani, K;Fujiyoshi, Y
水通道蛋白-4(Aquaporin-4，AQP4)是哺乳动物脑内主要的水通道，是治疗脑水肿、双相情感障碍和内侧颞叶癫痫的重要药物靶点。我们用双层二维晶体的电子结晶学确定了AQP4的结构。这种结构使我们能够讨论AQP4剪接变异体的长和短之间的表达比例如何决定体内正交表的大小。此外，AQP4在胞外环中含有一个短的310螺旋，它介导相邻膜上AQP4分子之间的弱而特异的相互作用。这一发现表明，AQP4在细胞黏附中扮演了以前意想不到的角色。AQP4在L细胞中的表达证实了这一观点，导致了细胞的聚集。因此，我们的AQP4结构使我们能够提出正交表的大小调节和通道介导的细胞黏附的模型。(C)2005爱思唯尔有限公司。保留所有权利。
Aquaporin-4 (AQP4) is the predominant water channel in the mammalian brain and an important drug target for treatment of cerebral edema, bipolar disorder and mesial temporal lobe epilepsy. We determined the AQP4 structure by electron crystallography of double-layered, two-dimensional (2D) crystals. The structure allows us to discuss how the expression ratio between the long and short AQP4 splicing variant can determine the size of in vivo orthogonal arrays. Furthermore, AQP4 contains a short 310 helix in an extracellular loop, which mediates weak but specific interactions between AQP4 molecules in adjoining membranes. This finding suggests a previously unexpected role for AQP4 in cell adhesion. This notion was corroborated by expression of AQP4 in L-cells, which resulted in clustering of the cells. Our AQP4 structure thus enables us to propose models for the size regulation of orthogonal arrays and channel-mediated cell adhesion. (c) 2005 Elsevier Ltd. All rights reserved.