Implications of the aquaporin-4 structure on array formation and cell adhesion

被引：310

作者：

Hiroaki, Y

Tani, K

Kamegawa, A

Gyobu, N

Nishikawa, K

Suzuki, H

Walz, T

Sasaki, S

Mitsuoka, K

Kimura, K

Mizoguchi, A

Fujiyoshi, Y ^{[1
]}

机构：

[1] Kyoto Univ, Fac Sci, Dept Biophys, Sakyo Ku, Kyoto 6068502, Japan

[2] JST, CREST, Sakyo Ku, Kyoto 6068502, Japan

[3] AIST, BIRC, Koto Ku, Tokyo 1350064, Japan

[4] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA

[5] Tokyo Med & Dent Univ, Grad Sch, Dept Nephrol, Tokyo 1138519, Japan

[6] Mie Univ, Sch Med, Dept Anat, Tsu, Mie 5140001, Japan

来源：

JOURNAL OF MOLECULAR BIOLOGY | 2006年 / 355卷 / 04期

基金：

日本科学技术振兴机构;

关键词：

water channel; electron crystallography; cell adhesion; orthogonal array; glial lamellae;

D O I：

10.1016/j.jmb.2005.10.081

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：628 / 639

页数：12