Implications of the aquaporin-4 structure on array formation and cell adhesion.
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 3(10) 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.
Hiroaki
Yoko
Y
Department of Biophysics, Faculty of Science, Kyoto University, Kitashirakawa, Kyoto 606-8502, Japan.
Tani
Kazutoshi
K
Kamegawa
Akiko
A
Gyobu
Nobuhiko
N
Nishikawa
Kouki
K
Suzuki
Hiroshi
H
Walz
Thomas
T
Sasaki
Sei
S
Mitsuoka
Kaoru
K
Kimura
Kazushi
K
Mizoguchi
Akira
A
Fujiyoshi
Yoshinori
Y
D000595:Amino Acid Sequence; D000818:Animals; D051401:Aquaporin 4 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D002448:Cell Adhesion; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D007739:L Cells; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
C496032:Aqp4 protein, rat; D051401:Aquaporin 4