title: Implications of the aquaporin-4 structure on array formation and cell adhesion.
abstract: 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.
authors.affiliation: Department of Biophysics, Faculty of Science, Kyoto University, Kitashirakawa, Kyoto 606-8502, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hiroaki
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Tani
authors.forename: Akiko
authors.initials: A
authors.lastname: Kamegawa
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Gyobu
authors.forename: Kouki
authors.initials: K
authors.lastname: Nishikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Thomas
authors.initials: T
authors.lastname: Walz
authors.forename: Sei
authors.initials: S
authors.lastname: Sasaki
authors.forename: Kaoru
authors.initials: K
authors.lastname: Mitsuoka
authors.forename: Kazushi
authors.initials: K
authors.lastname: Kimura
authors.forename: Akira
authors.initials: A
authors.lastname: Mizoguchi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fujiyoshi
mesh_terms: 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
chemical_list: C496032:Aqp4 protein, rat; D051401:Aquaporin 4