Aquaporin-4

Abstract

In human body, there are thirteen water channels but their expression patterns are tissue specific. Aquaporin-4 (AQP4) is a predominantly expressed water channel in the mammalian brain and an important drug target for treatment of cerebral edema, bipolar disorder, and mesial temporal lobe epilepsy. Recently it was reported that IgG of optic-spinal multiple sclerosis patients bound to AQP4. In order to reveal the function of AQP4, we determined the atomic structure of AQP4 by electron crystallography of double layered two-dimensional crystals. In double layered crystal, each single layered crystal contacts by a short 310 helix in the extracellular loop C. It would suggest that AQP4 shows the weak adhesive activity between adjoining membranes. This is correlated to immunogold labeling of AQP4 in glial lamellae localizing the protein areas where the membranes are separated but also all along junctional regions. Furthermore, from the freeze fracture replica labeling and the mutational experiment, the palmitoylation of N-terminal cysteine residues makes orthogonal array structure unstable on Chinese hamster Ovary (CHO) cell membrane. These findings suggest that there must be the complicated mechanism for control of water content relevant to AQP4 within the brain.