Differential effect of α-syntrophin knockout on aquaporin-4 and Kir4.1 expression in retinal macroglial cells in mice

• Main Authors: W. Puwarawuttipanit, A. D. Bragg, D. S. Frydenlund, M. N. Mylonakou, E. A. Nagelhus, M. F. Peters, N. Kotchabhakdi, M. E. Adams, S. C. Froehner, F. M. Haug, O. P. Ottersen, M. Amiry-Moghaddam
• Other Authors: Universitetet i Oslo
• Format: Article
• Published: 2018
• Subjects: Neuroscience
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/23889
• Institution: Mahidol University

Aquaporin-4 water channels and the inwardly rectifying potassium channels Kir4.1 are coexpressed in a highly polarized manner at the perivascular and subvitreal endfeet of retinal Müller cells and astrocytes. The present study was aimed at resolving the anchoring mechanisms responsible for the coexpression of these molecules. Both aquaporin-4 and Kir4.1 contain PDZ-domain binding motifs at their C-termini and it was recently shown that mice with targeted disruption of the dystrophin gene display altered distribution of aquaporin-4 and Kir4.1 in the retina. To test our hypothesis that α-syntrophin (a PDZ-domain containing protein of the dystrophin associated protein complex) is involved in aquaporin-4 and Kir4.1 anchoring in retinal cells, we studied the expression pattern of these molecules in α-syntrophin null mice. Judged by quantitative immunogold cytochemistry, deletion of the α-syntrophin gene causes a partial loss (by 70%) of aquaporin-4 labeling at astrocyte and Müller cell endfeet but no decrease in Kir4.1 labeling at these sites. These findings suggest that α-syntrophin is not involved in the anchoring of Kir4.1 and only partly responsible for the anchoring of aquaporin-4 in retinal endfeet membranes. Furthermore we show that wild type and α-syntrophin null mice exhibit strong β1 syntrophin labeling at perivascular and subvitreal Müller cell endfeet, raising the possibility that β1 syntrophin might be involved in the anchoring of Kir4.1 and the α-syntrophin independent pool of aquaporin-4. © 2005 Published by Elsevier Ltd on behalf of IBRO.