Abstract
Aquaporin 4 (AQP4) is expressed in the perivascular glial endfeet and is an important pathway for water during formation and resolution of brain edema. In this study, we examined the functional properties and relative unit water permeability of three functional isoforms of AQP4 expressed in the brain (M1, M23, Mz). The M23 isoform gave rise to square arrays when expressed in Xenopus laevis oocytes. The relative unit water permeability differed significantly between the isoforms in the order of M1 > Mz > M23. None of the three isoforms were permeable to small osmolytes nor were they affected by changes in external K+ concentration. Upon protein kinase C (PKC) activation, oocytes expressing the three isoforms demonstrated rapid reduction of water permeability, which correlated with AQP4 internalization. The M23 isoform was more sensitive to PKC regulation than the longer isoforms and was internalized significantly faster. Our results suggest a specific role for square array formation.
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Acknowledgments
Technical assistance was provided by Charlotte G. Iversen, Mikkel Olsen, and Inger Merete Paulsen. The authors wish to give special thanks to Karen Thomsen for expert freeze fracture studies. The study was supported by the Nordic Centre of Excellence in Water-Imbalance Related Disorders, the Lundbeck Foundation (to N.M.), the Danish Medical Research Council (FSS) (to N.M., R.A.F.), E. Danielsen’s Foundation (to N.M.), the Augustinus Foundation (to N.M.), the Michaelsen’s Foundation (to N.M.), the Novo Nordisk Foundation (to R.A.F.), the Carlsberg Foundation (to R.A.F.) and the L’Oreal/UNESCO/Royal Danish Academy of Sciences Scholarship to Young Women in Science (to N.M.), Heart–Lung Foundation (to M.Z.), and the Functional genomics program of the Norwegian Research Council, FUGE (to T.H.). Additional funding to R.A.F was provided by a Marie Curie Intra-European Fellowship. The Water and Salt Research Center at the University of Aarhus is established and supported by the Danish National Research Foundation (Danmarks Grundforskningsfond).
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All authors belong to Nordic Center of Excellence for Water Imbalance Related Disorders.
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18_2009_218_MOESM1_ESM.tif
Supplementary Fig. 1. The M23 isoform forms square arrays in Xenopus laevis oocytes. Each row of panels represents images from different oocytes. At low magnification (A and D), the distinct boundary of the oocyte plasma membrane can be observed. The boxes show the areas magnified in (B and E). Square arrays were detected in the extensive invaginations of the oocyte plasma membrane. At high magnification (C and F), arrays are observed in both the P- and E-faces. (TIFF 2167 kb)
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Fenton, R.A., Moeller, H.B., Zelenina, M. et al. Differential water permeability and regulation of three aquaporin 4 isoforms. Cell. Mol. Life Sci. 67, 829–840 (2010). https://doi.org/10.1007/s00018-009-0218-9
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DOI: https://doi.org/10.1007/s00018-009-0218-9