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Regulation and Function of AQP4 in the Central Nervous System

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Abstract

Aquaporin 4 (AQP4) is the predominant water channel in the mammalian brain and is mainly expressed in the perivascular glial endfeet at the brain–blood interface. Based on studies on AQP4−/− mice, AQP4 has been assigned physiological roles in stimulus-induced K+ clearance, paravascular fluid flow, and brain edema formation. Conflicting data have been presented on the role of AQP4 in K+ clearance and associated extracellular space shrinkage and on the stroke-induced alterations of AQP4 expression levels during edema formation, raising questions about the functional importance of AQP4 in these (patho)physiological aspects. Phosphorylation-dependent gating of AQP4 has been proposed as a regulatory mechanism for AQP4-mediated osmotic water transport. This paradigm was, however, recently challenged by experimental evidence and molecular dynamics simulations. Regulatory patterns and physiological roles for AQP4 thus remain to be fully explored.

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Acknowledgments

We are grateful for technical assistance provided by Charlotte Goos Iversen and Catia Correa Goncalves Andersen. These projects were funded by Lundbeck Foundation, the Danish Medical Research Council, and the Novo Nordic Foundation (to NM).

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  1. Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, Bldg. 12.6, 2200, Copenhagen, Denmark

    Mette Assentoft, Brian Roland Larsen & Nanna MacAulay

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  1. Mette Assentoft
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  2. Brian Roland Larsen
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Correspondence to Nanna MacAulay.

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Special Issue: In Honor of Dr. Gerald Dienel.

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Assentoft, M., Larsen, B.R. & MacAulay, N. Regulation and Function of AQP4 in the Central Nervous System. Neurochem Res 40, 2615–2627 (2015). https://doi.org/10.1007/s11064-015-1519-z

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