Uncoupling of the Astrocyte Syncytium Differentially Affects AQP4 Isoforms.

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ID: 107257
2020
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Abstract
The water channel protein aquaporin-4 (AQP4) and the gap junction forming proteins connexin-43 (Cx43) and connexin-30 (Cx30) are astrocytic proteins critically involved in brain water and ion homeostasis. While AQP4 is mainly involved in water flux across the astrocytic endfeet membranes, astrocytic gap junctions provide syncytial coupling allowing intercellular exchange of water, ions, and other molecules. We have previously shown that mice with targeted deletion of Aqp4 display enhanced gap junctional coupling between astrocytes. Here, we investigate whether uncoupling of the astrocytic syncytium by deletion of the astrocytic connexins Cx43 and Cx30 affects AQP4 membrane localization and expression. By using quantitative immunogold cytochemistry, we show that deletion of astrocytic connexins leads to a substantial reduction of perivascular AQP4, concomitant with a down-regulation of total AQP4 protein and mRNA. Isoform expression analysis shows that while the level of the predominant AQP4 M23 isoform is reduced in Cx43/Cx30 double deficient hippocampal astrocytes, the levels of M1, and the alternative translation AQP4ex isoform protein levels are increased. These findings reveal a complex interdependence between AQP4 and connexins, which are both significantly involved in homeostatic functions and astrogliopathologies.
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katoozi2020uncouplingcells Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Katoozi, Shirin;Skauli, Nadia;Zahl, Soulmaz;Deshpande, Tushar;Ezan, Pascal;Palazzo, Claudia;Steinhäuser, Christian;Frigeri, Antonio;Cohen-Salmon, Martine;Ottersen, Ole Petter;Amiry-Moghaddam, Mahmood;
Journal Cells
Year 2020
DOI
E382
URL
Keywords
astrocytes polarization gap junction aqp4 cx30 cx43

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