Uncoupling of the Astrocyte Syncytium Differentially Affects AQP4 Isoforms
Shirin Katoozi,
Nadia Skauli,
Soulmaz Zahl,
Tushar Deshpande,
Pascal Ezan,
Claudia Palazzo,
Christian Steinhäuser,
Antonio Frigeri,
Martine Cohen-Salmon,
Ole Petter Ottersen,
Mahmood Amiry-Moghaddam
Affiliations
Shirin Katoozi
Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo; 0315 Oslo, Norway
Nadia Skauli
Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo; 0315 Oslo, Norway
Soulmaz Zahl
Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo; 0315 Oslo, Norway
Tushar Deshpande
Institute of Cellular Neuroscience, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
Pascal Ezan
Physiology and Physiopathology of the Gliovascular Unit Research Group. Center for Interdisciplinary Research in Biology (CIRB), College de France, Unité Mixte de Recherche 7241 CNRS, Unité1050 INSERM, PSL Research University, 75005 Paris, France
Claudia Palazzo
Department of Basic Medical Sciences, Neurosciences and Sense Organs, School of Medicine, University of Bari Aldo Moro, 70124 Bari, Italy
Christian Steinhäuser
Institute of Cellular Neuroscience, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
Antonio Frigeri
Department of Basic Medical Sciences, Neurosciences and Sense Organs, School of Medicine, University of Bari Aldo Moro, 70124 Bari, Italy
Martine Cohen-Salmon
Physiology and Physiopathology of the Gliovascular Unit Research Group. Center for Interdisciplinary Research in Biology (CIRB), College de France, Unité Mixte de Recherche 7241 CNRS, Unité1050 INSERM, PSL Research University, 75005 Paris, France
Ole Petter Ottersen
Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo; 0315 Oslo, Norway
Mahmood Amiry-Moghaddam
Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo; 0315 Oslo, Norway
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.
