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Uncoupling of the Astrocyte Syncytium Differentially Affects AQP4 Isoforms

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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072498/
https://www.ncbi.nlm.nih.gov/pubmed/32046059
http://dx.doi.org/10.3390/cells9020382
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author 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
author_facet 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
author_sort Katoozi, Shirin
collection PubMed
description 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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spelling pubmed-70724982020-03-19 Uncoupling of the Astrocyte Syncytium Differentially Affects AQP4 Isoforms 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 Cells Article 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. MDPI 2020-02-07 /pmc/articles/PMC7072498/ /pubmed/32046059 http://dx.doi.org/10.3390/cells9020382 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
Uncoupling of the Astrocyte Syncytium Differentially Affects AQP4 Isoforms
title Uncoupling of the Astrocyte Syncytium Differentially Affects AQP4 Isoforms
title_full Uncoupling of the Astrocyte Syncytium Differentially Affects AQP4 Isoforms
title_fullStr Uncoupling of the Astrocyte Syncytium Differentially Affects AQP4 Isoforms
title_full_unstemmed Uncoupling of the Astrocyte Syncytium Differentially Affects AQP4 Isoforms
title_short Uncoupling of the Astrocyte Syncytium Differentially Affects AQP4 Isoforms
title_sort uncoupling of the astrocyte syncytium differentially affects aqp4 isoforms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072498/
https://www.ncbi.nlm.nih.gov/pubmed/32046059
http://dx.doi.org/10.3390/cells9020382
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