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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
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. |
format | Online Article Text |
id | pubmed-7072498 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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