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Canonical Bone Morphogenetic Protein Signaling Regulates Expression of Aquaporin-4 and Its Anchoring Complex in Mouse Astrocytes
Aquaporin-4 (AQP4) is the predominant water channel in the brain; it is enriched in astrocytic foot processes abutting vessels where it is anchored through an interaction with the dystrophin-associated protein (DAP) complex. Enhanced expression with concomitant mislocalization of AQP4 along astrocyt...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9067306/ https://www.ncbi.nlm.nih.gov/pubmed/35518645 http://dx.doi.org/10.3389/fncel.2022.878154 |
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author | Skauli, Nadia Savchenko, Ekaterina Ottersen, Ole Petter Roybon, Laurent Amiry-Moghaddam, Mahmood |
author_facet | Skauli, Nadia Savchenko, Ekaterina Ottersen, Ole Petter Roybon, Laurent Amiry-Moghaddam, Mahmood |
author_sort | Skauli, Nadia |
collection | PubMed |
description | Aquaporin-4 (AQP4) is the predominant water channel in the brain; it is enriched in astrocytic foot processes abutting vessels where it is anchored through an interaction with the dystrophin-associated protein (DAP) complex. Enhanced expression with concomitant mislocalization of AQP4 along astrocyte plasma membranes is a hallmark of several neurological conditions. Thus, there is an urgent need to identify which signaling pathways dictate AQP4 microdistribution. Here we show that canonical bone morphogenetic proteins (BMPs), particularly BMP2 and 4, upregulate AQP4 expression in astrocytes and dysregulate the associated DAP complex by differentially affecting its individual members. We further demonstrate the presence of BMP receptors and Smad1/5/9 pathway activation in BMP treated astrocytes. Our analysis of adult mouse brain reveals BMP2 and 4 in neurons and in a subclass of endothelial cells and activated Smad1/5/9 in astrocytes. We conclude that the canonical BMP-signaling pathway might be responsible for regulating the expression of AQP4 and of DAP complex proteins that govern the subcellular compartmentation of this aquaporin. |
format | Online Article Text |
id | pubmed-9067306 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90673062022-05-04 Canonical Bone Morphogenetic Protein Signaling Regulates Expression of Aquaporin-4 and Its Anchoring Complex in Mouse Astrocytes Skauli, Nadia Savchenko, Ekaterina Ottersen, Ole Petter Roybon, Laurent Amiry-Moghaddam, Mahmood Front Cell Neurosci Neuroscience Aquaporin-4 (AQP4) is the predominant water channel in the brain; it is enriched in astrocytic foot processes abutting vessels where it is anchored through an interaction with the dystrophin-associated protein (DAP) complex. Enhanced expression with concomitant mislocalization of AQP4 along astrocyte plasma membranes is a hallmark of several neurological conditions. Thus, there is an urgent need to identify which signaling pathways dictate AQP4 microdistribution. Here we show that canonical bone morphogenetic proteins (BMPs), particularly BMP2 and 4, upregulate AQP4 expression in astrocytes and dysregulate the associated DAP complex by differentially affecting its individual members. We further demonstrate the presence of BMP receptors and Smad1/5/9 pathway activation in BMP treated astrocytes. Our analysis of adult mouse brain reveals BMP2 and 4 in neurons and in a subclass of endothelial cells and activated Smad1/5/9 in astrocytes. We conclude that the canonical BMP-signaling pathway might be responsible for regulating the expression of AQP4 and of DAP complex proteins that govern the subcellular compartmentation of this aquaporin. Frontiers Media S.A. 2022-04-20 /pmc/articles/PMC9067306/ /pubmed/35518645 http://dx.doi.org/10.3389/fncel.2022.878154 Text en Copyright © 2022 Skauli, Savchenko, Ottersen, Roybon and Amiry-Moghaddam. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Skauli, Nadia Savchenko, Ekaterina Ottersen, Ole Petter Roybon, Laurent Amiry-Moghaddam, Mahmood Canonical Bone Morphogenetic Protein Signaling Regulates Expression of Aquaporin-4 and Its Anchoring Complex in Mouse Astrocytes |
title | Canonical Bone Morphogenetic Protein Signaling Regulates Expression of Aquaporin-4 and Its Anchoring Complex in Mouse Astrocytes |
title_full | Canonical Bone Morphogenetic Protein Signaling Regulates Expression of Aquaporin-4 and Its Anchoring Complex in Mouse Astrocytes |
title_fullStr | Canonical Bone Morphogenetic Protein Signaling Regulates Expression of Aquaporin-4 and Its Anchoring Complex in Mouse Astrocytes |
title_full_unstemmed | Canonical Bone Morphogenetic Protein Signaling Regulates Expression of Aquaporin-4 and Its Anchoring Complex in Mouse Astrocytes |
title_short | Canonical Bone Morphogenetic Protein Signaling Regulates Expression of Aquaporin-4 and Its Anchoring Complex in Mouse Astrocytes |
title_sort | canonical bone morphogenetic protein signaling regulates expression of aquaporin-4 and its anchoring complex in mouse astrocytes |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9067306/ https://www.ncbi.nlm.nih.gov/pubmed/35518645 http://dx.doi.org/10.3389/fncel.2022.878154 |
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