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Canonical Bone Morphogenetic Protein Signaling Regulates Expression of Aquaporin-4 and Its Anchoring Complex in Mouse Astrocytes

Skauli, Nadia ; Savchenko, Ekaterina LU ; Ottersen, Ole Petter ; Roybon, Laurent LU and Amiry-Moghaddam, Mahmood (2022) In Frontiers in Cellular Neuroscience 16.
Abstract

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... (More)

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.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
aquaporin-4, astrocyte, bone morphogenetic protein, dystrophin, Smad1/5/9
in
Frontiers in Cellular Neuroscience
volume
16
article number
878154
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85129514947
  • pmid:35518645
ISSN
1662-5102
DOI
10.3389/fncel.2022.878154
language
English
LU publication?
yes
id
9469afae-1553-4ff3-bb9d-1d77222be8eb
date added to LUP
2022-07-07 13:41:15
date last changed
2024-06-27 15:32:09
@article{9469afae-1553-4ff3-bb9d-1d77222be8eb,
  abstract     = {{<p>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.</p>}},
  author       = {{Skauli, Nadia and Savchenko, Ekaterina and Ottersen, Ole Petter and Roybon, Laurent and Amiry-Moghaddam, Mahmood}},
  issn         = {{1662-5102}},
  keywords     = {{aquaporin-4; astrocyte; bone morphogenetic protein; dystrophin; Smad1/5/9}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Cellular Neuroscience}},
  title        = {{Canonical Bone Morphogenetic Protein Signaling Regulates Expression of Aquaporin-4 and Its Anchoring Complex in Mouse Astrocytes}},
  url          = {{http://dx.doi.org/10.3389/fncel.2022.878154}},
  doi          = {{10.3389/fncel.2022.878154}},
  volume       = {{16}},
  year         = {{2022}},
}