Cargando…
Tissue Distribution of the Readthrough Isoform of AQP4 Reveals a Dual Role of AQP4ex Limited to CNS
Translational readthrough (TRT) of aquaporin-4 (AQP4) has remarkably expanded the importance of this new post-transcriptional mechanism, as well as the regulation potential of AQP4. The TRT isoform of AQP4, named AQP4ex, is central for both AQP4 polarization and water channel activity in the central...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073200/ https://www.ncbi.nlm.nih.gov/pubmed/32102323 http://dx.doi.org/10.3390/ijms21041531 |
_version_ | 1783506583154589696 |
---|---|
author | Palazzo, Claudia Abbrescia, Pasqua Valente, Onofrio Nicchia, Grazia Paola Banitalebi, Shervin Amiry-Moghaddam, Mahmood Trojano, Maria Frigeri, Antonio |
author_facet | Palazzo, Claudia Abbrescia, Pasqua Valente, Onofrio Nicchia, Grazia Paola Banitalebi, Shervin Amiry-Moghaddam, Mahmood Trojano, Maria Frigeri, Antonio |
author_sort | Palazzo, Claudia |
collection | PubMed |
description | Translational readthrough (TRT) of aquaporin-4 (AQP4) has remarkably expanded the importance of this new post-transcriptional mechanism, as well as the regulation potential of AQP4. The TRT isoform of AQP4, named AQP4ex, is central for both AQP4 polarization and water channel activity in the central nervous system (CNS). Here we evaluate the relevance of the TRT mechanism by analyzing whether AQP4ex is also expressed in peripheral tissues and whether the expression of AQP4ex is necessary for its polarized expression as it occurs in perivascular astrocyte processes. To this purpose, AQP4ex null mice were used, and analysis was performed by immunolocalization and immunoblot. The results demonstrate that AQP4ex is expressed in kidney, stomach, trachea and skeletal muscle with the same localization pattern as the canonical AQP4 isoforms. AQP4ex protein levels vary from 6% to about 13% of the total AQP4 protein levels in peripheral tissues. Immunogold electron microscopy experiments demonstrated the localization of AQP4ex at the astrocytic endfeet, and experiments conducted on AQP4ex null mice CNS confirmed that the expression of AQP4ex is necessary for anchoring of the perivascular AQP4. Without the readthrough isoform, AQP4 assemblies are mis-localized, being uniformly distributed on the astrocyte processes facing the neuropile. No alteration of AQP4 polarization was found in AQP4ex null kidney, stomach, trachea or skeletal muscle, suggesting that AQP4ex does not have a role for proper membrane localization of AQP4 in peripheral tissues. We conclude that a dual role for AQP4ex is limited to the CNS. |
format | Online Article Text |
id | pubmed-7073200 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70732002020-03-19 Tissue Distribution of the Readthrough Isoform of AQP4 Reveals a Dual Role of AQP4ex Limited to CNS Palazzo, Claudia Abbrescia, Pasqua Valente, Onofrio Nicchia, Grazia Paola Banitalebi, Shervin Amiry-Moghaddam, Mahmood Trojano, Maria Frigeri, Antonio Int J Mol Sci Article Translational readthrough (TRT) of aquaporin-4 (AQP4) has remarkably expanded the importance of this new post-transcriptional mechanism, as well as the regulation potential of AQP4. The TRT isoform of AQP4, named AQP4ex, is central for both AQP4 polarization and water channel activity in the central nervous system (CNS). Here we evaluate the relevance of the TRT mechanism by analyzing whether AQP4ex is also expressed in peripheral tissues and whether the expression of AQP4ex is necessary for its polarized expression as it occurs in perivascular astrocyte processes. To this purpose, AQP4ex null mice were used, and analysis was performed by immunolocalization and immunoblot. The results demonstrate that AQP4ex is expressed in kidney, stomach, trachea and skeletal muscle with the same localization pattern as the canonical AQP4 isoforms. AQP4ex protein levels vary from 6% to about 13% of the total AQP4 protein levels in peripheral tissues. Immunogold electron microscopy experiments demonstrated the localization of AQP4ex at the astrocytic endfeet, and experiments conducted on AQP4ex null mice CNS confirmed that the expression of AQP4ex is necessary for anchoring of the perivascular AQP4. Without the readthrough isoform, AQP4 assemblies are mis-localized, being uniformly distributed on the astrocyte processes facing the neuropile. No alteration of AQP4 polarization was found in AQP4ex null kidney, stomach, trachea or skeletal muscle, suggesting that AQP4ex does not have a role for proper membrane localization of AQP4 in peripheral tissues. We conclude that a dual role for AQP4ex is limited to the CNS. MDPI 2020-02-24 /pmc/articles/PMC7073200/ /pubmed/32102323 http://dx.doi.org/10.3390/ijms21041531 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 Palazzo, Claudia Abbrescia, Pasqua Valente, Onofrio Nicchia, Grazia Paola Banitalebi, Shervin Amiry-Moghaddam, Mahmood Trojano, Maria Frigeri, Antonio Tissue Distribution of the Readthrough Isoform of AQP4 Reveals a Dual Role of AQP4ex Limited to CNS |
title | Tissue Distribution of the Readthrough Isoform of AQP4 Reveals a Dual Role of AQP4ex Limited to CNS |
title_full | Tissue Distribution of the Readthrough Isoform of AQP4 Reveals a Dual Role of AQP4ex Limited to CNS |
title_fullStr | Tissue Distribution of the Readthrough Isoform of AQP4 Reveals a Dual Role of AQP4ex Limited to CNS |
title_full_unstemmed | Tissue Distribution of the Readthrough Isoform of AQP4 Reveals a Dual Role of AQP4ex Limited to CNS |
title_short | Tissue Distribution of the Readthrough Isoform of AQP4 Reveals a Dual Role of AQP4ex Limited to CNS |
title_sort | tissue distribution of the readthrough isoform of aqp4 reveals a dual role of aqp4ex limited to cns |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073200/ https://www.ncbi.nlm.nih.gov/pubmed/32102323 http://dx.doi.org/10.3390/ijms21041531 |
work_keys_str_mv | AT palazzoclaudia tissuedistributionofthereadthroughisoformofaqp4revealsadualroleofaqp4exlimitedtocns AT abbresciapasqua tissuedistributionofthereadthroughisoformofaqp4revealsadualroleofaqp4exlimitedtocns AT valenteonofrio tissuedistributionofthereadthroughisoformofaqp4revealsadualroleofaqp4exlimitedtocns AT nicchiagraziapaola tissuedistributionofthereadthroughisoformofaqp4revealsadualroleofaqp4exlimitedtocns AT banitalebishervin tissuedistributionofthereadthroughisoformofaqp4revealsadualroleofaqp4exlimitedtocns AT amirymoghaddammahmood tissuedistributionofthereadthroughisoformofaqp4revealsadualroleofaqp4exlimitedtocns AT trojanomaria tissuedistributionofthereadthroughisoformofaqp4revealsadualroleofaqp4exlimitedtocns AT frigeriantonio tissuedistributionofthereadthroughisoformofaqp4revealsadualroleofaqp4exlimitedtocns |