Tissue Distribution of the Readthrough Isoform of AQP4 Reveals a Dual Role of AQP4ex Limited to CNS

Autor: Mahmood Amiry-Moghaddam, Antonio Frigeri, Maria Trojano, Grazia Paola Nicchia, Pasqua Abbrescia, Claudia Palazzo, Onofrio Valente, Shervin Banitalebi
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Gene isoform
Central Nervous System
Central nervous system
Immunoblotting
aquaporin-4
Kidney
Catalysis
Article
Inorganic Chemistry
lcsh:Chemistry
Mice
membrane localization
translational recoding
medicine
Animals
Protein Isoforms
Physical and Theoretical Chemistry
Microscopy
Immunoelectron
Muscle
Skeletal
Molecular Biology
lcsh:QH301-705.5
Spectroscopy
Aquaporin 4
Mice
Knockout
astrocyte endfeet
Chemistry
Organic Chemistry
Translational readthrough
Stomach
Skeletal muscle
Tumor Protein
Translationally-Controlled 1
General Medicine
Immunogold labelling
membrane localization
Computer Science Applications
Cell biology
Trachea
translational recoding
medicine.anatomical_structure
translational readthrough
Gene Expression Regulation
lcsh:Biology (General)
lcsh:QD1-999
Astrocytes
aqp4ex
sense organs
Astrocyte
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 4, p 1531 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 4
ISSN: 1422-0067
Popis: 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.
Databáze: OpenAIRE
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