Premium
Translational readthrough generates new astrocyte AQP4 isoforms that modulate supramolecular clustering, glial endfeet localization, and water transport
Author(s) -
De Bellis Manuela,
Pisani Francesco,
Mola Maria Grazia,
Rosito Stefania,
Simone Laura,
Buccoliero Cinzia,
Trojano Maria,
Nicchia Grazia Paola,
Svelto Maria,
Frigeri Antonio
Publication year - 2017
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23126
Subject(s) - biology , gene isoform , astrocyte , microbiology and biotechnology , phosphorylation , aquaporin 4 , aquaporin , context (archaeology) , neuroscience , central nervous system , biochemistry , gene , paleontology
Regulation of water homeostasis is a central feature of central nervous system pathophysiology. In this context, several lines of evidence suggest a crucial role for the water channel aquaporin‐4 (AQP4) and its plasma membrane supramolecular organization as the key element. Here, we demonstrate the expression in tissues of additional isoforms of AQP4 characterized by a C‐terminal extension generated by programmed translational readthrough. These extended isoforms (AQP4ex) display a perivascular polarization and expression in dystrophin‐dependent pools. AQP4ex reduces supramolecular clustering tendency and allows AQP4 interactions with syntrophin. Furthermore, site‐directed mutagenesis of two serines in the extended C‐terminus of AQP4ex showed potential regulation of water permeability by phosphorylation. Finally, AQP4ex expression can be positively modulated by gentamicin treatment, demonstrating the possibility of regulating the AQP4 translational readthrough frequency. This novel regulatory mechanism could have important pathophysiological implications for conditions in which alternations have been reported in AQP4 structure.