A novel human aquaporin-4 splice variant exhibits a dominant-negative activity: a new mechanism to regulate water permeability.

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_8A88156A6653
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A novel human aquaporin-4 splice variant exhibits a dominant-negative activity: a new mechanism to regulate water permeability.
Périodique
Molecular Biology of the Cell
Auteur(s)
De Bellis M., Pisani F., Mola M.G., Basco D., Catalano F., Nicchia G.P., Svelto M., Frigeri A.
ISSN
1939-4586 (Electronic)
ISSN-L
1059-1524
Statut éditorial
Publié
Date de publication
2014
Volume
25
Numéro
4
Pages
470-480
Langue
anglais
Résumé
Two major isoforms of aquaporin-4 (AQP4) have been described in human tissue. Here we report the identification and functional analysis of an alternatively spliced transcript of human AQP4, AQP4-Δ4, that lacks exon 4. In transfected cells AQP4-Δ4 is mainly retained in the endoplasmic reticulum and shows no water transport properties. When AQP4-Δ4 is transfected into cells stably expressing functional AQP4, the surface expression of the full-length protein is reduced. Furthermore, the water transport activity of the cotransfectants is diminished in comparison to transfectants expressing only AQP4. The observed down-regulation of both the expression and water channel activity of AQP4 is likely to originate from a dominant-negative effect caused by heterodimerization between AQP4 and AQP4-Δ4, which was detected in coimmunoprecipitation studies. In skeletal muscles, AQP4-Δ4 mRNA expression inversely correlates with the level of AQP4 protein and is physiologically associated with different types of skeletal muscles. The expression of AQP4-Δ4 may represent a new regulatory mechanism through which the cell-surface expression and therefore the activity of AQP4 can be physiologically modulated.
Pubmed
Web of science
Open Access
Oui
Création de la notice
04/09/2014 8:37
Dernière modification de la notice
20/08/2019 14:49
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