Identification of new partners of the epithelial sodium channel alpha subunit
Laurence Malbert-Colas1, Gaël Nicolas, Colette Galand
1Inserm U409 and IFR02, Institut Claude-Bernard, physiologie et pathologie, faculté de médecine Xavier-Bichat, BP 416, 75780 Paris, France.
Abstract:
A fine regulation of the amiloride-sensitive Epithelial Sodium Channel (ENaC), made of alpha, beta and gamma subunits, is crucial for maintenance of Na+ balance and blood pressure. Both beta- and gamma-ENaC participate in negative regulation by interacting with Nedd4-2, an E3 ubiquitin-ligase. Disruption of this interaction results in increased ENaC activity (Liddle syndrome). By two-hybrid screenings, we identified new potential partners of alpha-ENaC: WWP1 (E3 ubiquitin-ligase protein), UBC9 and TSG101 (E2 ubiquitin/SUMO-conjugating enzymes) and confirmed these interactions in GST pull-down assays. All these partners are implicated in protein trafficking and could be involved in the regulation of ENaC activity.
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