Malbert-Colas Laurence, Nicolas Gaël, Galand Colette, Lecomte Marie-Christine, Dhermy Didier
Inserm U409 and IFR02, Institut Claude-Bernard, physiologie et pathologie, faculté de médecine Xavier-Bichat, BP 416, 75780 Paris, France.
C R Biol. 2003 Jul;326(7):615-24. doi: 10.1016/s1631-0691(03)00154-9.
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.
由α、β和γ亚基组成的阿米洛利敏感性上皮钠通道（ENaC）的精细调控，对于维持钠平衡和血压至关重要。β-ENaC和γ-ENaC均通过与E3泛素连接酶Nedd4-2相互作用参与负调控。这种相互作用的破坏会导致ENaC活性增加（利德尔综合征）。通过双杂交筛选，我们鉴定出α-ENaC的新潜在伙伴：WWP1（E3泛素连接酶蛋白）、UBC9和TSG101（E2泛素/小泛素相关修饰物缀合酶），并在谷胱甘肽S-转移酶下拉试验中证实了这些相互作用。所有这些伙伴都与蛋白质运输有关，可能参与ENaC活性的调控。
