Nedd4-2 Catalyzes Ubiquitination and Degradation of Cell Surface ENaC

摘要: Epithelial Na+ absorption is regulated by Nedd4-2, an E3 ubiquitin-protein ligase that reduces expression of the epithelial channel ENaC at cell surface. Defects in this regulation cause Liddle syndrome, inherited form hypertension. Previous work found Nedd4-2 binds to via PY motifs located C termini α-, β-, and γENaC. However, little known about mechanism which regulates surface expression. Here we catalyzes ubiquitination γENaC; overexpression increased ubiquitination, whereas silencing decreased ubiquitination. Although both mono/oligoubiquitinated multiubiquitinated forms ENaC, monoubiquitination was sufficient for reduce current. Ubiquitination disrupted syndrome-associated mutations or mutation catalytic HECT domain Nedd4-2. Several findings suggest interaction between localized First, bound a population Second, catalyzed ENaC. Third, selectively reduced but did not alter quantity immature biosynthetic pathway. Finally, induced degradation pool Together, data model ubiquitinates surface, targets degradation, thus, transport.