Regulation of the delta and alpha epithelial sodium channel (ENaC) by ubiquitination and Nedd8

• DOI: 10.1002/jcp.24390
• Publication Date: 2013-04-15T14:13:26Z
• Authors: Kevin Ly; C. Joy McIntosh; Wolfgang Biasio; Yongfeng Liu; Ying Ke; Diane R. Olson; John H. Miller; Rachel Page; Peter M. Snyder; Fiona J. McDonald
• Keywords: Epithelial sodium channel; Amiloride; NEDD4

The δ epithelial sodium channel (δENaC) is a proton-activated, sodium-selective, amiloride-sensitive ion in the ENaC/degenerin family of channels involved blood pressure regulation and mechanosensation. Other ENaC members are subject to ubiquitin modification leading internalization from cell surface, degradation channel. Here, we show that δENaC also modified by on three intracellular lysine residues. Absence these lysines abolished increased surface levels δENaC. Although HECT-domain ligase Nedd4-2 reduced current generated δβγENaC-containing channels, does not contain binding site for Nedd4-2; therefore, this effect probably mediated βγENaC subunits. Nedd8, ubiquitin-like protein regulates RING-domain E3 ligases, promoted ubiquitination, decreased both populations, δβγENaC short circuit (Isc -amiloride) mammalian epithelium. Nedd8 α- γENaC pools, αβγENaC Isc -amiloride. Conversely, XIAP, single subunit RING ligase, ubiquitinated δENaC, pool Therefore δ- α - function may be influenced ligases.