Logo image
Back
Nedd4‐2 Isoforms Polyubiquitinate Individual ENaC Subunits and Reduce Surface Expression of the Sodium Channel
Abstract   Open access   Peer reviewed

Nedd4‐2 Isoforms Polyubiquitinate Individual ENaC Subunits and Reduce Surface Expression of the Sodium Channel

Nandita Sudhanshu Raikwar and Christie P Thomas
The FASEB journal, Vol.21(6), pp.A956-A956
2007
DOI: 10.1096/fasebj.21.6.A956
url
https://doi.org/10.1096/fasebj.21.6.a956View
Published (Version of record) Open Access

Abstract

Nedd4‐2 when overexpressed in M‐1 collecting duct epithelia reduces benzamil‐sensitive Na+ transport. α, β, & γ ENaC subunits contain a PY motif, which interacts with WW domain of the ubiquitin ligase Nedd4‐2 resulting in down regulation of ENaC which is thought to occur via enhanced ubiquitination and internalization of the assembled heterotrimeric channel complex. We investigated cell‐surface expression and ubiquitination of tagged ENaC subunits in HEK 293 by surface biotinylation and immunoprecipitation. α, β and γ ENaC subunits when expressed alone or together are polyubiquitinated which is enhanced by Nedd4‐2 suggesting that each subunit is a target for Nedd4‐2 mediated ubiquitination. αENaC when transfected alone or with β and γENaC is expressed at the cell surface and this membrane expression is dramatically reduced by co‐expression with each of three human Nedd4‐2 isoforms. Our findings suggest that αENaC is present at the cell surface even when expressed alone and that each of the ENaC subunits can interact with Nedd4‐2 and be ubiquitinated as single subunits or as a complex. Furthermore the cell surface expression of ENaC is reduced by Nedd4‐2 which correlates with enhanced ubiquitination of these subunits and the reduction in Na+ transport seen in collecting duct cells.

Details

Metrics

11 Record Views
Logo image