Abstract
Liddle’s syndrome mutations increase proteolytic cleavage of ENaC
The FASEB journal, Vol.20(4), pp.A794-A795
03/2006
DOI: 10.1096/fasebj.20.4.A794-d
Abstract
□Liddle’s syndrome mutations increase epithelial Na transport by increasing ENaC surface expression. Previous work suggested that Liddle’s mutations might also alter ENaC gating, although the mechanism has not been identified. Recent work indicates that ENaC is proteolytically cleaved by furin during transport to the cell surface, which activates the channel. We hypothesized that Liddle’s syndrome mutations might alter ENaC gating by altering its cleavage. We found that a Liddle’s syndrome mutation in βENaC (R566X) increased expression of αENaC at the cell surface. Interestingly, there was a greater increase in surface expression of the cleaved form than the non‐cleaved form of αENaC. A Liddle’s syndrome mutation in γENaC had a similar effect. Moreover, the cleaved form of γENaC was also selectively increased at the cell surface by a Liddle’s syndrome mutation. As an additional approach, we expressed wild‐type and Liddle’s mutant channels in FRT epithelia, and quantitated ENaC current before and after treatment with trypsin (to activate non‐cleaved channels). We found that Liddle’s syndrome mutations decreased trypsin‐activation of ENaC. Together, the results indicate that Liddle’s syndrome mutations selectively increase expression of cleaved ENaC channels at the cell surface. This may provide a novel mechanistic explanation for the previous observation that Liddle’s syndrome mutations may alter ENaC gating.
Details
- Title: Subtitle
- Liddle’s syndrome mutations increase proteolytic cleavage of ENaC
- Creators
- Kristin K Knight - University of IowaDiane R Olson - University of IowaRuifeng Zhou - University of IowaPeter M Snyder - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.20(4), pp.A794-A795
- Publisher
- Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.20.4.A794-d
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 03/2006
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine; Medicine Administration
- Record Identifier
- 9984303004102771
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