Journal article
Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na+ channel
American journal of physiology. Renal physiology, Vol.283(3), pp.F431-F436
09/01/2002
DOI: 10.1152/ajprenal.00080.2002
PMID: 12167593
Abstract
The epithelial Na+ channel (ENaC) is a critical component of the pathway maintaining salt and water balance. The channel is regulated by members of the Nedd4 family of ubiquitin-protein ligases, which bind to channel subunits and catalyze channel internalization and degradation. ENaC mutations that abolish this interaction cause Liddle's syndrome, a genetic form of hypertension. Here, we test the hypothesis that WW domain-containing protein 2 (WWP2), a member of the Nedd4 family of ubiquitin-protein ligases, is a candidate to regulate ENaC. Consistent with this hypothesis, we found that WWP2 is expressed in epithelial tissues that express ENaC, as well as in a wide variety of other tissues. WWP2 contains four WW domains, three of which bound differentially to ENaC subunits. In contrast, all four human Nedd4–2 WW domains bound to ENaC. WWP2 inhibited ENaC when coexpressed in epithelia, requiring a direct interaction between the proteins; mutation of the ENaC PY motifs abolished inhibition. Thus expression, binding, and functional data all suggest that WWP2 is a candidate to regulate ENaC-mediated Na+ transport in epithelia.
Details
- Title: Subtitle
- Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na+ channel
- Creators
- Fiona J McDonald - Department of Physiology, University of Otago, Dunedin 9100, New Zealand; andAndrea H Western - Department of Physiology, University of Otago, Dunedin 9100, New Zealand; andJohn D McNeil - Department of Physiology, University of Otago, Dunedin 9100, New Zealand; andBrittany C Thomas - Departments of Internal Medicine and of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242Diane R Olson - Departments of Internal Medicine and of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242Peter M Snyder - Departments of Internal Medicine and of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Renal physiology, Vol.283(3), pp.F431-F436
- DOI
- 10.1152/ajprenal.00080.2002
- PMID
- 12167593
- ISSN
- 1931-857X
- eISSN
- 1522-1466
- Language
- English
- Date published
- 09/01/2002
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Medicine Administration; Internal Medicine
- Record Identifier
- 9984025587702771
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