Journal article
Acetylation Stimulates the Epithelial Sodium Channel by Reducing Its Ubiquitination and Degradation
The Journal of biological chemistry, Vol.290(20), pp.12497-12503
05/15/2015
DOI: 10.1074/jbc.M114.635540
PMCID: PMC4432271
PMID: 25787079
Abstract
The epithelial Na+ channel (ENaC) functions as a pathway for Na+ absorption in the kidney and lung, where it is crucial for Na+ homeostasis and blood pressure regulation. ENaC is regulated in part through signaling pathways that control the ubiquitination state of ENaC lysines. A defect in ubiquitination causes Liddle syndrome, an inherited form of hypertension. Here we determined that alpha-, beta-, and gamma ENaC are also substrates for lysine acetylation. Trichostatin A (TSA), a histone deacetylase inhibitor, enhanced ENaC acetylation and increased ENaC abundance in the total cell lysate and at the cell surface. Moreover, TSA increased ENaC current in Fischer rat thyroid and kidney collecting duct epithelia. We found that HDAC7 is expressed in the kidney collecting duct, supporting a potential role for this histone deacetylase in ENaC regulation. HDAC7 overexpression reduced ENaC abundance and ENaC current, whereas ENaC abundance and current were increased by silencing of HDAC7. ENaC and HDAC7 form a complex, as detected by coimmunoprecipitation. We observed a reciprocal relationship between acetylation and ubiquitination; TSA reduced ENaC ubiquitination, whereas HDAC7 increased ubiquitination. By reducing ENaC ubiquitination, TSA decreased the rate of ENaC degradation. Thus, acetylation increases epithelial Na+ absorption by antagonizing ENaC ubiquitination. This stabilizes ENaC, and hence, increases its abundance at the cell surface.
Details
- Title: Subtitle
- Acetylation Stimulates the Epithelial Sodium Channel by Reducing Its Ubiquitination and Degradation
- Creators
- Phillip L. Butler - Roy J. and Lucille A. Carver College of MedicineAlexander Staruschenko - Medical College of WisconsinPeter M. Snyder - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.290(20), pp.12497-12503
- DOI
- 10.1074/jbc.M114.635540
- PMID
- 25787079
- PMCID
- PMC4432271
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Amer Soc Biochemistry Molecular Biology Inc
- Number of pages
- 7
- Grant note
- HL058812; HL072256; HL108880 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01HL058812 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) I01BX001862 / Veterans Affairs; US Department of Veterans Affairs BX001862 / Department of Veterans Affairs Biomedical Laboratory Research and Development Service Grant; US Department of Veterans Affairs American Heart Association Postdoctoral Research Fellowship; American Heart Association
- Language
- English
- Date published
- 05/15/2015
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Medicine Administration; Internal Medicine
- Record Identifier
- 9984297608602771
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