Journal article
Effect of subunit composition and Liddle’s syndrome mutations on biosynthesis of ENaC
American Journal of Physiology: Cell Physiology, Vol.276(6), pp.C1346-C1351
06/01/1999
DOI: 10.1152/ajpcell.1999.276.6.C1346
PMID: 10362597
Abstract
The epithelial Na+ channel (ENaC) is comprised of three homologous subunits: α, β, and γ, all of which are required for formation of the fully functional channel. This channel is responsible for salt reabsorption in the kidney, the airway, and the large bowel. Mutations in ENaC can cause human disease by increasing channel function in Liddle’s syndrome, a form of hereditary hypertension, or by decreasing channel function in pseudohypoaldosteronism type I, a salt-wasting disease of infancy. We previously showed that ENaC is expressed on the cell surface as a minimally glycosylated, Triton-insoluble protein. In the present study we found that ENaC existed initially as a Triton-soluble protein that contained high-mannose glycosylation, presumably in the endoplasmic reticulum. This form of the protein disappeared as the Triton-insoluble, minimally glycosylated form became the more prevalent species. In pulse-chase studies of individually expressed subunits, we found that the Triton-soluble form of β-ENaC accumulated initially, whereas the Triton-soluble form of α-ENaC decreased throughout the time course. However, when all three subunits were coexpressed, the α- and β-subunits showed a similar pattern. The complex became Triton insoluble at some point after the endoplasmic reticulum, as incubation at 15°C blocked the conversion to the insoluble form. Deletion of the carboxy-terminal tail of β-ENaC causes Liddle’s syndrome. This mutation increased the amount of newly synthesized Triton-insoluble ENaC heteromultimers but did not affect the half-life of insoluble protein. Therefore, subunit composition and mutations in individual subunits can influence biosynthesis of the ENaC complex.
Details
- Title: Subtitle
- Effect of subunit composition and Liddle’s syndrome mutations on biosynthesis of ENaC
- Creators
- Lawrence S Prince - Howard Hughes Medical Institute, Departments of Pediatrics, Internal Medicine, and Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242Michael J Welsh - Howard Hughes Medical Institute, Departments of Pediatrics, Internal Medicine, and Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- American Journal of Physiology: Cell Physiology, Vol.276(6), pp.C1346-C1351
- DOI
- 10.1152/ajpcell.1999.276.6.C1346
- PMID
- 10362597
- NLM abbreviation
- Am J Physiol Cell Physiol
- ISSN
- 0363-6143
- eISSN
- 1522-1563
- Language
- English
- Date published
- 06/01/1999
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020849902771
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