Journal article
Minireview: regulation of epithelial Na+ channel trafficking
Endocrinology (Philadelphia), Vol.146(12), pp.5079-5085
12/2005
DOI: 10.1210/en.2005-0894
PMID: 16150899
Abstract
The epithelial Na(+) channel (ENaC) is a pathway for Na(+) transport across epithelia, including the kidney collecting duct, lung, and distal colon. ENaC is critical for Na(+) homeostasis and blood pressure control; defects in ENaC function and regulation are responsible for inherited forms of hypertension and hypotension and may contribute to the pathogenesis of cystic fibrosis and other lung diseases. An emerging theme is that epithelial Na(+) transport is regulated in large part through trafficking mechanisms that control ENaC expression at the cell surface. ENaC trafficking is regulated at multiple steps. Delivery of channels to the cell surface is regulated by aldosterone (and corticosteroids) and vasopressin, which increase ENaC synthesis and exocytosis, respectively. Conversely, endocytosis and degradation is controlled by a sequence located in the C terminus of alpha, beta, and gammaENaC (PPPXYXXL). This sequence functions as an endocytosis motif and as a binding site for Nedd4-2, an E3 ubiquitin protein ligase that targets ENaC for degradation. Mutations that delete or disrupt this motif cause accumulation of channels at the cell surface, resulting in Liddle's syndrome, an inherited form of hypertension. Nedd4-2 is a central convergence point for ENaC regulation by aldosterone and vasopressin; both induce phosphorylation of a common set of three Nedd4-2 residues, which blocks Nedd4-2 binding to ENaC. Thus, aldosterone and vasopressin regulate epithelial Na(+) transport in part by altering ENaC trafficking to and from the cell surface.
Details
- Title: Subtitle
- Minireview: regulation of epithelial Na+ channel trafficking
- Creators
- Peter M Snyder - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, 52242, USA. peter-snyder@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Endocrinology (Philadelphia), Vol.146(12), pp.5079-5085
- DOI
- 10.1210/en.2005-0894
- PMID
- 16150899
- NLM abbreviation
- Endocrinology
- ISSN
- 0013-7227
- eISSN
- 1945-7170
- Publisher
- United States
- Grant note
- HL58812 / NHLBI NIH HHS HL72256 / NHLBI NIH HHS DK52617 / NIDDK NIH HHS HL55006 / NHLBI NIH HHS
- Language
- English
- Date published
- 12/2005
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Medicine Administration; Internal Medicine
- Record Identifier
- 9984025322802771
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