5' heterogeneity in epithelial sodium channel alpha-subunit mRNA leads to distinct NH2-terminal variant proteins

Christie P Thomas; Scott Auerbach; John B Stokes; Kenneth A Volk

doi:10.1152/ajpcell.1998.274.5.C1312

Back

5' heterogeneity in epithelial sodium channel alpha-subunit mRNA leads to distinct NH2-terminal variant proteins

Journal article

Open access

Peer reviewed

5' heterogeneity in epithelial sodium channel alpha-subunit mRNA leads to distinct NH2-terminal variant proteins

Christie P Thomas, Scott Auerbach, John B Stokes and Kenneth A Volk

The American journal of physiology, Vol.274(5), pp.C1312-1323

05/1998

DOI: 10.1152/ajpcell.1998.274.5.C1312

PMID: 9612219

Files and links (1)

url

https://doi.org/10.1152/ajpcell.1998.274.5.C1312View

Published (Version of record) Open Access

Abstract

The amiloride-sensitive epithelial sodium channel (ENaC) is composed of three subunits: alpha, beta, and gamma. The human alpha-ENaC subunit is expressed as at least two transcripts (N. Voilley, E. Lingueglia, G. Champigny, M. G. Mattei, R. Waldmann, M. Lazdunski, and P. Barbry. Proc. Natl. Acad. Sci. USA 91: 247-251, 1994). To determine the origin of these transcripts, we characterized the 5' end of the alpha-ENaC gene. Four transcripts that differ at their first exon were identified. Exon 1A splices to exon 2 to form the 5' end of alpha-ENaC1, whereas exon 1B arises separately and continues into exon 2 to form alpha-ENaC2. Other variant mRNAs, alpha-ENaC3 and alpha-ENaC4, are formed by activating 5' splice sites within exon 1B. Although alpha-ENaC3 and -4 did not change the open reading frame for alpha-ENaC, alpha-ENaC2 contains upstream ATGs that add 59 amino acids to the previous (alpha-ENaC1) protein. To address the significance of these isoforms, both proteins were expressed in Xenopus oocytes. The cRNA for each alpha-ENaC transcript when combined with beta- and gamma-ENaC cRNA reconstituted a low-conductance ion channel with amiloride-sensitive currents of similar characteristics. We have thus identified variant alpha-ENaC mRNAs that lead to functional ENaC peptides.

Amino Acid Sequence

Oocytes - metabolism

Humans

RNA, Messenger - genetics

Xenopus laevis

Molecular Sequence Data

Electric Conductivity

Sodium Channels - physiology

Isomerism

Epithelial Sodium Channels

Patch-Clamp Techniques

Animals

Base Sequence

Sodium Channels - metabolism

Female

Genetic Variation - genetics

Sodium Channels - genetics

Tumor Cells, Cultured

Details

Title: Subtitle: 5' heterogeneity in epithelial sodium channel alpha-subunit mRNA leads to distinct NH2-terminal variant proteins
Creators: Christie P Thomas - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USA
Scott Auerbach
John B Stokes
Kenneth A Volk
Resource Type: Journal article
Publication Details: The American journal of physiology, Vol.274(5), pp.C1312-1323
Publisher: United States
DOI: 10.1152/ajpcell.1998.274.5.C1312
PMID: 9612219
ISSN: 0002-9513
eISSN: 2163-5773
Grant note: DK-52617 / NIDDK NIH HHS
Language: English
Date published: 05/1998
Academic Unit: Stead Family Department of Pediatrics; Obstetrics and Gynecology; Nephrology; Internal Medicine
Record Identifier: 9983986259402771

Metrics

30 Record Views

51 Times Cited - Web of Science

See more details