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Interactions between Subunits of the Human Epithelial Sodium Channel
Journal article   Open access   Peer reviewed

Interactions between Subunits of the Human Epithelial Sodium Channel

Christopher M Adams, Peter M Snyder and Michael J Welsh
The Journal of biological chemistry, Vol.272(43), pp.27295-27300
10/24/1997
DOI: 10.1074/jbc.272.43.27295
PMID: 9341177
url
https://doi.org/10.1074/jbc.272.43.27295View
Published (Version of record) Open Access

Abstract

The human epithelial sodium channel (hENaC) mediates Na+ transport across the apical membrane of epithelia, and mutations in hENaC result in hypertensive and salt-wasting diseases. In heterologous expression systems, maximal hENaC function requires co-expression of three homologous proteins, the alpha, beta, and gammahENaC subunits, suggesting that hENaC subunits interact to form a multimeric channel complex. Using a co-immunoprecipitation assay, we found that hENaC subunits associated tightly to form homo- and heteromeric complexes and that the association between subunits occurred early in channel biosynthesis. Deletion analysis of gammahENaC revealed that the N terminus was sufficient but not necessary for co-precipitation of alphahENaC, and that both the N terminus and the second transmembrane segment (M2) were required for gamma subunit function. The biochemical studies were supported by functional studies. Co-expression of gamma subunits lacking M2 with full-length hENaC subunits revealed an inhibitory effect on hENaC channel function that appeared to be mediated by the cytoplasmic N terminus of gamma, and was consistent with the assembly of nonfunctional subunits into the channel complex. We conclude that the N terminus of gammahENaC is involved in channel assembly.

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