Härteis S, Krüger B, Korbmacher C, Rauh R (2009)
Publication Language: English
Publication Type: Journal article, Original article
Publication year: 2009
Publisher: American Society for Biochemistry and Molecular Biology
Book Volume: 284
Pages Range: 29024-29040
Journal Issue: 42
The epithelial sodium channel (ENaC) is probably a heterotrimer with three well characterized subunits (αβγ). In humans an additional δ-subunit (δ-hENaC) exists but little is known about its function. Using the Xenopus laevis oocyte expression system, we compared the functional properties of αβγ- and δβγ-hENaC and investigated whether δβγ-hENaC can be proteolytically activated. The amiloride-sensitive ENaC whole-cell current (ΔIami) was about 11-fold larger in oocytes expressing δβγ-hENaC than in oocytes expressing αβγ-hENaC. The 2-fold larger single-channel Na+ conductance of δβγ-hENaC cannot explain this difference. Using a chemiluminescence assay, we demonstrated that an increased channel surface expression is also not the cause. Thus, overall channel activity of δβγ-hENaC must be higher than that of αβγ-hENaC. Experiments exploiting the properties of the known βS520C mutant ENaC confirmed this conclusion. Moreover, chymotrypsin had a reduced stimulatory effect on δβγ-hENaC whole-cell currents compared with its effect on αβγ-hENaC whole-cell currents (2-fold versus 5-fold). This suggests that the cell surface pool of so-called near-silent channels that can be proteolytically activated is smaller for δβγ-hENaC than for αβγ-hENaC. Proteolytic activation of δβγ-hENaC was associated with the appearance of a Δ-hENaC cleavage product at the cell surface. Finally, we demonstrated that a short inhibitory 13-mer peptide corresponding to a region of the extracellular loop of human α-ENaC inhibited ΔIami in oocytes expressing αβγ-hENaC but not in those expressing δβγ-hENaC. We conclude that the δ-subunit of ENaC alters proteolytic channel activation and enhances base-line channel activity. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
APA:
Härteis, S., Krüger, B., Korbmacher, C., & Rauh, R. (2009). The δ-subunit of the epithelial sodium channel (ENaC) enhances channel activity and alters proteolytic ENaC activation. Journal of Biological Chemistry, 284(42), 29024-29040. https://doi.org/10.1074/jbc.M109.018945
MLA:
Härteis, Silke, et al. "The δ-subunit of the epithelial sodium channel (ENaC) enhances channel activity and alters proteolytic ENaC activation." Journal of Biological Chemistry 284.42 (2009): 29024-29040.
BibTeX: Download