Journal article

Publication year: 2018

Pages: 6647-6658

Journal: Journal of Biological Chemistry

Volume number: 293

Issue number: 18

Open access status: Hybrid

DOI Link: https://doi.org/10.1074/jbc.RA118.002543

Publisher: Elsevier

Abstract: 
The epithelial sodium channel (ENaC) is a critical regulator of vertebrate electrolyte homeostasis. ENaC is the only constitutively open ion channel in the degenerin/ENaC protein family, and its expression, membrane abundance, and open probability therefore are tightly controlled. The canonical ENaC is composed of three subunits (α, β, and γ), but a fourth δ-subunit may replace α and form atypical δβγ-ENaCs. Using Xenopus laevis as a model, here we found that mRNAs of the α- and δ-subunits are differentially expressed in different tissues and that δ-ENaC predominantly is present in the urogenital tract. Using whole-cell and single-channel electrophysiology of oocytes expressing Xenopus αβγ- or δβγ-ENaC, we demonstrate that the presence of the δ-subunit enhances the amount of current generated by ENaC due to an increased open probability, but also changes current into a transient form. Activity of canonical ENaCs is critically dependent on proteolytic processing of the α- and γ-subunits, and immunoblotting with epitope-tagged ENaC subunits indicated that, unlike α-ENaC, the δ-subunit does not undergo proteolytic maturation by the endogenous protease furin. Furthermore, currents generated by δβγ-ENaC were insensitive to activation by extracellular chymotrypsin, and presence of the δ-subunit prevented cleavage of γ-ENaC at the cell surface. Our findings suggest that subunit composition constitutes an additional level of ENaC regulation, and we propose that the Xenopus δ-ENaC subunit represents a functional example that demonstrates the importance of proteolytic maturation during ENaC evolution.

Harvard Citation style: Wichmann, L., Vowinkel, K., Perniss, A., Manzini, I. and Althaus, M. (2018) Incorporation of the δ-subunit into the epithelial sodium channel (ENaC) generates protease-resistant ENaCs in Xenopus laevis, Journal of Biological Chemistry, 293(18), pp. 6647-6658. https://doi.org/10.1074/jbc.RA118.002543

APA Citation style: Wichmann, L., Vowinkel, K., Perniss, A., Manzini, I., & Althaus, M. (2018). Incorporation of the δ-subunit into the epithelial sodium channel (ENaC) generates protease-resistant ENaCs in Xenopus laevis. Journal of Biological Chemistry. 293(18), 6647-6658. https://doi.org/10.1074/jbc.RA118.002543