Epithelial Sodium Channels Are Activated by Furin-dependent Proteolysis

Rebecca P. Hughey, James B. Bruns, Carol L. Kinlough, Keri L. Harkleroad, Qiusheng Tong, Marcelo D. Carattino, John P. Johnson, James D. Stockand, Thomas R. Kleyman

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Abstract

Epithelial Na+ channels (ENaCs) are activated by extracellular trypsin or by co-expression with channel-activating proteases, although there is no direct evidence that these proteases activate ENaC by cleaving the channel. We previously demonstrated that the α and γ subunits of ENaC are cleaved during maturation near consensus sites for furin cleavage. Using site-specific mutagenesis of channel subunits, ENaC expression in furin-deficient cells, and furin-specific inhibitors, we now report that ENaC cleavage correlates with channel activity. Channel activity in furin-deficient cells was rescued by expression of furin. Our data provide the first example of a vertebrate ion channel that is a substrate for furin and whose activity is dependent on its proteolysis.

Original languageEnglish (US)
Pages (from-to)18111-18114
Number of pages4
JournalJournal of Biological Chemistry
Volume279
Issue number18
DOIs
StatePublished - Apr 30 2004

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Hughey, R. P., Bruns, J. B., Kinlough, C. L., Harkleroad, K. L., Tong, Q., Carattino, M. D., Johnson, J. P., Stockand, J. D., & Kleyman, T. R. (2004). Epithelial Sodium Channels Are Activated by Furin-dependent Proteolysis. Journal of Biological Chemistry, 279(18), 18111-18114. https://doi.org/10.1074/jbc.C400080200