J Biol Chem 2007 Mar 02;2829:6153-60. doi: 10.1074/jbc.M610636200.

Epithelial Na+ channels are fully activated by furin- and prostasin-dependent release of an inhibitory peptide from the gamma-subunit.

???displayArticle.abstract???
Epithelial sodium channels (ENaC) are expressed in the apical membrane of high resistance Na(+) transporting epithelia and have a key role in regulating extracellular fluid volume and the volume of airway surface liquids. Maturation and activation of ENaC subunits involves furin-dependent cleavage of the ectodomain at two sites in the alpha subunit and at a single site within the gamma subunit. We now report that the serine protease prostasin further activates ENaC by inducing cleavage of the gamma subunit at a site distal to the furin cleavage site. Dual cleavage of the gamma subunit is predicted to release a 43-amino acid peptide. Channels with a gamma subunit lacking this 43-residue tract have increased activity due to a high open probability. A synthetic peptide corresponding to the fragment cleaved from the gamma subunit is a reversible inhibitor of endogenous ENaCs in mouse cortical-collecting duct cells and in primary cultures of human airway epithelial cells. Our results suggest that multiple proteases cleave ENaC gamma subunits to fully activate the channel.

???displayArticle.pubmedLink??? 17199078
???displayArticle.link??? J Biol Chem
???displayArticle.grants??? [+]

Species referenced: Xenopus
Genes referenced: furin prss8 prss8l.1