| First Author | Bruns JB | Year | 2007 |
| Journal | J Biol Chem | Volume | 282 |
| Issue | 9 | Pages | 6153-60 |
| PubMed ID | 17199078 | Mgi Jnum | J:120890 |
| Mgi Id | MGI:3708212 | Doi | 10.1074/jbc.M610636200 |
| Citation | Bruns JB, et al. (2007) Epithelial Na+ channels are fully activated by furin- and prostasin-dependent release of an inhibitory peptide from the gamma-subunit. J Biol Chem 282(9):6153-60 |
| abstractText | 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. |
