Membrane Biology
Accessibility of ENaC extracellular domain central core residues
The epithelial Na+ channel (ENaC)/degenerin family has a similar extracellular architecture, where specific regulatory factors interact and alter channel gating behavior. The extracellular palm domain serves as a key link to the channel pore. In this study, we used cysteine-scanning mutagenesis to assess the functional effects of Cys-modifying reagents on palm domain β10 strand residues in mouse ENaC. Of the 13 ENaC α subunit mutants with Cys substitutions examined, only mutants at sites in the proximal region of β10 exhibited changes in channel activity in response to methanethiosulfonate reagents.Functional Roles of Clusters of Hydrophobic and Polar Residues in the Epithelial Na+ Channel Knuckle Domain
Background: There are regulatory interactions between ENaC and extracellular factors.Results: Mutations of multiple α subunit knuckle residues activate ENaC by suppressing the inhibitory effect of Na+. Channels lacking the β or γ subunit knuckle have processing defects.Conclusion: Interactions between the α subunit knuckle and palm/finger domains regulate ENaC.Significance: Intrasubunit domain-domain interactions have important regulatory roles.
