Membrane Biology
Regulation of the epithelial Na+ channel by paraoxonase-2
Paraoxonase-2 (PON-2) is a membrane-bound lactonase with unique anti-oxidative and anti-atherosclerotic properties. PON-2 shares key structural elements with MEC-6, an endoplasmic reticulum–resident molecular chaperone in Caenorhabditis elegans. MEC-6 modulates the expression of a mechanotransductive ion channel comprising MEC-4 and MEC-10 in touch-receptor neurons. Because pon-2 mRNA resides in multiple rat nephron segments, including the aldosterone-sensitive distal nephron where the epithelial Na+ channel (ENaC) is expressed, we hypothesized that PON-2 would similarly regulate ENaC expression.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.
