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• W2041879427 abstract "Proteolytic enzymes cleave the epithelial Na + channel (ENaC) at several positions releasing, in part, the NH 2 terminus of the γ-subunit. Cleavage increases ENaC activity by increasing open probability; however, the role of polypeptides cleaved from the channel core remains unclear. We find that the cytosolic NH 2 terminus of γ-ENaC unexpectedly targets to the nucleus being particularly strong in nucleoli. In contrast, the cytosolic COOH terminus targets to the cytoplasm and plasma membrane in a manner similar to full-length subunits. Targeting of the cytosolic NH 2 terminus of γ-ENaC to the nucleus has functional consequences for coexpression of eGFP-fusion proteins containing this segment of the channel, but not the COOH terminus, decrease ENaC activity in a dose-dependent manner. The mechanism of this negative regulation is associated with a decrease in the functional half-life of ENaC at the plasma membrane. Inspection of the primary amino acid sequence of γ-ENaC reveals possible nuclear localization signals (NLS) conserved at the extreme NH 2 terminus and just preceding the first transmembrane domain. Disruption of the putative NLS preceding the first transmembrane domain in γ-ENaC but not that at the extreme NH 2 terminus abolishes both targeting to the nucleus and negative regulation of ENaC activity. These findings are consistent with the release of the NH 2 terminus of γ-ENaC following cleavage being functionally important for signaling to the nucleus in a manner similar to Notch signaling and release of the cytosolic COOH-terminal tail of polycystin-1." @default.
• W2041879427 created "2016-06-24" @default.
• W2041879427 creator A5016388201 @default.
• W2041879427 creator A5086554315 @default.
• W2041879427 date "2010-05-01" @default.
• W2041879427 modified "2023-09-23" @default.
• W2041879427 title "Activation of a latent nuclear localization signal in the NH2 terminus of γ-ENaC initiates feedback regulation of channel activity" @default.
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• W2041879427 doi "https://doi.org/10.1152/ajprenal.00600.2009" @default.
• W2041879427 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2867411" @default.
• W2041879427 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20147367" @default.
• W2041879427 hasPublicationYear "2010" @default.
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