Premium
Multiple Residues in the Distal C‐terminus of the Alpha Subunit Have Roles in Modulating ENaC Activity
Author(s) -
Mueller Gunhild M.,
Yan Wusheng,
Copelovitch Lawrence,
Jarman Susan,
Tolino Michael A.,
Kleyman Thomas R.,
Rubenstein Ronald C.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1041.15
Subject(s) - epithelial sodium channel , xenopus , protein subunit , microbiology and biotechnology , chemistry , population , biology , biochemistry , gene , sodium , medicine , environmental health , organic chemistry
Epithelial sodium channels (ENaC) are critically important in the regulation of ion and fluid balance in both renal and respiratory epithelia. ENaC functional polymorphisms may contribute to alterations in blood pressure in the general population. We previously showed that the A663T polymorphism in the C‐terminus of the α‐subunit increases ENaC functional and surface expression in Xenopus oocytes. We examined whether mutations of residues adjacent to A663 also influenced channel activity by performing scanning Ala mutagenesis of the 10 residues flanking αT663. Interestingly, only the G667A increased ENaC currents compared to wild type. This residue is not conserved across species. In contrast, C664 is conserved in the human, mouse and rat α subunit. The C664M mutation decreased the functional expression of αT663 ENaC to a level similar to that of αA663. The C664M mutation had no effect on the functional expression of αA663 ENaC. The decrease in αT663/C664M ENaC functional expression correlated with decreased expression of β ENaC at the oocyte surface, but not in whole oocyte β ENaC expression, suggesting that α T663/C664M ENaC had altered intracellular trafficking relative to αT663 ENaC. Our results suggest that multiple residues in the distal part of the cytoplasmic C‐terminus have roles in modulating channel activity.