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Molecular taxis: impact of candidate genes on epithelial sodium channel function (997.7)
Author(s) -
Hall Jeffrey,
Booth Rachell
Publication year - 2014
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.28.1_supplement.997.7
Subject(s) - epithelial sodium channel , microbiology and biotechnology , biology , transmembrane protein , endoplasmic reticulum , ubiquitin , mutant , gene , chemistry , genetics , sodium , receptor , organic chemistry
The epithelial sodium channel (ENaC) is a heterotrimeric transmembrane protein located in the apical membrane of the renal epithelium. This highly selective ion channel plays an important role in the homeostasis of both electrolyte and extracellular fluid levels in mammalian systems. While a number of molecular pathways responsible for regulation of ENaC‐such as those through SGK1‐dependent activation, Nedd‐4 ubiquitination preceding proteosomal degradation, and others‐the entirety of the ENaC regulatory pathway is not known. Our lab has expressed homotrimeric αENaC channels in yeast mutants taken from a yeast deletion library, each chosen due to general roles in endosomal trafficking and membrane localization. In order to assess the impact of genomic mutations in the presence of exogenous sodium chloride, a serial dilution growth assay was performed and mutants exhibiting phenotypic variations from wild type were identified. Specifically, three deletion strains were observed to have significant differences in growth patterns, as compared to control phenotypes. The HRD1 and SSM4 genes encode ubiquitin‐protein ligases responsible for degradation of misfolded proteins associated with the endoplasmic reticulum (ER). The SCJ1 gene codes for a chaperone protein involved in mediating maturation of proteins in the ER. Further characterization of candidate gene interactions with ENaC will provide greater insight into the regulation of an important player in sodium homeostasis. Grant Funding Source : Supported by NIH R15 GM86798 (R. Booth & W. David) and Welch Foundation Departmental Grant AI‐0045