My laboratory is interested in the regulation of epithelial sodium transport. Studies examine the trafficking, characteristics and post-translational regulation of the epithelial sodium channel, ENaC. Studies of trafficking include evaluation of the role of SNARE proteins in the apical delivery of the channel as well as the role of lipid microdomains in apical targeting. Recent studies have focused on the role of clathrin-mediated endocytosis in retrieval of the channel from the apical membrane, and the molecular partners involved in this process. Studies of recycling of the channel examine the fate decision between recycling and degradation which occurs within the endosomal pathway. The laboratory has advanced a theory of non-coordinate regulation of ENaC trafficking which proposes that there may be differential trafficking of channel subunits within the endosomal pathway. We have a continuing interest in the post-translational regulation of the channel by methylation.
Publications
Butterworth MB, Edinger RS, Ovaa H, Burg D, Johnson JP, Frizzell RA. The deubiquitinating enzyme UCH-L3 regulates the apical membrane recycling of the epithelial sodium channel. J Biol Chem. 2007 Dec 28;282(52):37885-93. Epub 2007 Oct 29.
Hill WG, Butterworth MB, Wang H, Edinger RS, Lebowitz J, Peters KW, Frizzell RA, Johnson JP. The epithelial sodium channel (ENaC) traffics to apical membrane in lipid rafts in mouse cortical collecting duct cells. J Biol Chem. 2007 Dec 28;282(52):37402-11. Epub 2007 Oct 10.
Weixel KM, Edinger RS, Kester L, Guerriero CJ, Wang H, Fang L, Kleyman TR, Welling PA, Weisz OA, Johnson JP. Phosphatidylinositol 4-phosphate 5-kinase reduces cell surface expression of the epithelial sodium channel (ENaC) in cultured collecting duct cells. J Biol Chem. 2007 Dec 14;282(50):36534-42. Epub 2007 Oct 16.
Edinger RS, Yospin J, Perry C, Kleyman TR, Johnson JP. Regulation of epithelial Na+ channels (ENaC) by methylation: a novel methyltransferase stimulates ENaC activity. J Biol Chem. 2006 Apr 7;281(14):9110-7. Epub 2006 Feb 8.
Wang H, Traub LM, Weixel KM, Hawryluk MJ, Shah N, Edinger RS, Perry CJ, Kester L, Butterworth MB, Peters KW, Kleyman TR, Frizzell RA, Johnson JP. Clathrin-mediated endocytosis of the epithelial sodium channel. Role of epsin. J Biol Chem. 2006 May 19;281(20):14129-35. Epub 2006 Mar 30.