Multiple epithelial Na+ channel domains participate in subunit assembly

American Journal of Physiology. Renal Physiology
James B BrunsThomas R Kleyman

Abstract

Epithelial sodium channels (ENaCs) are composed of three structurally related subunits that form a tetrameric channel. The Xenopus laevis oocyte expression system was used to identify regions within the ENaC alpha-subunit that confer a dominant negative phenotype on functional expression of alphabetagamma-ENaC to define domains that have a role in subunit-subunit interactions. Coexpression of full-length mouse alphabetagamma-ENaC with either 1) the alpha-subunit first membrane-spanning domain and short downstream hydrophobic domain (alpha-M1H1); 2) alpha-M1H1 and its downstream hydrophilic extracellular loop (alpha-M1H1-ECL); 3) the membrane-spanning domain of a control type 2 transmembrane protein (glutamyl transpeptidase; gamma-GT) fused to the alpha-ECL (gamma-GT-alpha-ECL); 4) the extracellular domain of a control type 1 transmembrane protein (Tac) fused to the alpha-subunit second membrane-spanning domain and short upstream hydrophobic domain (Tac-alpha-H2M2); or 5) the alpha-subunit cytoplasmic COOH terminus (alpha-Ct) significantly reduced amiloride-sensitive Na+ currents in X. laevis oocytes. Functional expression of Na+ channels was not inhibited when full-length alphabetagamma-ENaC was coexpressed with either 1) the a...Continue Reading

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Citations

Sep 1, 2005·Proceedings of the National Academy of Sciences of the United States of America·Heping LinClaudio W Pikielny
Aug 1, 2007·The Journal of Biological Chemistry·Ossama B KashlanThomas R Kleyman
Jul 29, 2010·The Journal of Biological Chemistry·Gunhild M MuellerRebecca P Hughey
Jan 1, 2004·The Journal of Biological Chemistry·Shaohu ShengThomas R Kleyman
Jun 20, 2018·Current Opinion in Nephrology and Hypertension·Teresa M Buck, Jeffrey L Brodsky
Oct 26, 2010·Pflügers Archiv : European journal of physiology·Daniela Rotin, Olivier Staub
Aug 30, 2008·Journal of the American Society of Nephrology : JASN·Vivek Bhalla, Kenneth R Hallows
Apr 3, 2014·The Journal of Biological Chemistry·Anindit MukherjeeRebecca P Hughey
Aug 5, 2004·The Journal of Biological Chemistry·Jonathan LebowitzJohn P Johnson

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