title: SGK1 increases Na,K-ATP cell-surface expression and function in Xenopus laevis oocytes.
abstract: The Na(+)-retaining hormone aldosterone increases the cell-surface expression of the luminal epithelial sodium channel (ENaC) and the basolateral Na(+) pump (Na,K-ATPase) in aldosterone-sensitive distal nephron cells in a coordinated fashion. To address the question of whether aldosterone-induced serum and glucocorticoid-regulated kinase-1 (SGK1) might be involved in mediating this regulation of Na,K-ATPase subcellular localization, similar to that of the epithelial Na(+) channel (ENaC), we co-expressed the Na,K-ATPase (rat alpha 1- and Xenopus laevis beta 1-subunits) and Xenopus SGK1 in Xenopus oocytes. Measurements of the Na(+) pump current showed that wild-type SGK1 increases the function of exogenous Na,K-ATPase at the surface of Xenopus oocytes. This appeared to be secondary to an increase in Na,K-ATPase cell-surface expression as visualized by Western blotting of surface-biotinylated proteins. In contrast, the functional surface expression of two other exogenous transporters, the heterodimeric amino acid transporter LAT1-4F2hc and the Na(+)/phosphate cotransporter NaPi-IIa, was not increased by SGK1 co-expression. The total pool of exogenous Na,K-ATPase was increased by the co-expression of SGK1, and similarly also by ENaC co-expression. This latter effect depended on the [Na(+)] of the buffer and was not additive to that of SGK1. When the total Na,K-ATPase was increased by ENaC co-expression, SGK1 still increased Na,K-ATPase cell-surface expression. These observations in Xenopus oocytes suggest the possibility that SGK1 induction and/or activation could participate in the coordinated regulation of Na,K-ATPase and ENaC cell-surface expression in the aldosterone-sensitive distal nephron.
authors.affiliation: Institute of Physiology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Marija
authors.initials: M
authors.lastname: Zecevic
authors.forename: Dirk
authors.initials: D
authors.lastname: Heitzmann
authors.forename: Simone M R
authors.initials: SM
authors.lastname: Camargo
authors.forename: Francois
authors.initials: F
authors.lastname: Verrey
mesh_terms: D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D053503:Epithelial Sodium Channels; D005260:Female; D015870:Gene Expression; D017874:Immediate-Early Proteins; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D027283:Large Neutral Amino Acid-Transporter 1 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D009865:Oocytes / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D021381:Protein Transport; D015222:Sodium Channels / Q000378:metabolism; D050608:Sodium-Phosphate Cotransporter Proteins; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D027981:Symporters / Q000378:metabolism; D014982:Xenopus laevis; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D000450:Aldosterone; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D027283:Large Neutral Amino Acid-Transporter 1; D008565:Membrane Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D015222:Sodium Channels; D050608:Sodium-Phosphate Cotransporter Proteins; D000254:Sodium-Potassium-Exchanging ATPase; D027981:Symporters; D000099184:Serum-Glucocorticoid Regulated Kinases