SGK1 increases Na,K-ATP cell-surface expression and function in Xenopus laevis oocytes

Pflugers Arch. 2004 Apr;448(1):29-35. doi: 10.1007/s00424-003-1222-9. Epub 2004 Jan 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone / pharmacology
  • Animals
  • Blotting, Western
  • Electrophoresis, Polyacrylamide Gel
  • Epithelial Sodium Channels
  • Female
  • Gene Expression
  • Immediate-Early Proteins
  • Kidney Tubules, Collecting / metabolism
  • Large Neutral Amino Acid-Transporter 1 / metabolism
  • Membrane Proteins / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Oocytes / metabolism*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / physiology*
  • Protein Transport
  • Sodium Channels / metabolism
  • Sodium-Phosphate Cotransporter Proteins
  • Sodium-Potassium-Exchanging ATPase / genetics
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Symporters / metabolism
  • Xenopus laevis

Substances

  • Epithelial Sodium Channels
  • Immediate-Early Proteins
  • Large Neutral Amino Acid-Transporter 1
  • Membrane Proteins
  • Nuclear Proteins
  • Sodium Channels
  • Sodium-Phosphate Cotransporter Proteins
  • Symporters
  • Aldosterone
  • Protein Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase
  • Sodium-Potassium-Exchanging ATPase