Aldosterone-induced ENaC and basal Na+/K+-ATPase trafficking via protein kinase D1-phosphatidylinositol 4-kinaseIIIβ trans Golgi signalling in M1 cortical collecting duct cells

Mol Cell Endocrinol. 2013 Jun 15;372(1-2):86-95. doi: 10.1016/j.mce.2013.03.011. Epub 2013 Mar 26.

Abstract

Aldosterone regulates Na(+) transport in the distal nephron through multiple mechanisms that include the transcriptional control of epithelial sodium channel (ENaC) and Na(+)/K(+)-ATPase subunits. Aldosterone also induces the rapid phosphorylation of Protein Kinase D1 (PKD1). PKD isoforms regulate protein trafficking, by the control of vesicle fission from the trans Golgi network (TGN) through activation of phosphatidylinositol 4-kinaseIIIβ (PI4KIIIβ). We report rapid ENaCγ translocation to the plasma membrane after 30 min aldosterone treatment in polarized M1 cortical collecting duct cells, which was significantly impaired in PKD1 shRNA-mediated knockdown cells. In PKD1-deficient cells, the ouabain-sensitive current was significantly reduced and Na(+)/K(+)-ATPase α and β subunits showed aberrant localization. PKD1 and PI4KIIIβ localize to the TGN, and aldosterone induced an interaction between PKD1 and PI4KIIIβ following aldosterone treatment. This study reveals a novel mechanism for rapid regulation of ENaC and the Na(+)/K(+)-ATPase, via directed trafficking through PKD1-PI4KIIIβ signalling at the level of the TGN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone / physiology*
  • Animals
  • Cell Line
  • Cell Membrane / metabolism
  • Cell Polarity
  • Epithelial Sodium Channels / metabolism*
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Kidney Tubules, Collecting / cytology*
  • Mice
  • Mice, Transgenic
  • Minor Histocompatibility Antigens
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Protein Interaction Maps
  • Protein Kinase C / metabolism*
  • Protein Transport
  • Signal Transduction
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Transport Vesicles / metabolism
  • trans-Golgi Network / enzymology*
  • trans-Golgi Network / metabolism

Substances

  • Epithelial Sodium Channels
  • Minor Histocompatibility Antigens
  • Aldosterone
  • Phosphotransferases (Alcohol Group Acceptor)
  • phosphatidylinositol phosphate 4-kinase
  • protein kinase D
  • Protein Kinase C
  • Sodium-Potassium-Exchanging ATPase