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

Aldosterone regulates Na super(+) transport in the distal nephron through multiple mechanisms that include the transcriptional control of epithelial sodium channel (ENaC) and Na super(+)/K super(+)-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-kinaseIII beta (PI4KIII beta ). We report rapid ENaC gamma 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 super(+)/K super(+)-ATPase alpha and beta subunits showed aberrant localization. PKD1 and PI4KIII beta localize to the TGN, and aldosterone induced an interaction between PKD1 and PI4KIII beta following aldosterone treatment. This study reveals a novel mechanism for rapid regulation of ENaC and the Na super(+)/K super(+)-ATPase, via directed trafficking through PKD1-PI4KIII beta signalling at the level of the TGN.