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.
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 30min 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.
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CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-N GENE-Y GENE-Y GENE-N GENE-N GENE-N GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y GENE-N GENE-Y GENE-Y GENE-Y GENE-Y GENE-N GENE-N GENE-Y GENE-Y
Aldosterone Na(+) K(+) Na(+) K(+) Aldosterone Na(+) phosphatidylinositol ouabain Na(+) K(+) aldosterone aldosterone Aldosterone Na(+) K(+) phosphatidylinositol ENaC Na(+)/K(+)-ATPase PKD1 PI4KIIIβ sodium channel ENaC Na(+)/K(+)-ATPase Protein Kinase D1 PKD1 PKD phosphatidylinositol 4-kinaseIIIβ PI4KIIIβ ENaCγ PKD1 PKD1 Na(+)/K(+)-ATPase α and β PKD1 PI4KIIIβ PKD1 PI4KIIIβ ENaC Na(+)/K(+)-ATPase protein kinase D1 phosphatidylinositol 4-kinaseIIIβ