Protein Kinase D1 Modulates Aldosterone-Induced ENaC Activity in a Renal Cortical Collecting Duct Cell Line Victoria McEneaney Ruth Dooley Yamil R. Yusef Niamh Keating Ursula Quinn Brian J. Harvey Warren Thomas 10779/rcsi.10786295.v1 https://repository.rcsi.com/articles/journal_contribution/Protein_Kinase_D1_Modulates_Aldosterone-Induced_ENaC_Activity_in_a_Renal_Cortical_Collecting_Duct_Cell_Line/10786295 <p>Aldosterone treatment of M1-CCD cells stimulated an increase in epithelial Na+ channel (ENaC) alpha-subunit expression that was mainly localized to the apical membrane. PKD1 suppressed cells constitutively expressed ENaC alpha at low abundance, with no increase after aldosterone treatment. Here ENaC alpha was mainly localized proximal to the basolateral surface of the epithelium both before and after aldosterone treatment. Apical membrane insertion of ENaC beta in response to aldosterone treatment was also sensitive to PKD1 suppression as was the aldosterone-induced rise in the amiloride-sensitive, trans-epithelial current (ITE). The interaction of the mineralocorticoid receptor (MR) with specific elements in the promoters of aldosterone responsive genes is stabilized by ligand interaction and phosphorylation. PKD1 suppression inhibited aldosterone-induced SGK-1 expression. The nuclear localization of MR was also blocked by PKD1 suppression and MEK antagonism implicating both these kinases in MR nuclear stabilization. PKD1 thus modulates aldosterone-induced ENaC activity through the modulation of sub-cellular trafficking and the stabilization of MR nuclear localization.</p> 2019-11-22 16:38:25 Aldosterone ENaC Protein Kinase D Renal Cortical collecting duct cell line Hypertension Molecular Medicine