Peer Reviewed

1

Document Type

Article

Publication Date

2010

Keywords

Aldosterone, ENaC, Protein Kinase D, Renal Cortical collecting duct cell line, Hypertension

Comments

The original article is available at www.sciencedirect.com

Abstract

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.

Disciplines

Medical Molecular Biology | Medical Sciences

Citation

McEneaney V, Dooley R, Yusef YR, Keating N, Quinn U, Harvey BJ, Thomas W. Protein Kinase D1 Modulates Aldosterone-Induced ENaC Activity in a Renal Cortical Collecting Duct Cell Line. Molecular and Cellular Endocrinology. 2010;325(1-2):8-17.

PubMed ID

20434520

DOI Link

10.1016/j.mce.2010.04.019

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

Share

COinS