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Protein kinase D1 modulates aldosterone‐induced ENaC trafficking and regulation in M1 renal cortical collecting duct cells
Author(s) -
Dooley Ruth,
Harvey Brian J,
Thomas Warren
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.606.28
Subject(s) - epithelial sodium channel , aldosterone , medicine , gene knockdown , endocrinology , microbiology and biotechnology , chemistry , biology , sodium , biochemistry , apoptosis , organic chemistry
Aldosterone stimulates the phosphorylation and activation of Protein Kinase D1 in M1 cells through the transactivation of EGFR (1). PKD1 mediates rapid aldosterone‐induced subcellular trafficking of ENaC (2). ENaCα is under transcriptional control of the mineralocorticoid receptor while ENaCβ and ENaCγ are constitutively expressed in the distal nephron. Using siRNA‐mediated stable knockdown of PKD1, transepithelial current measurements (I TE ) and confocal microscopy, we examined the role of PKD1 in the regulation of ENaC trafficking and activity in M1 cells. Aldosterone (10nM) increased amiloride‐sensitive I TE from 1 ± 0.21 μA/cm 2 to 7 ± 0.86 μA/cm 2 (n= 8, p < 0.005) in wild type M1 cells within 24h. This effect was reduced by 71.5% in the PKD1 suppressed cells. ENaCα expression was increased in wild type cells treated with aldosterone for 24h and this response was absent in PKD1 knockdown cells. Aldosterone stimulated the apical membrane insertion of ENaCβ in wild type cells, whereas no trafficking effect was observed in the PKD1 suppressed cells. PKD1 plays a central role in the aldosterone‐mediated regulation of ENaC through both transcriptional control and subcellular trafficking. Funded by Wellcome Trust, Higher Education Authority of Ireland and Science Foundation Ireland.