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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-14475

Fakitsas, P; Adam, G; Daidié, D; van Bemmelen, M X; Fouladkou, F; Patrignani, A; Wagner, U; Warth, R; Camargo, S M R; Staub, O; Verrey, F (2007). Early aldosterone-induced gene product regulates the epithelial sodium channel by deubiquitylation. Journal of the American Society of Nephrology (JASN), 18(4):1084-1092.

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Abstract

The mineralocorticoid hormone aldosterone controls sodium reabsorption and BP largely by regulating the cell-surface expression and function of the epithelial sodium channel (ENaC) in target kidney tubules. Part of the stimulatory effect of aldosterone on ENaC is mediated by the induction of serum- and glucocorticoid-regulated kinase 1 (Sgk1), a kinase that interferes with the ubiquitylation of ENaC by ubiquitin-protein ligase Nedd4-2. In vivo early aldosterone-regulated mRNA now has been identified in microselected mouse distal nephron by microarray. From 22 mRNA that displayed a two-fold or more change, 13 were downregulated and nine were upregulated. Besides Sgk1, the induced mRNA include Grem2 (protein related to DAN and cerebrus [PRDC]), activating transcription factor 3, cAMP responsive element modulator, and the ubiquitin-specific protease Usp2-45. The induction of this last enzyme isoform was verified in mouse distal nephron tubule at the protein level. With the use of Hek293 cells, Xenopus oocytes, and mpkCCD(c14) cells as expression systems, it was shown that Usp2-45 deubiquitylates ENaC and stimulates ENaC-mediated sodium transport, an effect that is not additive to that of Sgk1. A deubiquitylating enzyme that targets ENaC in vitro and thus may play a role in sodium transport regulation was identified within a series of new in vivo early aldosterone-regulated gene products.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Functional Genomics Center Zurich
04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

08 University Research Priority Programs > Systems Biology / Functional Genomics
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:April 2007
Deposited On:22 Mar 2009 09:43
Last Modified:28 Nov 2013 00:56
Publisher:American Society of Nephrology
ISSN:1046-6673
Publisher DOI:10.1681/ASN.2006080902
PubMed ID:17344426

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