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Type: Journal article
Title: The Nedd4-like protein KIAA0439 is a potential regulator of the epithelial sodium channel
Author: Harvey, K.
Dinudom, A.
Cook, D.
Kumar, S.
Citation: Journal of Biological Chemistry, 2001; 276(11):8597-8601
Publisher: Amer Soc Biochemistry Molecular Biology Inc
Issue Date: 2001
ISSN: 0021-9258
Statement of
Kieran F. Harvey, Anuwat Dinudom, David I. Cook and Sharad Kumar
Abstract: The amiloride-sensitive epithelial sodium channel (ENaC) plays a critical role in fluid and electrolyte homeostasis and consists of alpha, beta, and gamma subunits. The carboxyl terminus of each ENaC subunit contains a PPxY, motif which is believed to be important for interaction with the WW domains of the ubiquitin-protein ligase, Nedd4. Disruption of this interaction, as in Liddle's syndrome, where mutations delete or alter the PPxY motif of either the beta or gamma subunits, has been proposed to result in increased ENaC activity. Here we present evidence that KIAA0439 protein, a close relative of Nedd4, is also a potential regulator of ENaC. We demonstrate that KIAA0439 WW domains bind all three ENaC subunits. We show that a recombinant KIAA0439 WW domain protein acts as a dominant negative mutant that can interfere with the Na(+)-dependent feedback inhibition of ENaC in whole-cell patch clamp experiments. We propose that KIAA0439 and Nedd4 proteins either play a redundant role in ENaC regulation or function in a tissue- and/or signal-specific manner to down-regulate ENaC.
Keywords: Animals
Ubiquitin-Protein Ligases
Calcium-Binding Proteins
Sodium Channels
Protein Subunits
RNA, Messenger
Endosomal Sorting Complexes Required for Transport
Epithelial Sodium Channels
Nedd4 Ubiquitin Protein Ligases
DOI: 10.1074/jbc.C000906200
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Medicine publications

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