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|Title:||Regulation of the epithelial sodium channel by N4WBP5A, a novel Nedd4/Nedd4-2-interacting protein|
|Citation:||Journal of Biological Chemistry, 2002; 277(33):29406-29416|
|Publisher:||Amer Soc Biochemistry Molecular Biology Inc|
|Angelos-Aristeidis Konstas, Linda M. Shearwin-Whyatt, Andrew B. Fotia, Brian Degger, Daniela Riccardi, David I. Cook, Christoph Korbmacher and Sharad Kumar|
|Abstract:||The amiloride-sensitive epithelial sodium channel (ENaC) plays a critical role in fluid and electrolyte homeostasis and consists of α, β, and γ subunits. The carboxyl terminus of each ENaC subunit contains a PPXY motif that is believed to be important for interaction with the WW domains of the ubiquitin-protein ligases, Nedd4 and Nedd4-2. Disruption of this interaction, as in Liddle’s syndrome where mutations delete or alter the PPXY motif of either the β or γ subunits, has been shown to result in increased ENaC activity and arterial hypertension. Here we present evidence that N4WBP5A, a novel Nedd4/Nedd4-2-binding protein, is a potential regulator of ENaC. In Xenopus laevis oocytes N4WBP5A increases surface expression of ENaC by reducing the rate of ENaC retrieval. We further demonstrate that N4WBP5A prevents sodium feedback inhibition of ENaC possibly by interfering with the xNedd4-2-mediated regulation of ENaC. As N4WBP5A binds Nedd4/Nedd4-2 via PPXY motif/WW domain interactions and appears to be associated with specific intracellular vesicles, we propose that N4WBP5A functions by regulating Nedd4/ Nedd4-2 availability and trafficking. Because N4WBP5A is highly expressed in native renal collecting duct and other tissues that express ENaC, it is a likely candidate to modulate ENaC function in vivo.|
|Keywords:||Oocytes; Cell Line; Animals; Xenopus laevis; Humans; Rats; Rats, Wistar; Sodium; Cysteine Endopeptidases; Ligases; Ubiquitin-Protein Ligases; Carrier Proteins; Calcium-Binding Proteins; Sodium Channels; Membrane Proteins; Male; Caspase 2; Endosomal Sorting Complexes Required for Transport; Epithelial Sodium Channels|
|Rights:||Copyright © 2012 by American Society for Biochemistry and Molecular Biology|
|Appears in Collections:||Medicine publications|
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