Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR), a Cl(-) channel in airway epithelial cells, plays an important role in maintaining the volume of the airway surface liquid and therefore mucociliary clearance of respiratory pathogens. A recent study has shown that the E3 ubiquitin ligase Neural precursor cells expressed developmentally downregulated (Nedd4-2) ubiquitinates ΔF508-CFTR in pancreatic epithelial cells and that siRNA-mediated silencing of Nedd4-2 increases plasma membrane ΔF508-CFTR. Because the role of Nedd4-2 in regulating wild-type (wt)-CFTR in airway epithelial cells is unknown, studies were conducted to test the hypothesis that Nedd4-2 also ubiquitinates wt-CFTR and regulates its plasma membrane abundance. We found that Nedd4-2 did not affect wt-CFTR Cl(-) currents in Xenopus oocytes. Likewise, overexpression of Nedd4-2 in human airway epithelial cells did not alter the amount of ubiquitinated wt-CFTR. siRNA knockdown of Nedd4-2 in human airway epithelial cells had no effect on ubiquitination or apical plasma membrane abundance of wt-CFTR. Thus Nedd4-2 does not ubiquitinate and thereby regulate wt-CFTR in human airway epithelial cells.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antiporters / metabolism
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Bronchi / cytology
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Cell Membrane / metabolism
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Cells, Cultured
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Chlorides / metabolism
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Cystic Fibrosis / metabolism
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Cystic Fibrosis Transmembrane Conductance Regulator / genetics
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Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
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Endosomal Sorting Complexes Required for Transport / genetics
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Endosomal Sorting Complexes Required for Transport / metabolism*
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Humans
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Membrane Potentials / physiology
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Nedd4 Ubiquitin Protein Ligases
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Oocytes / physiology
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Phosphoproteins / metabolism
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RNA, Small Interfering / genetics
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Respiratory Mucosa / cytology*
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Respiratory Mucosa / metabolism*
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Sodium-Hydrogen Exchangers / metabolism
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Sulfate Transporters
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Ubiquitin-Protein Ligases / genetics
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Ubiquitin-Protein Ligases / metabolism*
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Ubiquitination / physiology
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Xenopus
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Xenopus Proteins
Substances
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Antiporters
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CFTR protein, human
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Chlorides
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Endosomal Sorting Complexes Required for Transport
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Phosphoproteins
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RNA, Small Interfering
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SLC26A9 protein, human
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Sodium-Hydrogen Exchangers
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Sulfate Transporters
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Xenopus Proteins
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sodium-hydrogen exchanger regulatory factor
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Cystic Fibrosis Transmembrane Conductance Regulator
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Nedd4 Ubiquitin Protein Ligases
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Nedd4 protein, Xenopus
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Nedd4 protein, human
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Nedd4L protein, human
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nedd4l protein, Xenopus
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Ubiquitin-Protein Ligases