Document Detail


Nedd4-2 does not regulate wt-CFTR in human airway epithelial cells.
MedLine Citation:
PMID:  22904170     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Katja Koeppen; Chris Chapline; J Denry Sato; Bruce A Stanton
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-08-17
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  303     ISSN:  1522-1504     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-16     Completed Date:  2012-12-26     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L720-7     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, 604 Remsen, Hanover, NH 03755, USA. Katja.Koeppen@Dartmouth.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Antiporters / metabolism
Bronchi / cytology
Cell Membrane / metabolism
Cells, Cultured
Chlorides / metabolism
Cystic Fibrosis / metabolism
Cystic Fibrosis Transmembrane Conductance Regulator / genetics,  metabolism*
Endosomal Sorting Complexes Required for Transport / genetics,  metabolism*
Humans
Membrane Potentials / physiology
Oocytes / physiology
Phosphoproteins / metabolism
RNA, Small Interfering / genetics
Respiratory Mucosa / cytology*,  metabolism*
Sodium-Hydrogen Antiporter / metabolism
Ubiquitin-Protein Ligases / genetics,  metabolism*
Ubiquitination / physiology
Xenopus
Grant Support
ID/Acronym/Agency:
P20 RR016463/RR/NCRR NIH HHS; R01 HL074175/HL/NHLBI NIH HHS; R01 HL074175/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antiporters; 0/CFTR protein, human; 0/Chlorides; 0/Endosomal Sorting Complexes Required for Transport; 0/Phosphoproteins; 0/RNA, Small Interfering; 0/SLC26A9 protein, human; 0/Sodium-Hydrogen Antiporter; 0/sodium-hydrogen exchanger regulatory factor; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator; EC 6.3.2.19/Nedd4 ubiquitin protein ligases; EC 6.3.2.19/Ubiquitin-Protein Ligases
Comments/Corrections

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