AJP - Renal Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Renal Physiol (March 15, 2005). doi:10.1152/ajprenal.00179.2002
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
289/1/F107    most recent
00179.2002v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Malik, B.
Right arrow Articles by Eaton, D. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Malik, B.
Right arrow Articles by Eaton, D. C.
Submitted on May 9, 2002
Accepted on March 1, 2005

Role of Nedd4-2 and Polyubiquitination in Epithelial Sodium Channel Degradation in Untransfected Renal A6 Cells Expressing Endogenous ENaC Subunits

B. Malik1*, Q. Yue1, G. Yue1, XJ Chen1, S. R. Price2, W. E. Mitch2, and D. C. Eaton1

1 Department of Physiology, Emory University, Atlanta, GA, none
2 Renal Division, Emory University, Atlanta, GA, none

* To whom correspondence should be addressed. E-mail: bmalik{at}physio.emory.edu.

Amiloride-sensitive epithelial sodium channels (ENaC) are responsible for trans-epithelial Na+ transport in the kidney, lung and colon. The channel consists of three subunits ({alpha}, {beta} and {gamma}). In MDCK cells and Xenopus oocytes transfected with all three ENaC subunits, Neural-precursor-cell- expressed-developmentally-down-regulated-protein (Nedd4-2) promotes ubiquitin conjugation of ENaC. For native proteins in some cells, ubiquitin conjugation is a signal for their degradation by the ubiquitin-proteasome pathway while in other cell types, ubiquitin conjugation is a signal for endocytosis and lysosomal protein degradation. When ENaC is transfected into MDCK cells, ubiquitin conjugation leads to lysosomal degradation. In this paper we characterize the involvement of the ubiquitin-proteasome proteolytic pathway in the regulation of functional ENaC in untransfected renal A6 cells expressing native ENaC subunits. In contrast to transfected cells, we show that total cellular {alpha}, {beta} and {gamma} ENaC subunits are polyubiquitinated and that ubiquitin conjugation of subunits increases when the cells are treated with a proteasome inhibitor. We show that Nedd4-2 is associated with {alpha} and {beta} subunits and is associated with apical membrane. We also show the Nedd4-2 can regulate the number of functional ENaC subunits in the apical membrane. The results reported here suggest that the ubiquitin-proteasome proteolytic pathway is an important determinant of ENaC function in untransfected renal cells expressing endogenous ENaC.




This article has been cited by other articles:


Home page
 J EndocrinolHome page
C. E Hills, P. E Squires, and R. Bland
Serum and glucocorticoid regulated kinase and disturbed renal sodium transport in diabetes
J. Endocrinol., December 1, 2008; 199(3): 343 - 349.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. P. Albert, A. M. Woollhead, O. J. Mace, and D. L. Baines
AICAR decreases the activity of two distinct amiloride-sensitive Na+-permeable channels in H441 human lung epithelial cell monolayers
Am J Physiol Lung Cell Mol Physiol, November 1, 2008; 295(5): L837 - L848.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
V. Bhalla and K. R. Hallows
Mechanisms of ENaC Regulation and Clinical Implications
J. Am. Soc. Nephrol., October 1, 2008; 19(10): 1845 - 1854.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
O. J. Mace, A. M. Woollhead, and D. L. Baines
AICAR activates AMPK and alters PIP2 association with the epithelial sodium channel ENaC to inhibit Na+ transport in H441 lung epithelial cells
J. Physiol., September 15, 2008; 586(18): 4541 - 4557.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
V. Bhalla, R. Soundararajan, A. C. Pao, H. Li, and D. Pearce
Disinhibitory pathways for control of sodium transport: regulation of ENaC by SGK1 and GILZ
Am J Physiol Renal Physiol, October 1, 2006; 291(4): F714 - F721.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
V. Bhalla, N. M. Oyster, A. C. Fitch, M. A. Wijngaarden, D. Neumann, U. Schlattner, D. Pearce, and K. R. Hallows
AMP-activated Kinase Inhibits the Epithelial Na+ Channel through Functional Regulation of the Ubiquitin Ligase Nedd4-2
J. Biol. Chem., September 8, 2006; 281(36): 26159 - 26169.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
S. Faroqui, S. Sheriff, and H. Amlal
Metabolic acidosis has dual effects on sodium handling by rat kidney
Am J Physiol Renal Physiol, August 1, 2006; 291(2): F322 - F331.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
B. Malik, S. R. Price, W. E. Mitch, Q. Yue, and D. C. Eaton
Regulation of epithelial sodium channels by the ubiquitin-proteasome proteolytic pathway
Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1285 - F1294.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
O. Staub and F. Verrey
Impact of Nedd4 Proteins and Serum and Glucocorticoid-Induced Kinases on Epithelial Na+ Transport in the Distal Nephron
J. Am. Soc. Nephrol., November 1, 2005; 16(11): 3167 - 3174.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.