| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
INVITED REVIEW
1Department of Physiology and 2Renal Division, Emory University, Atlanta, Georgia; and 3Department of Nephrology, Baylor College of Medicine, Houston, Texas
Amiloride-sensitive epithelial Na+ channels (ENaC) play a crucial role in Na+ transport and fluid reabsorption in the kidney, lung, and colon. The magnitude of ENaC-mediated Na+ transport in epithelial cells depends on the average open probability of the channels and the number of channels on the apical surface of epithelial cells. The number of channels in the apical membrane, in turn, depends on a balance between the rate of ENaC insertion and the rate of removal from the apical membrane. ENaC is made up of three homologous subunits: 
, 
, and 
. The COOH-terminal domain of all three subunits is intracellular and contains a proline-rich motif (PPxY). Mutations or deletion of this PPxY motif in the - and -subunits prevent the binding of one isoform of a specific ubiquitin ligase, neural precursor cell-expressed, developmentally downregulated protein (Nedd4–2), to the channel in vitro and in transfected cell systems, thereby impeding ubiquitin conjugation of the channel subunits. Ubiquitin conjugation would seem to imply that ENaC turnover is determined by the ubiquitin-proteasome system, but when Madin-Darby canine kidney cells are transfected with ENaC, ubiquitin conjugation apparently leads to lysosomal degradation. However, in untransfected renal cells (A6) expressing endogenous ENaC, ENaC is indeed degraded by the ubiquitin-proteasome system. Nonetheless, in both transfected and untransfected cells, the rate of ENaC degradation is apparently controlled by Nedd4–2 activity. In this review, we discuss the role of the ubiquitin conjugation and the alternative degradative pathways (lysosomal or proteasomal) in regulating the rate of ENaC turnover in untransfected renal cells and compare this regulation to that of transfected cell systems.
Nedd4; Sgk; A6 cells; amiloride sensitive; membrane-spanning protein
This article has been cited by other articles:
|
|
 |
|
  D. Ruffieux-Daidie, O. Poirot, S. Boulkroun, F. Verrey, S. Kellenberger, and O. Staub Deubiquitylation Regulates Activation and Proteolytic Cleavage of ENaC J. Am. Soc. Nephrol., November 1, 2008; 19(11): 2170 - 2180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Chen, H. Huang, O. Frohlich, Y. Yang, J. D. Klein, S. R. Price, and J. M. Sands MDM2 E3 ubiquitin ligase mediates UT-A1 urea transporter ubiquitination and degradation Am J Physiol Renal Physiol, November 1, 2008; 295(5): F1528 - F1534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Boulkroun, D. Ruffieux-Daidie, J.-J. Vitagliano, O. Poirot, R.-P. Charles, D. Lagnaz, D. Firsov, S. Kellenberger, and O. Staub Vasopressin-inducible ubiquitin-specific protease 10 increases ENaC cell surface expression by deubiquitylating and stabilizing sorting nexin 3 Am J Physiol Renal Physiol, October 1, 2008; 295(4): F889 - F900. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Heitzmann and R. Warth Physiology and Pathophysiology of Potassium Channels in Gastrointestinal Epithelia Physiol Rev, July 1, 2008; 88(3): 1119 - 1182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. S. Raikwar and C. P. Thomas Nedd4-2 isoforms ubiquitinate individual epithelial sodium channel subunits and reduce surface expression and function of the epithelial sodium channel Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1157 - F1165. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
