Trafficking and cell surface stability of ENaC.
The epithelial Na(+) channel (ENaC) plays a key role in the regulation of Na(+) and water absorption in several epithelia, including those of the distal nephron, distal colon, and lung. Accordingly, mutations in ENaC leading to reduced or increased channel activity cause human diseases such as pseudohypoaldosteronism type I or Liddle's syndrome, respectively. The gain of ENaC function in Liddle's syndrome is associated with increased activity and stability of the channel at the plasma membrane. Thus understanding the regulation of channel processing and trafficking to and stability at the cell surface is of fundamental importance. This review describes some of the recent advances in our understanding of ENaC trafficking, including the role of glycosylation, ENaC solubility in nonionic detergent, targeting signal(s) and hormones. It also describes the regulation of ENaC stability at the cell surface and the roles of the ubiquitin ligase Nedd4 (and ubiquitination) and clathrin-mediated endocytosis in that regulation.
Rotin
D
D
Program in Cell Biology and Biochemistry, The Hospital for Sick Children, University of Toronto, 555 University Ave., Toronto, Ontario, Canada, M5G 1X8. drotin@sickkids.on.ca
Kanelis
V
V
Schild
L
L
D000818:Animals; D002462:Cell Membrane / Q000502:physiology*; D004705:Endocytosis; D004847:Epithelial Cells / Q000502:physiology*; D053503:Epithelial Sodium Channels; D006801:Humans; D006929:Hyperaldosteronism / Q000503:physiopathology; D007668:Kidney / Q000502:physiology* / Q000503:physiopathology; D011487:Protein Conformation; D015222:Sodium Channels / Q000737:chemistry / Q000502:physiology*; D013577:Syndrome
D053503:Epithelial Sodium Channels; D015222:Sodium Channels