| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Howard Hughes Medical Institute, Departments of Pediatrics, Internal Medicine, and Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242
The epithelial
Na+ channel (ENaC) is comprised of
three homologous subunits: 
, 
, and 
, all of which are required
for formation of the fully functional channel. This channel is
responsible for salt reabsorption in the kidney, the airway, and the
large bowel. Mutations in ENaC can cause human disease by increasing
channel function in Liddle's syndrome, a form of hereditary
hypertension, or by decreasing channel function in
pseudohypoaldosteronism type I, a salt-wasting disease of infancy. We
previously showed that ENaC is expressed on the cell surface as a
minimally glycosylated, Triton-insoluble protein. In the present
study we found that ENaC existed initially as a Triton-soluble protein
that contained high-mannose glycosylation, presumably in the
endoplasmic reticulum. This form of the protein disappeared as the
Triton-insoluble, minimally glycosylated form became the more prevalent
species. In pulse-chase studies of individually expressed subunits, we
found that the Triton-soluble form of -ENaC accumulated initially,
whereas the Triton-soluble form of -ENaC decreased throughout the
time course. However, when all three subunits were coexpressed, the
- and -subunits showed a similar pattern. The complex became
Triton insoluble at some point after the endoplasmic reticulum, as
incubation at 15°C blocked the conversion to the insoluble form.
Deletion of the carboxy-terminal tail of -ENaC causes Liddle's
syndrome. This mutation increased the amount of newly synthesized
Triton-insoluble ENaC heteromultimers but did not affect the half-life
of insoluble protein. Therefore, subunit composition and mutations in
individual subunits can influence biosynthesis of the ENaC complex.
degenerin/epithelial sodium channel; sodium channel; subunit assembly; Triton solubility
This article has been cited by other articles:
|
|
 |
|
  C. Balut, P. Steels, M. Radu, M. Ameloot, W. V. Driessche, and D. Jans Membrane cholesterol extraction decreases Na+ transport in A6 renal epithelia Am J Physiol Cell Physiol, January 1, 2006; 290(1): C87 - C94. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. G. Shlyonsky, F. Mies, and S. Sariban-Sohraby Epithelial sodium channel activity in detergent-resistant membrane microdomains Am J Physiol Renal Physiol, January 1, 2003; 284(1): F182 - F188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. G. Hill, B. An, and J. P. Johnson Endogenously Expressed Epithelial Sodium Channel Is Present in Lipid Rafts in A6 Cells J. Biol. Chem., September 6, 2002; 277(37): 33541 - 33544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Rotin, V. Kanelis, and L. Schild Trafficking and cell surface stability of ENaC Am J Physiol Renal Physiol, September 1, 2001; 281(3): F391 - F399. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Hanwell, T. Ishikawa, R. Saleki, and D. Rotin Trafficking and Cell Surface Stability of the Epithelial Na+ Channel Expressed in Epithelial Madin-Darby Canine Kidney Cells J. Biol. Chem., March 15, 2002; 277(12): 9772 - 9779. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
