![]()
|
|
||||||||
(Received for publication, July 2, 1997)
From the Howard Hughes Medical Institute and Departments of
Internal Medicine and Physiology and Biophysics, University of Iowa
College of Medicine, Iowa City, Iowa 52242
The human epithelial sodium channel (hENaC)
mediates Na+ transport across the apical membrane of
epithelia, and mutations in hENaC result in hypertensive and
salt-wasting diseases. In heterologous expression systems, maximal
hENaC function requires co-expression of three homologous proteins, the
Volume 272, Number 43,
Issue of October 24, 1997
pp. 27295-27300
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
Interactions between Subunits of the Human Epithelial Sodium
Channel
,
, and
hENaC subunits, suggesting that hENaC subunits
interact to form a multimeric channel complex. Using a
co-immunoprecipitation assay, we found that hENaC subunits associated
tightly to form homo- and heteromeric complexes and that the
association between subunits occurred early in channel biosynthesis.
Deletion analysis of
hENaC revealed that the N terminus was
sufficient but not necessary for co-precipitation of
hENaC, and that
both the N terminus and the second transmembrane segment (M2) were
required for
subunit function. The biochemical studies were
supported by functional studies. Co-expression of
subunits lacking
M2 with full-length hENaC subunits revealed an inhibitory effect on
hENaC channel function that appeared to be mediated by the cytoplasmic
N terminus of
, and was consistent with the assembly of
nonfunctional subunits into the channel complex. We conclude that the N
terminus of
hENaC is involved in channel assembly.
![]()
CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
This article has been cited by other articles:
![]() |
M. D. Carattino, R. P. Hughey, and T. R. Kleyman Proteolytic Processing of the Epithelial Sodium Channel {gamma} Subunit Has a Dominant Role in Channel Activation J. Biol. Chem., September 12, 2008; 283(37): 25290 - 25295. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. P. Gannon, L. G. VanLandingham, N. L. Jernigan, S. C. Grifoni, G. Hamilton, and H. A. Drummond Impaired pressure-induced constriction in mouse middle cerebral arteries of ASIC2 knockout mice Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1793 - H1803. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. M. Mueller, O. B. Kashlan, J. B. Bruns, A. B. Maarouf, M. Aridor, T. R. Kleyman, and R. P. Hughey Epithelial Sodium Channel Exit from the Endoplasmic Reticulum Is Regulated by a Signal within the Carboxyl Cytoplasmic Domain of the {alpha} Subunit J. Biol. Chem., November 16, 2007; 282(46): 33475 - 33483. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. C. Grifoni, K. P. Gannon, D. E. Stec, and H. A. Drummond ENaC proteins contribute to VSMC migration Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H3076 - H3086. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. L. Jernigan and H. A. Drummond Myogenic vasoconstriction in mouse renal interlobar arteries: role of endogenous beta and {gamma}ENaC Am J Physiol Renal Physiol, December 1, 2006; 291(6): F1184 - F1191. [Abstract] [Full Text] [PDF] |
||||
![]() |
X.-m. Zha, J. A. Wemmie, S. H. Green, and M. J. Welsh Acid-sensing ion channel 1a is a postsynaptic proton receptor that affects the density of dendritic spines PNAS, October 31, 2006; 103(44): 16556 - 16561. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Lin, K. J. Mann, E. Starostina, R. D. Kinser, and C. W. Pikielny A Drosophila DEG/ENaC channel subunit is required for male response to female pheromones PNAS, September 6, 2005; 102(36): 12831 - 12836. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. P. Hughey, J. B. Bruns, C. L. Kinlough, and T. R. Kleyman Distinct Pools of Epithelial Sodium Channels Are Expressed at the Plasma Membrane J. Biol. Chem., November 19, 2004; 279(47): 48491 - 48494. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. M. Hruska-Hageman, C. J. Benson, A. S. Leonard, M. P. Price, and M. J. Welsh PSD-95 and Lin-7b Interact with Acid-sensing Ion Channel-3 and Have Opposite Effects on H+-gated Current J. Biol. Chem., November 5, 2004; 279(45): 46962 - 46968. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Biasio, T. Chang, C. J. McIntosh, and F. J. McDonald Identification of Murr1 as a Regulator of the Human {delta} Epithelial Sodium Channel J. Biol. Chem., February 13, 2004; 279(7): 5429 - 5434. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Dagenais, R. Frechette, Y. Yamagata, T. Yamagata, J.-F. Carmel, M.-E. Clermont, E. Brochiero, C. Masse, and Y. Berthiaume Downregulation of ENaC activity and expression by TNF-{alpha} in alveolar epithelial cells Am J Physiol Lung Cell Mol Physiol, February 1, 2004; 286(2): L301 - L311. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. A. Weisz and J. P. Johnson Noncoordinate regulation of ENaC: paradigm lost? Am J Physiol Renal Physiol, November 1, 2003; 285(5): F833 - F842. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. B. Bruns, B. Hu, Y. J. Ahn, S. Sheng, R. P. Hughey, and T. R. Kleyman Multiple epithelial Na+ channel domains participate in subunit assembly Am J Physiol Renal Physiol, October 1, 2003; 285(4): F600 - F609. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. P. Hughey, G. M. Mueller, J. B. Bruns, C. L. Kinlough, P. A. Poland, K. L. Harkleroad, M. D. Carattino, and T. R. Kleyman Maturation of the Epithelial Na+ Channel Involves Proteolytic Processing of the {alpha}- and {gamma}-Subunits J. Biol. Chem., September 26, 2003; 278(39): 37073 - 37082. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. Bonny and B. C. Rossier Disturbances of Na/K Balance: Pseudohypoaldosteronism Revisited J. Am. Soc. Nephrol., September 1, 2002; 13(9): 2399 - 2414. [Full Text] [PDF] |
||||
![]() |
F. J. McDonald, A. H. Western, J. D. McNeil, B. C. Thomas, D. R. Olson, and P. M. Snyder Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na+ channel Am J Physiol Renal Physiol, September 1, 2002; 283(3): F431 - F436. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Kellenberger and L. Schild Epithelial Sodium Channel/Degenerin Family of Ion Channels: A Variety of Functions for a Shared Structure Physiol Rev, July 1, 2002; 82(3): 735 - 767. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Xie, M. P. Price, A. L. Berger, and M. J. Welsh DRASIC Contributes to pH-Gated Currents in Large Dorsal Root Ganglion Sensory Neurons by Forming Heteromultimeric Channels J Neurophysiol, June 1, 2002; 87(6): 2835 - 2843. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. M. Snyder The Epithelial Na+ Channel: Cell Surface Insertion and Retrieval in Na+ Homeostasis and Hypertension Endocr. Rev., April 1, 2002; 23(2): 258 - 275. [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] |
||||
![]() |
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] |
||||
![]() |
B. L. Blazer-Yost, M. Butterworth, A. D. Hartman, G. E. Parker, C. J. Faletti, W. J. Els, and S. J. Rhodes Characterization and imaging of A6 epithelial cell clones expressing fluorescently labeled ENaC subunits Am J Physiol Cell Physiol, August 1, 2001; 281(2): C624 - C632. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. L. B. Langloh, B. Berdiev, H.-L. Ji, K. Keyser, B. A. Stanton, and D. J. Benos Charged residues in the M2 region of alpha -hENaC play a role in channel conductance Am J Physiol Cell Physiol, February 1, 2000; 278(2): C277 - C291. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Jovov, A. Tousson, H.-L. Ji, D. Keeton, V. Shlyonsky, P.-J. Ripoll, C. M. Fuller, and D. J. Benos Regulation of Epithelial Na+ Channels by Actin in Planar Lipid Bilayers and in the Xenopus Oocyte Expression System J. Biol. Chem., December 31, 1999; 274(53): 37845 - 37854. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. L. Chalfant, J. S. Denton, A. L. Langloh, K. H. Karlson, J. Loffing, D. J. Benos, and B. A. Stanton The NH2 Terminus of the Epithelial Sodium Channel Contains an Endocytic Motif J. Biol. Chem., November 12, 1999; 274(46): 32889 - 32896. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Eskandari, P. M. Snyder, M. Kreman, G. A. Zampighi, M. J. Welsh, and E. M. Wright Number of Subunits Comprising the Epithelial Sodium Channel J. Biol. Chem., September 17, 1999; 274(38): 27281 - 27286. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. J. Ahn, D. R. Brooker, F. Kosari, B. J. Harte, J. Li, S. A. Mackler, and T. R. Kleyman Cloning and functional expression of the mouse epithelial sodium channel Am J Physiol Renal Physiol, July 1, 1999; 277(1): F121 - F129. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. S. Prince and M. J. Welsh Effect of subunit composition and Liddle's syndrome mutations on biosynthesis of ENaC Am J Physiol Cell Physiol, June 1, 1999; 276(6): C1346 - C1351. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Firsov, M. Robert-Nicoud, S. Gruender, L. Schild, and B. C. Rossier Mutational Analysis of Cysteine-rich Domains of the Epithelium Sodium Channel (ENaC). IDENTIFICATION OF CYSTEINES ESSENTIAL FOR CHANNEL EXPRESSION AT THE CELL SURFACE J. Biol. Chem., January 29, 1999; 274(5): 2743 - 2749. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Cheng, L. S. Prince, P. M. Snyder, and M. J. Welsh Assembly of the Epithelial Na+ Channel Evaluated Using Sucrose Gradient Sedimentation Analysis J. Biol. Chem., August 28, 1998; 273(35): 22693 - 22700. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. M. Snyder, C. Cheng, L. S. Prince, J. C. Rogers, and M. J. Welsh Electrophysiological and Biochemical Evidence That DEG/ENaC Cation Channels Are Composed of Nine Subunits J. Biol. Chem., January 9, 1998; 273(2): 681 - 684. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. A. Weisz, J.-M. Wang, R. S. Edinger, and J. P. Johnson Non-coordinate Regulation of Endogenous Epithelial Sodium Channel (ENaC) Subunit Expression at the Apical Membrane of A6 Cells in Response to Various Transporting Conditions J. Biol. Chem., December 15, 2000; 275(51): 39886 - 39893. [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] |
||||
![]() |
C. P. Thomas, R. W. Loftus, K. Z. Liu, and O. A. Itani Genomic organization of the 5' end of human beta -ENaC and preliminary characterization of its promoter Am J Physiol Renal Physiol, May 1, 2002; 282(5): F898 - F909. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |