JBC Origene Your Gene Company

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M210772200 on January 30, 2003

J. Biol. Chem., Vol. 278, Issue 15, 12796-12804, April 11, 2003
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
278/15/12796    most recent
M210772200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Condliffe, S. B.
Right arrow Articles by Zhang, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Condliffe, S. B.
Right arrow Articles by Zhang, H.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Syntaxin 1A Regulates ENaC via Domain-specific Interactions*

Steven B. CondliffeDagger §, Marcelo D. Carattino||, Raymond A. FrizzellDagger **, and Hui ZhangDagger **

From the Dagger  Department of Cell Biology and Physiology and the  Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261

The epithelial sodium channel (ENaC) is a heterotrimeric protein responsible for Na+ absorption across the apical membranes of several absorptive epithelia. The rate of Na+ absorption is governed in part by regulated membrane trafficking mechanisms that control the apical membrane ENaC density. Previous reports have implicated a role for the t-SNARE protein, syntaxin 1A (S1A), in the regulation of ENaC current (INa). In the present study, we examine the structure-function relations influencing S1A-ENaC interactions. In vitro pull-down assays demonstrated that S1A directly interacts with the C termini of the alpha -, beta -, and gamma -ENaC subunits but not with the N terminus of any ENaC subunit. The H3 domain of S1A is the critical motif mediating S1A-ENaC binding. Functional studies in ENaC expressing Xenopus oocytes revealed that deletion of the H3 domain of co-expressed S1A eliminated its inhibition of INa, and acute injection of a GST-H3 fusion protein into ENaC expressing oocytes inhibited INa to the same extent as S1A co-expression. In cell surface ENaC labeling experiments, reductions in plasma membrane ENaC accounted for the H3 domain inhibition of INa. Individually substituting C terminus-truncated alpha -, beta -, or gamma -ENaC subunits for their wild-type counterparts reversed the S1A-induced inhibition of INa, and oocytes expressing ENaC comprised of three C terminus-truncated subunits showed no S1A inhibition of INa. C terminus truncation or disruption of the C terminus beta -subunit PY motif increases INa by interfering with ENaC endocytosis. In contrast to subunit truncation, a beta -ENaC PY mutation did not relieve S1A inhibition of INa, suggesting that S1A does not perturb Nedd4 interactions that lead to ENaC endocytosis/degradation. This study provides support for the concept that S1A inhibits ENaC-mediated Na+ transport by decreasing cell surface channel number via direct protein-protein interactions at the ENaC C termini.

* This work was supported by National Institutes of Health Grant DK54814 and Cystic Fibrosis Foundation Grants FRIZZE99G0 and FRIZZE97RO.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Recipient of a postdoctoral fellowship from the Cystic Fibrosis Foundation.

|| Recipient of a postdoctoral fellowships from the Pennsylvania-Delaware Affiliate of the American Heart Association.

** To whom correspondence may be addressed: Dept. of Cell Biology and Physiology, University of Pittsburgh School of Medicine, S362 BST, 3500 Terrace St., Pittsburgh, PA 15261. Tel.: 412-648-9498; Fax: 412-648-8330; E-mail: frizzell@pitt.edu or Zhangh{at}pitt.edu.

Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
W. G. Hill, M. B. Butterworth, H. Wang, R. S. Edinger, J. Lebowitz, K. W. Peters, R. A. Frizzell, and J. P. Johnson
The Epithelial Sodium Channel (ENaC) Traffics to Apical Membrane in Lipid Rafts in Mouse Cortical Collecting Duct Cells
J. Biol. Chem., December 28, 2007; 282(52): 37402 - 37411.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Zhang, B. Z. Schmidt, F. Sun, S. B. Condliffe, M. B. Butterworth, R. T. Youker, J. L. Brodsky, M. Aridor, and R. A. Frizzell
Cysteine String Protein Monitors Late Steps in Cystic Fibrosis Transmembrane Conductance Regulator Biogenesis
J. Biol. Chem., April 21, 2006; 281(16): 11312 - 11321.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. S. Edinger, J. Yospin, C. Perry, T. R. Kleyman, and J. P. Johnson
Regulation of Epithelial Na+ Channels (ENaC) by Methylation: A NOVEL METHYLTRANSFERASE STIMULATES ENaC ACTIVITY
J. Biol. Chem., April 7, 2006; 281(14): 9110 - 9117.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
P. M. Snyder
Minireview: Regulation of Epithelial Na+ Channel Trafficking
Endocrinology, December 1, 2005; 146(12): 5079 - 5085.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
M. B. Butterworth, R. A. Frizzell, J. P. Johnson, K. W. Peters, and R. S. Edinger
PKA-dependent ENaC trafficking requires the SNARE-binding protein complexin
Am J Physiol Renal Physiol, November 1, 2005; 289(5): F969 - F977.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Cui, Y. Kang, Y. He, Y.-M. Leung, H. Xie, E. A. Pasyk, X. Gao, L. Sheu, J. B. Hansen, P. Wahl, et al.
H3 Domain of Syntaxin 1A Inhibits KATP Channels by Its Actions on the Sulfonylurea Receptor 1 Nucleotide-Binding Folds-1 and -2
J. Biol. Chem., December 17, 2004; 279(51): 53259 - 53265.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Lebowitz, R. S. Edinger, B. An, C. J. Perry, S. Onate, T. R. Kleyman, and J. P. Johnson
I{kappa}B Kinase-{beta} (IKK{beta}) Modulation of Epithelial Sodium Channel Activity
J. Biol. Chem., October 1, 2004; 279(40): 41985 - 41990.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
B. K. Berdiev, B. Jovov, W. C. Tucker, A. P. Naren, C. M. Fuller, E. R. Chapman, and D. J. Benos
ENaC subunit-subunit interactions and inhibition by syntaxin 1A
Am J Physiol Renal Physiol, June 1, 2004; 286(6): F1100 - F1106.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. B. Condliffe, H. Zhang, and R. A. Frizzell
Syntaxin 1A Regulates ENaC Channel Activity
J. Biol. Chem., March 12, 2004; 279(11): 10085 - 10092.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
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]

Home page
 Am. J. Physiol. Cell Physiol.Home page
J. G. Duman and J. G. Forte
What is the role of SNARE proteins in membrane fusion?
Am J Physiol Cell Physiol, August 1, 2003; 285(2): C237 - C249.
[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 
Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.