Epithelial Sodium Channel is Regulated by Snap-23/Syntaxin 1a Interplay.
From: Center for Cell and Molecular Biology, Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, NJ 07030, USA. ssaxena@stevens.edu
Biochemical and biophysical research communications
- Publish Date: May 2006
- ISSN: 0006-291X
- Volume: 343
- Issue: 4
- Pages: 1279-85
- Medium: Print
- Language: English
- Citation (JAMA): Saxena Sunil K, George Constantine M, Pinskiy Vadim, et al. Epithelial Sodium Channel is Regulated by Snap-23/Syntaxin 1a Interplay.. Biochem. Biophys. Res. Commun. May 2006;343:1279-85
Abstract
Sodium-selective amiloride-sensitive epithelial channel (ENaC) located in the apical membrane is involved in the reabsorption of sodium in tight epithelia. The soluble N-ethylmaleimide-sensitive attachment receptors (SNAREs) mediate vesicle trafficking in a variety of cell systems. Syntaxin (a t-SNARE) has been shown to interact with and functionally regulate a number of ion channels including ENaC. In this study, we investigated the role of SNAP-23, another SNARE protein, on ENaC activity in the HT-29 colonic epithelial cell system and Xenopus oocytes. Recording of amiloride-sensitive currents in both systems suggest that SNAP-23 modulates channel function, though a much higher concentration is required to inhibit ENaC in Xenopus oocytes. The introduction of Botulinum toxin A (a neurotoxin which cleaves SNAP-23), but not Botulinum toxin B or heat-inactivated Botulinum toxin A, reversed the inhibitory effect of SNAP-23 on amiloride-sensitive currents. However, syntaxin 1A and SNAP-23 combined portray a complex scenario that suggests that this channel interacts within a quaternary complex. Synaptotagmin expression neither interacts with, nor showed any effect on amiloride-sensitive currents when co-expressed with ENaC. Pull down assays suggest mild interaction between ENaC and SNAP-23, which gets stronger in the presence of syntaxin 1A. Data further suggest that SNAP-23 possibly interacts with the N-terminal alphaENaC. These functional and biochemical approaches provide evidence for a complex relationship between ENaC and the exocytotic machinery. Our data suggest that SNARE protein interplay defines the fine regulation of sodium channel function.
Mesh Headings (Keywords): Amiloride, Animals, Botulinum Toxin Type A, Botulinum Toxins, Cell Line, Epithelial Cells, Epithelial Sodium Channel, Humans, Ion Channel Gating, Oocytes, Protein Binding, Protein Structure, Tertiary, Qb-SNARE Proteins, Qc-SNARE Proteins, Rats, Sodium Channels, Synaptotagmins, Syntaxin 1, Vesicle-Associated Membrane Protein 2, Xenopus laevis
Check for Full Text / PubMed Unique Identifier (PMID): 16581026
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