Molecular Biology of the Cell click for CBE Life Science Education Page

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print December 19, 2007
Mol. Biol. Cell 10.1091/mbc.E07-05-0498

A more recent version of this article appeared on March 1, 2008
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Materials
Right arrow All Versions of this Article:
E07-05-0498v1
19/3/776    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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 Barszczewski, M.
Right arrow Articles by Jahn, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Barszczewski, M.
Right arrow Articles by Jahn, R.

Submitted on May 25, 2007
Revised on October 24, 2007
Accepted on December 10, 2007

A Novel Site of Action for {alpha}-SNAP in the SNARE Conformational Cycle Controlling Membrane Fusion

Marcin Barszczewski,* John J. Chua,* Alexander Stein,* Ulrike Winter,* Rainer Heintzmann,{dagger}{ddagger} Felipe E. Zilly,*{sect} Dirk Fasshauer,* Thorsten Lang,*|| and Reinhard Jahn*

Departments of *Neurobiology and {dagger}Molecular Biology, Max-Planck-Institute for Biophysical Chemistry, 37077 Göttingen, Germany

Monitoring Editor: Adam Linstedt

Regulated exocytosis in neurons and neuroendocrine cells requires the formation of a stable SNARE complex consisting of synaptobrevin-2/VAMP2, SNAP-25, and syntaxin 1. This complex is subsequently disassembled by the concerted action of {alpha}-SNAP and the AAA-ATPase NSF. We report that NSF inhibition causes accumulation of {alpha} -SNAP in clusters on plasma membranes. Clustering is mediated by the binding of {alpha}-SNAP to uncomplexed syntaxin since cleavage of syntaxin with botulinum neurotoxin C1 or competition using antibodies against syntaxin SNARE motif abolishes clustering. Binding of {alpha}-SNAP potently inhibits Ca2+-dependent exocytosis of secretory granules and SNARE-mediated liposome fusion. Membrane clustering and inhibition of both exocytosis and liposome fusion are counteracted by NSF but not when an {alpha}-SNAP mutant defective in NSF-activation is used. We conclude that {alpha}-SNAP inhibits exocytosis by binding to the syntaxin SNARE motif and in turn preventing SNARE assembly, revealing an unexpected site of action for {alpha}-SNAP in the SNARE cycle that drives exocytotic membrane fusion.

Present addresses: {ddagger}King’s College London, Randall Division of Cell and Molecular Biophysics, New Hunt’s House, Guy’s Campus, London SE1 1UL, United Kingdom; {sect}Department of Synthetic Organic Chemistry, Max-Planck-Institute for Coal Research, 45470 Mülheim an der Ruhr, Germany; ||LIMES-Institute, Laboratory for Membrane Biochemistry, University of Bonn, 53115 Bonn, Germany.

Address correspondence to: Reinhard Jahn (rjahn{at}gwdg.de)




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
U. Winter, X. Chen, and D. Fasshauer
A Conserved Membrane Attachment Site in {alpha}-SNAP Facilitates N-Ethylmaleimide-sensitive Factor (NSF)-driven SNARE Complex Disassembly
J. Biol. Chem., November 13, 2009; 284(46): 31817 - 31826.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. R. Rafikova, K. Melikov, C. Ramos, L. Dye, and L. V. Chernomordik
Transmembrane Protein-free Membranes Fuse into Xenopus Nuclear Envelope and Promote Assembly of Functional Pores
J. Biol. Chem., October 23, 2009; 284(43): 29847 - 29859.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
D. Bar-On, M. Gutman, A. Mezer, U. Ashery, T. Lang, and E. Nachliel
Evaluation of the Heterogeneous Reactivity of the Syntaxin Molecules on the Inner Leaflet of the Plasma Membrane
J. Neurosci., September 30, 2009; 29(39): 12292 - 12301.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2007 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.