QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 18, Issue 6, 2037-2046, June 2007

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E07-01-0049v1 18/6/2037    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Siddiqui, T. J. Articles by Fasshauer, D. Search for Related Content PubMed PubMed Citation Articles by Siddiqui, T. J. Articles by Fasshauer, D.

Determinants of Synaptobrevin Regulation in Membranes

Tabrez J. Siddiqui^*,, Olga Vites^*,, Alexander Stein^*, Rainer Heintzmann^,||, Reinhard Jahn^*, and Dirk Fasshauer^*

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

Submitted January 24, 2007; Accepted March 2, 2007
Monitoring Editor: Patrick Brennwald

Neuronal exocytosis is driven by the formation of SNARE complexes between synaptobrevin 2 on synaptic vesicles and SNAP-25/syntaxin 1 on the plasma membrane. It has remained controversial, however, whether SNAREs are constitutively active or whether they are down-regulated until fusion is triggered. We now show that synaptobrevin in proteoliposomes as well as in purified synaptic vesicles is constitutively active. Potential regulators such as calmodulin or synaptophysin do not affect SNARE activity. Substitution or deletion of residues in the linker connecting the SNARE motif and transmembrane region did not alter the kinetics of SNARE complex assembly or of SNARE-mediated fusion of liposomes. Remarkably, deletion of C-terminal residues of the SNARE motif strongly reduced fusion activity, although the overall stability of the complexes was not affected. We conclude that although complete zippering of the SNARE complex is essential for membrane fusion, the structure of the adjacent linker domain is less critical, suggesting that complete SNARE complex assembly not only connects membranes but also drives fusion.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Present addresses: Brain Research Centre, Koerner F149, 2211 Wesbrook Mall, University of British Columbia, Vancouver V6T 2B5, Canada;

Molecular NeuroPathology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, WC2A 3PX, United Kingdom;

^|| King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, London SE1 1UL, United Kingdom.

Address correspondence to: Dirk Fasshauer (dfassha{at}gwdg.de).

This article has been cited by other articles:

				M. Bretou, C. Anne, and F. Darchen A Fast Mode of Membrane Fusion Dependent on Tight SNARE Zippering J. Neurosci., August 20, 2008; 28(34): 8470 - 8476. [Abstract] [Full Text] [PDF]

				E. Fdez, T. A. Jowitt, M.-C. Wang, M. Rajebhosale, K. Foster, J. Bella, C. Baldock, P. G. Woodman, and S. Hilfiker A Role for Soluble N-Ethylmaleimide-sensitive Factor Attachment Protein Receptor Complex Dimerization during Neurosecretion Mol. Biol. Cell, August 1, 2008; 19(8): 3379 - 3389. [Abstract] [Full Text] [PDF]