1. Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, Utah 84112-0840, USA
2. These authors contributed equally to this work

Correspondence to: Erik M. Jorgensen Correspondence and requests for materials should be addressed to E.M.J. (e-mail: Email: jorgensen@biology.utah.edu)

Abstract

The priming step of synaptic vesicle exocytosis is thought to require the formation of the SNARE complex, which comprises the proteins synaptobrevin, SNAP-25 and syntaxin^{1, 2, 3}. In solution syntaxin adopts a default, closed configuration that is incompatible with formation of the SNARE complex⁴. Specifically, the amino terminus of syntaxin binds the SNARE motif and occludes interactions with the other SNARE proteins. The N terminus of syntaxin also binds the presynaptic protein UNC-13 (ref. 5). Studies in mouse, Drosophila and Caenorhabditis elegans suggest that UNC-13 functions at a post-docking step of exocytosis, most likely during synaptic vesicle priming^{6, 7, 8}. Therefore, UNC-13 binding to the N terminus of syntaxin may promote the open configuration of syntaxin⁹. To test this model, we engineered mutations into C. elegans syntaxin that cause the protein to adopt the open configuration constitutively⁴. Here we demonstrate that the open form of syntaxin can bypass the requirement for UNC-13 in synaptic vesicle priming. Thus, it is likely that UNC-13 primes synaptic vesicles for fusion by promoting the open configuration of syntaxin.