An open form of syntaxin bypasses the requirement for UNC-13 in vesicle priming

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(1-3). In solution syntaxin adopts a default, closed configuration that is incompatible with formation of the SNARE complex(4). 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(6-8). Therefore, UNC-13 binding to the N terminus of syntaxin may promote the open configuration of syntaxin(9). To test this model, we engineered mutations into C. elegans syntaxin that cause the protein to adopt the open configuration constitutively(4). 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.