Complexin maintains vesicles in the primed state in C. elegans.

Complexin binds the SNARE complex at synapses and regulates exocytosis, but genetic studies indicate contradictory roles: in flies it predominantly inhibits synaptic vesicle fusion, whereas in mice it promotes evoked responses. Here we characterize the complexin mutant in the nematode Caenorhabditis elegans and reveal bipolar functions in neurotransmission: complexin inhibits spontaneous fusion of synaptic vesicles but is also essential for evoked responses. Complexin mutants exhibit a doubling of vesicle fusion in the absence of extracellular calcium. Even more profoundly, mutants exhibit an almost complete loss of evoked responses, and current amplitudes are reduced by 94%. One possible interpretation is that complexin is required for the stabilization of docked vesicles and that, in its absence, vesicles may fuse or undock from the plasma membrane. Consistent with this hypothesis, docked synaptic vesicles are reduced by 70% in complexin-1 mutants. These data suggest that the main function of complexin is to maintain the docked state both by inhibiting fusion and by promoting priming.