Syntaphilin: A syntaxin-1 clamp that controls SNARE assembly

Syntaxin-1 is a key component of the synaptic vesicle docking/fusion machin ery that forms the SNARE complex with VAMP/synaptobrevin and SNAP-25. Ident ifying proteins that modulate SNARE complex formation is critical for under standing the molecular mechanisms underlying neurotransmitter release and i ts modulation. We have cloned and characterized a protein called syntaphili n that is selectively expressed in brain. Syntaphilin competes with SNAP-25 for binding to syntaxin-1 and inhibits SNARE complex formation by absorbin g free syntaxin-1. Transient overexpression of syntaphilin in cultured hipp ocampal neurons significantly reduces neurotransmitter release. Furthermore , introduction of syntaphilin into presynaptic superior cervical ganglion n eurons in culture inhibits synaptic transmission. These findings suggest th at syntaphilin may function as a molecular clamp that controls free syntaxi n-1 availability for the assembly of the SNARE complex, and thereby regulat es synaptic vesicle exocytosis.