SNARE complex oligomerization by synaphin/complexin is essential for synaptic vesicle exocytosis

Synaphin/complexin is a cytosolic protein that preferentially binds to synt axin within the SNARE complex. We find that synaphin promotes SNAREs to for m pre-complexes that oligomerize into higher order structures. A peptide fr om the central, syntaxin binding domain of synaphin competitively inhibits these two proteins from interacting and prevents SNARE complexes from oligo merizing. Injection of this peptide into squid giant presynaptic terminals inhibited neurotransmitter release at a late prefusion step of synaptic ves icle exocytosis. We propose that oligomerization of SNARE complexes into a higher order structure creates a SNARE scaffold for efficient, regulated fu sion of synaptic vesicles.