DISRUPTION OF SYNTAXIN-MEDIATED PROTEIN INTERACTIONS BLOCKS NEUROTRANSMITTER SECRETION

The membrane protein syntaxin participates in several protein-protein interactions that have been implicated in neurotransmitter release. To probe the physiological importance of these interactions, we microinj ected into the squid giant presynaptic terminal botulinum toxin C1, wh ich cleaves syntaxin, and the H3 domain of syntaxin, which mediates bi nding to other proteins, Both reagents inhibited synaptic transmission yet did not affect the number or distribution of synaptic vesicles at the presynaptic active zone. Recombinant H3 domain inhibited the inte ractions between syntaxin and SNAP-25 that underlie the formation of s table SNARE complexes in vitro. These data support the notion that syn taxin-mediated SNARE complexes are necessary for docked synaptic vesic les to fuse.