Syntaxin 1A interacts with multiple exocytic proteins to regulate neurotransmitter release in vivo

Biochemical studies suggest that syntaxin 1A participates in multiple prote in-protein interactions in the synaptic terminal, but the in vivo significa nce of these interactions is poorly understood. We used a targeted mutagene sis approach to eliminate specific syntaxin binding interactions and demons trate that Drosophila syntaxin 1A plays multiple regulatory roles in neurot ransmission in vivo. Syntaxin mutations that eliminate ROP/Munc-18 binding display increased neurotransmitter release, suggesting that ROP inhibits ne urosecretion through its interaction with syntaxin. Syntaxin mutations that block Ca2+ channel binding also cause an increase in neurotransmitter rele ase, suggesting that syntaxin normally functions in inhibiting Ca2+ channel opening. Additionally, we identify and characterize a syntaxin Ca2+ effect or domain, which may spatially organize the Ca2+ channel, cysteine string p rotein, and synaptotagmin for effective excitation-secretion coupling in th e presynaptic terminal.