Open syntaxin overcomes synaptic transmission defects in diverseC. elegansexocytosis mutants

Summary Assembly of SNARE complexes that mediate neurotransmitter release requires opening of a ‘closed’ conformation of UNC-64/syntaxin. Rescue of unc-13/Munc13 phenotypes by overexpressed open UNC-64/syntaxin suggested a specific function of UNC-13/Munc13 in opening UNC-64/ syntaxin. Here, we revisit the effects of open unc-64 /syntaxin by generating knockin (KI) worms. The KI animals exhibited enhanced spontaneous and evoked exocytosis compared to wild-type animals. Unexpectedly, the open syntaxin KI partially suppressed exocytosis defects of various mutants, including snt-1 /synaptotagmin, unc-2/ P/Q/N-type Ca 2+ channel alpha-subunit, and unc-31/ CAPS in addition to unc-13/ Munc13 and unc-10/ RIM, and enhanced exocytosis in tom-1/ Tomosyn mutants. However, open syntaxin aggravated the defects of unc-18/ Munc18 mutants. Correspondingly, open syntaxin partially bypasses the requirement of Munc13 but not Munc18 for liposome fusion. Our results show that facilitating opening of syntaxin enhances exocytosis in a wide range of genetic backgrounds, and may provide a general means to enhance synaptic transmission in normal and disease states.