Assembly of SNARE complexes that mediate neurotransmitter release requires opening of a 'closed' conformation of UNC-64/syntaxin. Rescue of
unc-13/Munc13 mutant 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 exhibit enhanced spontaneous and evoked exocytosis compared to WT animals. Unexpectedly, the open syntaxin KI partially suppresses exocytosis defects of various mutants, including
snt-1/synaptotagmin,
unc-2/P/Q/N-type Ca<sup>2+</sup> 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 aggravates 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.