%0 Journal Article %A Chi-Wei Tien %A Bin Yu %A Mengjia Huang %A Karolina P. Stepien %A Kyoko Sugita %A Xiaoyu Xie %A Liping Han %A Philippe P. Monnier %A Mei Zhen %A Josep Rizo %A Shangbang Gao %A Shuzo Sugita %T Open syntaxin overcomes synaptic transmission defects in diverse C. elegans exocytosis mutants %D 2020 %R 10.1101/2020.01.10.901835 %J bioRxiv %P 2020.01.10.901835 %X 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 Ca2+ 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. %U https://www.biorxiv.org/content/biorxiv/early/2020/01/11/2020.01.10.901835.full.pdf