Open syntaxin overcomes exocytosis defects of diverse mutants in C. elegans

Chi-Wei Tien, Bin Yu, Mengjia Huang, Karolina P. Stepien, Kyoko Sugita, Xiaoyu Xie, Liping Han, Philippe P. Monnier, Mei Zhen, Josep Rizo (), Shangbang Gao () and Shuzo Sugita ()
Additional contact information
Chi-Wei Tien: University Health Network
Bin Yu: Huazhong University of Science and Technology
Mengjia Huang: University Health Network
Karolina P. Stepien: University of Texas Southwestern Medical Center
Kyoko Sugita: University Health Network
Xiaoyu Xie: University Health Network
Liping Han: Dalian Medical University
Philippe P. Monnier: University of Toronto
Mei Zhen: University of Toronto
Josep Rizo: University of Texas Southwestern Medical Center
Shangbang Gao: Huazhong University of Science and Technology
Shuzo Sugita: University Health Network

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: Abstract 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 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 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.

Date: 2020
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DOI: 10.1038/s41467-020-19178-x

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