Open syntaxin overcomes synaptic transmission defects in diverse C. elegans exocytosis mutants

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, Shuzo Sugita

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Jan 11 2020

Keywords

  • exocytosis
  • Munc13/UNC-13
  • Munc18/UNC-18
  • SNARE
  • synaptotagmin
  • vesicle priming

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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