Reexamination of N-terminal domains of Syntaxin-1 in vesicle fusion from central murine synapses
- Charité Universitätsmedizin, Germany
- Charité Universitätsmedizin Berlin, Germany
Abstract
Syntaxin-1 (STX1) and Munc18-1 are two requisite components of synaptic vesicular release machinery, so much so synaptic transmission cannot proceed in their absence. They form a tight complex through two major binding modes: through STX1's N-peptide and through STX's closed conformation driven by its Habc- domain. However, physiological roles of these two reportedly different binding modes in synapses are still controversial. Here we characterized the roles of STX1's N-peptide, Habc-domain, and open conformation with and without N-peptide deletion using our STX1-null mouse model system and exogenous reintroduction of STX1A mutants. We show, on the contrary to the general view, that the Habc-domain is absolutely required and N-peptide is dispensable for synaptic transmission. However, STX1A's N-peptide plays a regulatory role, particularly in the Ca2+-sensitivity and the short-term plasticity of vesicular release, whereas STX1's open-conformation governs the vesicle fusogenicity. Strikingly, we also show neurotransmitter release still proceeds when the two interaction modes between STX1A and Munc18-1 are presumably intervened, necessitating a refinement of the conceptualization of STX1A-Munc18-1 interaction.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. We uploaded source data files which show summary tables of mean, SEM, median, number of independent cultures, number of independent measurements, real p value for each test performed, and statistical test used for each separate figure.
Article and author information
Author details
Marisa M Brockmann
Christian Rosenmund
Funding
Deutsche Forschungsgemeinschaft (SFB958,TRR186)
- Christian Rosenmund
Deutsche Forschungsgemeinschaft (Reinhart Koselleck Projects)
- Christian Rosenmund
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures for animal maintenance and experiments were in accordance with the regulations of and approved by the animal welfare committee of Charité-Universitätsmedizin and the Berlin state government Agency for Health and Social Services under license number T0220/09. The generation of STX1-null mouse line was described previously (Arancillo et al. 2013, Vardar et al. 2016).
Copyright
© 2021, Vardar et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Reexamination of N-terminal domains of Syntaxin-1 in vesicle fusion from central murine synapses
eLife 10:e69498.
https://doi.org/10.7554/eLife.69498
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