The stability of the primed pool of synaptic vesicles and the clamping of spontaneous neurotransmitter release rely on the integrity of the C-terminal half of the SNARE domain of syntaxin-1A
- PMID: 38512129
- PMCID: PMC10957171
- DOI: 10.7554/eLife.90775
The stability of the primed pool of synaptic vesicles and the clamping of spontaneous neurotransmitter release rely on the integrity of the C-terminal half of the SNARE domain of syntaxin-1A
Abstract
The SNARE proteins are central in membrane fusion and, at the synapse, neurotransmitter release. However, their involvement in the dual regulation of the synchronous release while maintaining a pool of readily releasable vesicles remains unclear. Using a chimeric approach, we performed a systematic analysis of the SNARE domain of STX1A by exchanging the whole SNARE domain or its N- or C-terminus subdomains with those of STX2. We expressed these chimeric constructs in STX1-null hippocampal mouse neurons. Exchanging the C-terminal half of STX1's SNARE domain with that of STX2 resulted in a reduced RRP accompanied by an increased release rate, while inserting the C-terminal half of STX1's SNARE domain into STX2 leads to an enhanced priming and decreased release rate. Additionally, we found that the mechanisms for clamping spontaneous, but not for Ca2+-evoked release, are particularly susceptible to changes in specific residues on the outer surface of the C-terminus of the SNARE domain of STX1A. Particularly, mutations of D231 and R232 affected the fusogenicity of the vesicles. We propose that the C-terminal half of the SNARE domain of STX1A plays a crucial role in the stabilization of the RRP as well as in the clamping of spontaneous synaptic vesicle fusion through the regulation of the energetic landscape for fusion, while it also plays a covert role in the speed and efficacy of Ca2+-evoked release.
Keywords: SNARE complex; evoked release; exocytosis; mouse; neuroscience; neurotransmitter release; spontaneous release; synapse.
© 2023, Salazar Lázaro et al.
Conflict of interest statement
AS, TT, GV, CR No competing interests declared
Figures
Update of
- doi: 10.1101/2023.07.06.547909
- doi: 10.7554/eLife.90775.1
- doi: 10.7554/eLife.90775.2
Similar articles
-
SNAP25 disease mutations change the energy landscape for synaptic exocytosis due to aberrant SNARE interactions.Elife. 2024 Feb 27;12:RP88619. doi: 10.7554/eLife.88619. Elife. 2024. PMID: 38411501 Free PMC article.
-
Reexamination of N-terminal domains of syntaxin-1 in vesicle fusion from central murine synapses.Elife. 2021 Aug 24;10:e69498. doi: 10.7554/eLife.69498. Elife. 2021. PMID: 34427183 Free PMC article.
-
Distinct Functions of Syntaxin-1 in Neuronal Maintenance, Synaptic Vesicle Docking, and Fusion in Mouse Neurons.J Neurosci. 2016 Jul 27;36(30):7911-24. doi: 10.1523/JNEUROSCI.1314-16.2016. J Neurosci. 2016. PMID: 27466336 Free PMC article.
-
Neurotransmitter release: the last millisecond in the life of a synaptic vesicle.Neuron. 2013 Oct 30;80(3):675-90. doi: 10.1016/j.neuron.2013.10.022. Neuron. 2013. PMID: 24183019 Free PMC article. Review.
-
TRP Channel Trafficking.In: Liedtke WB, Heller S, editors. TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades. Boca Raton (FL): CRC Press/Taylor & Francis; 2007. Chapter 23. In: Liedtke WB, Heller S, editors. TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades. Boca Raton (FL): CRC Press/Taylor & Francis; 2007. Chapter 23. PMID: 21204515 Free Books & Documents. Review.
References
-
- Arancillo M, Min SW, Gerber S, Münster-Wandowski A, Wu YJ, Herman M, Trimbuch T, Rah JC, Ahnert-Hilger G, Riedel D, Südhof TC, Rosenmund C. Titration of Syntaxin1 in mammalian synapses reveals multiple roles in vesicle docking, priming, and release probability. The Journal of Neuroscience. 2013;33:16698–16714. doi: 10.1523/JNEUROSCI.0187-13.2013. - DOI - PMC - PubMed
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Miscellaneous