An Electrostatic Energy Barrier for SNARE-Dependent Spontaneous and Evoked Synaptic Transmission
- PMID: 30811985
- DOI: 10.1016/j.celrep.2019.01.103
An Electrostatic Energy Barrier for SNARE-Dependent Spontaneous and Evoked Synaptic Transmission
Abstract
Information transfer across CNS synapses depends on the very low basal vesicle fusion rate and the ability to rapidly upregulate that rate upon Ca2+ influx. We show that local electrostatic repulsion participates in creating an energy barrier, which limits spontaneous synaptic transmission. The barrier amplitude is increased by negative charges and decreased by positive charges on the SNARE-complex surface. Strikingly, the effect of charges on the barrier is additive and this extends to evoked transmission, but with a shallower charge dependence. Action potential-driven synaptic release is equivalent to the abrupt addition of ∼35 positive charges to the fusion machine. Within an electrostatic model for triggering, the Ca2+ sensor synaptotagmin-1 contributes ∼18 charges by binding Ca2+, while also modulating the fusion barrier at rest. Thus, the energy barrier for synaptic vesicle fusion has a large electrostatic component, allowing synaptotagmin-1 to act as an electrostatic switch and modulator to trigger vesicle fusion.
Keywords: SNAP-25; SNARE-complex; autaptic neuron; energy barrier; glutamatergic synapse; mathematical modeling; membrane fusion; spontaneous release; synaptic transmission; synaptotagmin-1.
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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.
-
Interactions Between SNAP-25 and Synaptotagmin-1 Are Involved in Vesicle Priming, Clamping Spontaneous and Stimulating Evoked Neurotransmission.J Neurosci. 2016 Nov 23;36(47):11865-11880. doi: 10.1523/JNEUROSCI.1011-16.2016. J Neurosci. 2016. PMID: 27881774 Free PMC article.
-
SNARE protein recycling by αSNAP and βSNAP supports synaptic vesicle priming.Neuron. 2010 Nov 4;68(3):473-87. doi: 10.1016/j.neuron.2010.09.019. Neuron. 2010. PMID: 21040848
-
Roles of SNARE proteins and synaptotagmin I in synaptic transmission: studies at the Drosophila neuromuscular synapse.Neurosignals. 2003 Jan-Feb;12(1):13-30. doi: 10.1159/000068912. Neurosignals. 2003. PMID: 12624525 Review.
-
Models of synaptotagmin-1 to trigger Ca2+ -dependent vesicle fusion.FEBS Lett. 2018 Nov;592(21):3480-3492. doi: 10.1002/1873-3468.13193. Epub 2018 Jul 30. FEBS Lett. 2018. PMID: 30004579 Review.
Cited by
-
SNARE complex alters the interactions of the Ca2+ sensor synaptotagmin 1 with lipid bilayers.Biophys J. 2021 Feb 16;120(4):642-661. doi: 10.1016/j.bpj.2020.12.025. Epub 2021 Jan 14. Biophys J. 2021. PMID: 33453271 Free PMC article.
-
Synaptic Secretion and Beyond: Targeting Synapse and Neurotransmitters to Treat Neurodegenerative Diseases.Oxid Med Cell Longev. 2022 Jul 25;2022:9176923. doi: 10.1155/2022/9176923. eCollection 2022. Oxid Med Cell Longev. 2022. PMID: 35923862 Free PMC article. Review.
-
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.Elife. 2024 Mar 21;12:RP90775. doi: 10.7554/eLife.90775. Elife. 2024. PMID: 38512129 Free PMC article.
-
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.
-
Post-tetanic potentiation lowers the energy barrier for synaptic vesicle fusion independently of Synaptotagmin-1.Elife. 2020 Aug 24;9:e55713. doi: 10.7554/eLife.55713. Elife. 2020. PMID: 32831174 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Miscellaneous
