An electrostatic energy barrier for SNARE-dependent spontaneous and evoked synaptic transmission

Summary - 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...

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Bibliographic Details
Main Authors: Ruiter, Marvin (Author) , Malsam, Andrea (Author) , Malsam, Jörg (Author) , Söllner, Thomas (Author)
Format: Article (Journal)
Language:English
Published: 26 February 2019
In: Cell reports
Year: 2019, Volume: 26, Issue: 9, Pages: 2340-2352
ISSN:2211-1247
DOI:10.1016/j.celrep.2019.01.103
Online Access:Verlag, Volltext: https://doi.org/10.1016/j.celrep.2019.01.103
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S2211124719301408
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Author Notes:Marvin Ruiter, Anna Kádková, Andrea Scheutzow, Jörg Malsam, Thomas H. Söllner, Jakob B. Sørensen
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Summary:Summary - 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.
Item Description:Gesehen am 08.07.2019
Physical Description:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2019.01.103