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Publication : An Electrostatic Energy Barrier for SNARE-Dependent Spontaneous and Evoked Synaptic Transmission.

First Author  Ruiter M Year  2019
Journal  Cell Rep Volume  26
Issue  9 Pages  2340-2352.e5
PubMed ID  30811985 Mgi Jnum  J:299223
Mgi Id  MGI:6488821 Doi  10.1016/j.celrep.2019.01.103
Citation  Ruiter M, et al. (2019) An Electrostatic Energy Barrier for SNARE-Dependent Spontaneous and Evoked Synaptic Transmission. Cell Rep 26(9):2340-2352.e5
abstractText  Information transfer across CNS synapses depends on the very low basal vesicle fusion rate and the ability to rapidly upregulate that rate upon Ca(2+) 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 approximately 35 positive charges to the fusion machine. Within an electrostatic model for triggering, the Ca(2+) sensor synaptotagmin-1 contributes approximately 18 charges by binding Ca(2+), 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.
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