An Electrostatic Energy Barrier for SNARE-Dependent Spontaneous and Evoked Synaptic Transmission. 2019

Marvin Ruiter, and Anna Kádková, and Andrea Scheutzow, and Jörg Malsam, and Thomas H Söllner, and Jakob B Sørensen
Department of Neuroscience, Faculty of Health and Medical Sciences, 2200 Copenhagen N, University of Copenhagen, Copenhagen, Denmark.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008561 Membrane Fusion The adherence and merging of cell membranes, intracellular membranes, or artificial membranes to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. Fusion, Membrane,Fusions, Membrane,Membrane Fusions
D008959 Models, Neurological Theoretical representations that simulate the behavior or activity of the neurological system, processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. Neurologic Models,Model, Neurological,Neurologic Model,Neurological Model,Neurological Models,Model, Neurologic,Models, Neurologic
D009435 Synaptic Transmission The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES. Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013572 Synaptic Vesicles Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. Synaptic Vesicle,Vesicle, Synaptic,Vesicles, Synaptic
D050600 SNARE Proteins A superfamily of small proteins which are involved in the MEMBRANE FUSION events, intracellular protein trafficking and secretory processes. They share a homologous SNARE motif. The SNARE proteins are divided into subfamilies: QA-SNARES; QB-SNARES; QC-SNARES; and R-SNARES. The formation of a SNARE complex (composed of one each of the four different types SNARE domains (Qa, Qb, Qc, and R)) mediates MEMBRANE FUSION. Following membrane fusion SNARE complexes are dissociated by the NSFs (N-ETHYLMALEIMIDE-SENSITIVE FACTORS), in conjunction with SOLUBLE NSF ATTACHMENT PROTEIN, i.e., SNAPs (no relation to SNAP 25.) SNAP Receptor,SNARE Protein,NSF Attachment Protein Receptor,Receptor, SNAP,SNAP Receptors,SNARE,SNAREs,Soluble N-ethylmaleimide-Sensitive-Factor Attachment Protein Receptor,Target Membrane SNARE Proteins,Target SNARE Proteins,Vesicle SNARE Proteins,Vesicular SNARE Proteins,t-SNARE,tSNAREs,v-SNARE,v-SNAREs,Protein, SNARE,SNARE Proteins, Target,SNARE Proteins, Vesicle,SNARE Proteins, Vesicular,Soluble N ethylmaleimide Sensitive Factor Attachment Protein Receptor,v SNAREs
D050863 Synaptotagmin I A vesicular transport protein expressed predominately in NEURONS. Synaptotagmin helps regulate EXOCYTOSIS of SYNAPTIC VESICLES and appears to serve as a calcium sensor to trigger NEUROTRANSMITTER release. It also acts as a nerve cell receptor for certain BOTULINUM TOXINS. Synaptic Vesicle Protein p65,Synaptotagmin 1,p65 Protein (Synaptotagmin I)

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