title: SNARE force synchronizes synaptic vesicle fusion and controls the kinetics of quantal synaptic transmission.
abstract: Neuronal communication relies on rapid and discrete intercellular signaling but neither the molecular mechanisms of the exocytotic machinery that define the timing of the action potential-evoked response nor those controlling the kinetics of transmitter release from single synaptic vesicles are known. Here, we investigate how interference with the putative force transduction between the complex-forming SNARE (soluble N-ethylamide-sensitive factor attachment protein receptor) domain and the transmembrane anchor of synaptobrevin II (SybII) affects action potential-evoked currents and spontaneous, quantal transmitter release at mouse hippocampal synapses. The results indicate that SybII-generated membrane stress effectively determines the kinetics of the action potential-evoked response and show that SNARE force modulates the concentration profile of cleft glutamate by controlling the rate of transmitter release from the single synaptic vesicle. Thus, multiple SybII actions determine the exquisite temporal regulation of neuronal signaling.
authors.affiliation: University of Saarland, Medical Faculty, Institute for Physiology, D-66424 Homburg, Germany.
authors.forename: Raul E
authors.initials: RE
authors.lastname: Guzman
authors.forename: Yvonne N
authors.initials: YN
authors.lastname: Schwarz
authors.forename: Jens
authors.initials: J
authors.lastname: Rettig
authors.forename: Dieter
authors.initials: D
authors.lastname: Bruns
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D004558:Electric Stimulation; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D008561:Membrane Fusion / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D055369:Miniature Postsynaptic Potentials / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D050600:SNARE Proteins / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism*; D013997:Time Factors; D050988:Vesicle-Associated Membrane Protein 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D050600:SNARE Proteins; D050988:Vesicle-Associated Membrane Protein 2; C494808:vesicle-associated membrane protein 2, mouse