title: Synaptobrevin 1 mediates vesicle priming and evoked release in a subpopulation of hippocampal neurons.
abstract: The core machinery of synaptic vesicle fusion consists of three soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins, the two t-SNAREs at the plasma membrane (SNAP-25, Syntaxin 1) and the vesicle-bound v-SNARE synaptobrevin 2 (VAMP2). Formation of the trans-oriented four-α-helix bundle between these SNAREs brings vesicle and plasma membrane in close proximity and prepares the vesicle for fusion. The t-SNAREs are thought to be necessary for vesicle fusion. Whether the v-SNAREs are required for fusion is still unclear, as substantial vesicle priming and spontaneous release activity remain in mammalian mass-cultured synaptobrevin/cellubrevin-deficient neurons. Using the autaptic culture system from synaptobrevin 2 knockout neurons of mouse hippocampus, we found that the majority of cells were devoid of any evoked or spontaneous release and had no measurable readily releasable pool. A small subpopulation of neurons, however, displayed release, and their release activity correlated with the presence and amount of v-SNARE synaptobrevin 1 expressed. Comparison of synaptobrevin 1 and 2 in rescue experiments demonstrates that synaptobrevin 1 can substitute for the other v-SNARE, but with a lower efficiency in neurotransmitter release probability. Release activity in synaptobrevin 2-deficient mass-cultured neurons was massively reduced by a knockdown of synaptobrevin 1, demonstrating that synaptobrevin 1 is responsible for the remaining release activity. These data support the hypothesis that both t- and v-SNAREs are absolutely required for vesicle priming and evoked release and that differential expression of SNARE paralogs can contribute to differential synaptic coding in the brain.
authors.affiliation: Neuroscience Research Center and NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Zimmermann
authors.affiliation: Neuroscience Research Center and NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Trimbuch
authors.affiliation: Neuroscience Research Center and NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, Berlin, Germany christian.rosenmund@charite.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Rosenmund
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005089:Exocytosis; D005260:Female; D006624:Hippocampus / Q000166:cytology; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000502:physiology; D050987:Vesicle-Associated Membrane Protein 1 / Q000235:genetics / Q000378:metabolism*; D050988:Vesicle-Associated Membrane Protein 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D050987:Vesicle-Associated Membrane Protein 1; D050988:Vesicle-Associated Membrane Protein 2; C494771:vesicle-associated membrane protein 1, mouse; C494808:vesicle-associated membrane protein 2, mouse
keywords: SNARE; neurotransmitter release; release probability; short-term plasticity; spontaneous release