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J Neurophysiol. 2014 Sep 15;112(6):1559-65. doi: 10.1152/jn.00340.2014. Epub 2014 Jun 18.

Synaptobrevin 1 mediates vesicle priming and evoked release in a subpopulation of hippocampal neurons.

Author information

1
Neuroscience Research Center and NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, Berlin, Germany.
2
Neuroscience Research Center and NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, Berlin, Germany christian.rosenmund@charite.de.

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.

KEYWORDS:

SNARE; neurotransmitter release; release probability; short-term plasticity; spontaneous release

PMID:
24944211
DOI:
10.1152/jn.00340.2014
[Indexed for MEDLINE]
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