Ablation of all synaptobrevin vSNAREs blocks evoked but not spontaneous neurotransmitter release at neuromuscular synapses

Yun Liu, Yoshie Sugiura, Thomas C. Südhof, Weichun Lin

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Synaptic transmission occurs when an action potential triggers neurotransmitter release via the fusion of synaptic vesicles with the presynaptic membrane, driven by the formation of SNARE complexes composed of the vesicular (v)-SNARE synaptobrevin and the target (t)-SNAREs Snap-25 and syntaxin-1. Neurotransmitters are also released spontaneously, independent of an action potential, through the fusion of synaptic vesicles with the presynaptic membrane. The major neuronal vSNAREs, synaptobrevin-1 and synaptobrevin-2, are expressed at the developing neuromuscular junction (NMJ) in mice, but their specific roles in NMJ formation and function remain unclear. Here, we examine the NMJs in mutant mouse embryos lacking either synaptobrevin 1 (Syb1lew/lew) or synaptobrevin 2 (Syb2-/-), and those lacking both (Syb1lew/lewSyb2-/-). We found that, compared with controls: (1) the number and size of NMJs was markedly increased in Syb2-/- and Syb1lew/lewSyb2-/- mice, but not in Syb1lew/lew mice; (2) synaptic vesicle density was markedly reduced in Syb1lew/lewSyb2-/NMJs; and (3) evoked neurotransmission was markedly reduced in Syb2-/- NMJs and completely abolished in Syb1lew/lewSyb2-/- NMJs. Surprisingly, however, spontaneous neurotransmission persists in the absence of both Syb1 and Syb2. Furthermore, spontaneous neurotransmission remains constant in Syb1lew/lewSyb2-/- NMJs despite changing Ca 2+ levels. These findings reveal an overlapping role for Syb1 and Syb2 (with Syb2 being dominant) in developing NMJs in mice. Moreover, because spontaneous release becomes Ca 2+-insensitive in Syb1lew/lew Syb2-/- NMJs, our findings suggest that synaptobrevin-based SNARE complexes play a critical role in conferring Ca 2+ sensitivity during spontaneous release.

Original languageEnglish (US)
Pages (from-to)6049-6066
Number of pages18
JournalJournal of Neuroscience
Volume39
Issue number31
DOIs
StatePublished - Jul 31 2019

Keywords

  • Evoked release
  • KO mice
  • Neuromuscular junction
  • Spontaneous release
  • Synapse formation
  • Synaptic transmission

ASJC Scopus subject areas

  • Neuroscience(all)

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