TY - JOUR
T1 - Ablation of all synaptobrevin vSNAREs blocks evoked but not spontaneous neurotransmitter release at neuromuscular synapses
AU - Liu, Yun
AU - Sugiura, Yoshie
AU - Südhof, Thomas C.
AU - Lin, Weichun
N1 - Publisher Copyright:
Copyright © 2019 the authors.
PY - 2019/7/31
Y1 - 2019/7/31
N2 - 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.
AB - 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.
KW - Evoked release
KW - KO mice
KW - Neuromuscular junction
KW - Spontaneous release
KW - Synapse formation
KW - Synaptic transmission
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U2 - 10.1523/JNEUROSCI.0403-19.2019
DO - 10.1523/JNEUROSCI.0403-19.2019
M3 - Article
C2 - 31160536
AN - SCOPUS:85070852578
SN - 0270-6474
VL - 39
SP - 6049
EP - 6066
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 31
ER -