Ablation of All Synaptobrevin vSNAREs Blocks Evoked But Not Spontaneous Neurotransmitter Release at Neuromuscular Synapses
| Autor: | Yoshie Sugiura, Yun Liu, Thomas C. Südhof, Weichun Lin |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Synaptobrevin Neurogenesis Mutant Neuromuscular Junction Neurotransmission Synaptic Transmission Synaptic vesicle Neuromuscular junction R-SNARE Proteins Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Neurotransmitter Research Articles Mice Knockout Neurotransmitter Agents General Neuroscience Spontaneous synaptic transmission Embryo Mammalian Cell biology 030104 developmental biology medicine.anatomical_structure chemistry Synapses Synaptobrevin 2 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Neuroscience. 39:6049-6066 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.0403-19.2019 |
| Popis: | Synaptic transmission occurs when an action potential triggers neurotransmitter release via the fusion of synaptic vesicles with the pre-synaptic 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 pre-synaptic 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 ( Syb1 lew/lew ) or synaptobrevin 2 ( Syb2 —/— ), and those lacking both ( Syb1 lew/lew Syb2 —/— ). We found that compared with controls: (1) the number and size of NMJs was markedly increased in Syb2 —/— and Syb1 lew/lew Syb2 —/— mice, but not in Syb1 lew/lew mice; (2) synaptic vesicle density was markedly reduced in Syb1 lew/lew Syb2 —/— NMJs, and (3) evoked neurotransmission was markedly reduced in Syb2 —/— NMJs and completely abolished in Syb1 lew/lew Syb2 —/— NMJs. Surprisingly, however, spontaneous neurotransmission persists in the absence of both Syb1 and Syb2. Furthermore, spontaneous neurotransmission remains constant in Syb1 lew/lew Syb2 —/— 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 Syb1 lew/lew Syb2 —/— NMJs, our findings suggest that synaptobrevin-based SNARE complexes play a critical role in conferring Ca 2+ sensitivity during spontaneous release. SIGNIFICANCE STATEMENT Neurotransmitters can be released at synapses with (evoked) or without (spontaneous) the influence of action potentials. Whereas evoked neurotransmission requires Ca 2+ influx, those underlying the spontaneous neurotransmission may occur with or without Ca 2+ . Our findings show that, in the absence neuronal vSNARE synaptobrevin-1 and synaptobrevin-2, evoked neurotransmission is completely abolished; however, spontaneous synaptic transmission not only persists but even increased. Furthermore, spontaneous synaptic transmission that is normally highly Ca 2+ -sensitive became Ca 2+ -independent upon deletion of vSNARE synaptobrevin-1 and synaptobrevin-2. These findings reveal distinct mechanisms for evoked and spontaneous neurotransmitter release. Moreover, these findings suggest that synaptobrevin-based SNARE complexes play critical roles in conferring Ca 2+ sensitivity during spontaneous neurotransmission at developing neuromuscular synapses in mice. |
| Databáze: | OpenAIRE |
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