論文 - 詳細
| RRC ID | 59370 |
|---|---|
| 著者 | Li L, Liu H, Wang W, Chandra M, Collins BM, Hu Z. |
| タイトル | SNT-1 Functions as the Ca2+ Sensor for Tonic and Evoked Neurotransmitter Release in Caenorhabditis Elegans. |
| ジャーナル | J Neurosci |
| Abstract |
Synaptotagmin-1 (Syt1) binds Ca2+ through its tandem C2 domains (C2A and C2B) and triggers Ca2+-dependent neurotransmitter release. Here, we show that snt-1, the homolog of mammalian Syt1, functions as the Ca2+ sensor for both tonic and evoked neurotransmitter release at the Caenorhabditis elegans neuromuscular junction. Mutations that disrupt Ca2+ binding in double C2 domains of SNT-1 significantly impaired tonic release, whereas disrupting Ca2+ binding in a single C2 domain had no effect, indicating that the Ca2+ binding of the two C2 domains is functionally redundant for tonic release. Stimulus-evoked release was significantly reduced in snt-1 mutants, with prolonged release latency as well as faster rise and decay kinetics. Unlike tonic release, evoked release was triggered by Ca2+ binding solely to the C2B domain. Moreover, we showed that SNT-1 plays an essential role in the priming process in different subpopulations of synaptic vesicles with tight or loose coupling to Ca2+ entry.SIGNIFICANCE STATEMENT We showed that SNT-1 in Caenorhabditis elegans regulates evoked neurotransmitter release through Ca2+ binding to its C2B domain in a similar way to Syt1 in the mouse CNS and the fly neuromuscular junction. However, the largely decreased tonic release in snt-1 mutants argues SNT-1 has a clamping function. Indeed, Ca2+-binding mutations in the C2 domains in SNT-1 significantly reduced the frequency of the miniature EPSC, indicating that SNT-1 also acts as a Ca2+ sensor for tonic release. Therefore, revealing the differential mechanisms between invertebrates and vertebrates will provide significant insights into our understanding how synaptic vesicle fusion is regulated. |
| 巻・号 | 38(23) |
| ページ | 5313-5324 |
| 公開日 | 2018-6-6 |
| DOI | 10.1523/JNEUROSCI.3097-17.2018 |
| PII | JNEUROSCI.3097-17.2018 |
| PMID | 29760174 |
| PMC | PMC6596004 |
| MeSH | Animals Caenorhabditis elegans Calcium Signaling / physiology* Excitatory Postsynaptic Potentials / physiology Neuromuscular Junction / metabolism Neurotransmitter Agents / metabolism* Protein Domains Synaptic Transmission / physiology* Synaptic Vesicles / metabolism* Synaptotagmin I / metabolism* |
| IF | 6.074 |
| 引用数 | 0 |
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
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