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
リソース情報
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