PT - JOURNAL ARTICLE AU - Lei Li AU - Haowen Liu AU - Wei Wang AU - Mintu Chandra AU - Brett M. Collins AU - Zhitao Hu TI - SNT-1 Functions as the Ca<sup>2+</sup> Sensor for Tonic and Evoked Neurotransmitter Release in <em>Caenorhabditis Elegans</em> AID - 10.1523/JNEUROSCI.3097-17.2018 DP - 2018 Jun 06 TA - The Journal of Neuroscience PG - 5313--5324 VI - 38 IP - 23 4099 - http://www.jneurosci.org/content/38/23/5313.short 4100 - http://www.jneurosci.org/content/38/23/5313.full SO - J. Neurosci.2018 Jun 06; 38 AB - 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.