SNT-1 functions as the Ca2+ sensor for tonic and evoked neurotransmitter release in caenorhabditis elegans

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.