Drosophila Synaptotagmin 7 negatively regulates synaptic vesicle fusion and replenishment in a dosage-dependent manner

Abstract

AbstractSynchronous neurotransmitter release is triggered by Ca2+binding to the synaptic vesicle protein Synaptotagmin 1, while asynchronous fusion and short-term facilitation is hypothesized to be mediated by plasma membrane-localized Synaptotagmin 7 (SYT7). We generated mutations in DrosophilaSyt7to determine if it plays a conserved role as the Ca2+sensor for these processes. Electrophysiology and quantal imaging revealed evoked release was elevated 2-fold.Syt7mutants also had a larger pool of readily-releasable vesicles, faster recovery following stimulation, and robust facilitation.Syt1/Syt7double mutants displayed more release thanSyt1mutants alone, indicating SYT7 does not mediate the residual asynchronous release remaining in the absence of SYT1. SYT7 localizes to an internal membrane tubular network within the peri-active zone, but does not enrich at release sites. These findings indicate the two Ca2+sensor model of SYT1 and SYT7 mediating all phases of neurotransmitter release and facilitation is not applicable at Drosophila synapses.