<i>Drosophila</i> Synaptotagmin 7 negatively regulates synaptic vesicle release and replenishment in a dosage-dependent manner.

Abstract

Synchronous 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 <i>Drosophila Syt7</i> to 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. <i>Syt7</i> mutants also had a larger pool of readily-releasable vesicles, faster recovery following stimulation, and intact facilitation. <i>Syt1/Syt7</i> double mutants displayed more release than <i>Syt1</i> mutants 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 active zones. These findings indicate the two Ca²⁺ sensor model of SYT1 and SYT7 mediating all phases of neurotransmitter release and facilitation is not applicable at <i>Drosophila</i> synapses.