ROLE OF SYNAPTOTAGMIN 7 IN REGULATING PRESYNAPTIC FUNCTION AT THE <EM>DROSOPHILA</EM> NEUROMUSCULAR JUNCTION

Calcium signals contribute to several fundamental presynaptic functions, such as synaptic vesicle (SV) release, recycling, replenishment of the readily releasable pool (RRP) and synaptic plasticity. One way to coordinate these processes is to utilize calcium sensing proteins with different demands to the kinetics and amplitudes of the calcium signals like the family of synaptotagmin proteins. In mammalian synapses fast and low affinity synaptotagmins are known to ensure synchronous SV release, while the slower but higher affinity synaptotagmin 7 (Syt7) contributes to the regulation of short-term plasticity, RRP replenishment and asynchronous release (AR). Although it has been suggested that many of the mammalian Syt7 functions may not be conserved in flies (Guan et al., 2020), we find that Syt7 regulates SV replenishment and AR together with the voltage gated calcium channel (VGCC) DmCa1D (homolog to vertebrate Ca_v1) at the NMJ. First, Syt7 is required for the fast phase of readily releasable pool (RRP) recovery after high frequency stimulation induced depletion. Ca_v1 and the plasma membrane bound calcium ATPase (PMCA) alter this function possibly by regulating calcium influx into the active zone (Krick et al., PNAS, 2021). Second, Syt7 is required for AR. At the NMJ, AR is unmasked in basigin mutants, depends on calcium influx through Ca_v1 and is abolished by concomitant Syt7 knock out. Syt7 induced AR increases total charge transfer during high frequency activity, as also reported in mammals. Our data suggest that Syt7 contributes to the cooperative tuning and orchestration of RRP replenishment, and AR, as in mammals.