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 Drosophila Syt7 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. Syt7 mutants also had a larger pool of readily-releasable vesicles, faster recovery following stimulation, and intact facilitation. Syt1/Syt7 double mutants displayed more release than Syt1 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 Drosophila synapses.
Highlights
Neurotransmitter release from presynaptic terminals is the primary mechanism of synaptic communication and is mediated by fusion of synaptic vesicles (SVs) with the plasma membrane at specific sites known as active zones (AZs) (Katz, 1969; Südhof, 2013; Zhai and Bellen, 2004).A highly conserved protein machinery composed of the SNARE complex drives fusion between the SV and AZ lipid bilayers (Littleton et al, 1998; Söllner et al, 1993; Sutton et al, 1998; Tucker et al, 2004)
The clustering of SYT1 homologs across evolution correlates with nervous system complexity, with the Trichoplax homolog forming the outlier member of the cluster
Short-term facilitation does not require Synaptotagmin 7 (SYT7). These results indicate SYT7 is a not a key asynchronous Ca2+ sensor in Drosophila, the protein has been implicated as the Ca2+ sensor for facilitation (Chen et al, 2017; Jackman et al, 2016; Turecek and Regehr, 2018), a short-term form of presynaptic plasticity that results in enhanced SV fusion during closely-spaced stimuli
Summary
Neurotransmitter release from presynaptic terminals is the primary mechanism of synaptic communication and is mediated by fusion of synaptic vesicles (SVs) with the plasma membrane at specific sites known as active zones (AZs) (Katz, 1969; Südhof, 2013; Zhai and Bellen, 2004).A highly conserved protein machinery composed of the SNARE complex drives fusion between the SV and AZ lipid bilayers (Littleton et al, 1998; Söllner et al, 1993; Sutton et al, 1998; Tucker et al, 2004). The majority of SVs fuse during a synchronous phase that occurs within a few milliseconds of Ca2+ entry (Borst and Sakmann, 1996; Goda and Stevens, 1994; Llinás et al, 1981; Sabatini and Regehr, 1996; Yoshihara and Littleton, 2002). Asynchronous release normally accounts for less than 5% of SV fusion following single action potentials at Drosophila neuromuscular junctions (NMJs) (Jorquera et al, 2012). This slower phase of release becomes more prominent during high rates of stimulation (Atluri and Regehr, 1998; Lu and Trussell, 2000; Rozov et al, 2019; Zucker and Regehr, 2002)
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