Drosophila synaptotagmin I null mutants show severe alterations in vesicle populations but calcium-binding motif mutants do not (original) (raw)
2006, The Journal of Comparative Neurology
Synaptotagmin I is a synaptic vesicle protein postulated to mediate vesicle docking, vesicle recycling, and the Ca 2ϩ sensing required to trigger vesicle fusion. Analysis of synaptotagmin I knockouts (sytI NULL mutants) in both Drosophila and mice led to these hypotheses. Although much research on the mechanisms of synaptic transmission in Drosophila is performed at the third instar neuromuscular junction, the ultrastructure of this synapse has never been analyzed in sytI NULL mutants. Here we report severe synaptic vesicle depletion, an accumulation of large vesicles, and decreased vesicle docking at sytI NULL third instar neuromuscular junctions. Mutations in synaptotagmin I's C 2 B Ca 2ϩ -binding motif nearly abolish synaptic transmission and decrease the apparent Ca 2ϩ affinity of neurotransmitter release. Although this result is consistent with disruption of the Ca 2ϩ sensor, synaptic vesicle depletion and/or redistribution away from the site of Ca 2ϩ influx could produce a similar phenotype. To address this question, we examined vesicle distributions at neuromuscular junctions from third instar C 2 B Ca 2ϩ -binding motif mutants and transgenic wild-type controls. The number of docked vesicles and the overall number of synaptic vesicles in the vicinity of active zones was unchanged in the mutants. We conclude that the near elimination of synaptic transmission and the decrease in the Ca 2ϩ affinity of release observed in C 2 B Ca 2ϩ -binding motif mutants is not due to altered synaptic vesicle distribution but rather is a direct result of disrupting synaptotagmin I's ability to bind Ca 2ϩ . Thus, Ca 2ϩ binding by the C 2 B domain mediates a postdocking step in fusion.
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