Synaptotagmin is a synaptic vesicle protein implicated in neurotransmi
tter release. Molecular characterization of four mutant alleles of thi
s protein in Drosophila melanogaster has permitted an investigation of
synaptotagmin's role in synaptic physiology and of some of the struct
ural requirements for its function. Reduced levels of synaptotagmin re
sulted in a substantial alteration in synaptic function in the eye and
at larval neuromuscular junctions. Decreased neurotransmitter release
caused smaller evoked synaptic potentials. However, the frequency, bu
t not the size, of spontaneous quantal events was simultaneously incre
ased. These abnormalities do not appear to be secondary to a detectabl
e morphological change in the arborization of the synapse. The increas
ed frequency of spontaneous events was insufficient to deplete signifi
cantly the vesicle supply and thereby account for reduced transmission
. These data are discussed in the context of models in which synaptota
gmin's function includes a role in vesicle docking.