The UNC-13 protein family has been suggested to be critical for synaptic
vesicle dynamics based on its interactions with Syntaxin, Munc-18 and Doc
2. We cloned the Drosophila homolog (Dunc-13) and characterized
its function using a combination of electrophysiology and ultrastructural
analyses. Dunc-13 contained a C1 lipid-binding motif and two C2 calcium-binding
domains, and its expression was restricted to neurons. Elimination of
dunc-13 expression abolished synaptic transmission, an effect comparable
only to removal of the core complex proteins Syntaxin and Synaptobrevin. Transmitter
release remained impaired under elevated calcium influx or application of
hyperosmotic saline. Ultrastructurally, mutant terminals accumulated docked
vesicles at presynaptic release sites. We conclude that Dunc-13 is essential
for a stage of neurotransmission following vesicle docking and before fusion.
. We cloned the Drosophila homolog (Dunc-13) and characterized
its function using a combination of electrophysiology and ultrastructural
analyses. Dunc-13 contained a C1 lipid-binding motif and two C2 calcium-binding
domains, and its expression was restricted to neurons. Elimination of
dunc-13 expression abolished synaptic transmission, an effect comparable
only to removal of the core complex proteins Syntaxin and Synaptobrevin. Transmitter
release remained impaired under elevated calcium influx or application of
hyperosmotic saline. Ultrastructurally, mutant terminals accumulated docked
vesicles at presynaptic release sites. We conclude that Dunc-13 is essential
for a stage of neurotransmission following vesicle docking and before fusion.
