Regulation of the cytoskeleton is fundamental to the development and functioning of
synaptic terminals, such as neuromuscular junctions. Nevertheless, despite identification
of numerous proteins that regulate synaptic actin and microtubule dynamics, the mechanisms
of cytoskeletal control during terminal arbor formation has remained largely elusive.
Here, we show that DAAM, a member of the formin family of cytoskeleton organizing
factors, is an important presynaptic regulator of neuromuscular junction development
in Drosophila We demonstrate that the actin filament assembly activity of DAAM plays
a negligible role in terminal formation; rather, DAAM is necessary for synaptic microtubule
organization. Genetic interaction studies consistently link DAAM with the Wg/Ank2/Futsch
module of microtubule regulation and bouton formation. Finally, we provide evidence
that DAAM is tightly associated with the synaptic active zone scaffold, and electrophysiological
data point to a role in the modulation of synaptic vesicle release. Based on these
results, we propose that DAAM is an important cytoskeletal effector element of the
Wg/Ank2 pathway involved in the determination of basic synaptic structures, and, additionally,
DAAM may couple the active zone scaffold to the presynaptic cytoskeleton.
