R. Renden et al., Drosophila CAPS is an essential gene that regulates dense-core vesicle release and synaptic vesicle fusion, NEURON, 31(3), 2001, pp. 421-437
Calcium-activated protein for secretion (CAPS) is proposed to play an essen
tial role in Ca2+-regulated dense-core vesicle exocytosis in vertebrate neu
roendocrine cells. Here we report the cloning, mutation, and characterizati
on of the Drosophila ortholog (dCAPS). Null dCAPS mutants display locomotor
y deficits and complete embryonic lethality. The mutant NMJ reveals a 50% l
oss in evoked glutamatergic transmission, and an accumulation of synaptic v
esicles at active zones. Importantly, dCAPS mutants display a highly specif
ic 3-fold accumulation of dense-core vesicles in synaptic terminals, which
was not observed in mutants that completely arrest synaptic vesicle exocyto
sis. Targeted transgenic CAPS expression in identified motoneurons fails to
rescue dCAPS neurotransmission defects, demonstrating a cell nonautonomous
role in synaptic vesicle fusion. We conclude that dCAPS is required for de
nse-core vesicle release and that a dCAPS-dependent mechanism modulates syn
aptic vesicle release at glutamatergic synapses.