Drosophila Hsc70-4 is critical for neurotransmitter exocytosis in vivo

Previous in vitro studies of cysteine-string protein (CSP) imply a potentia l role for the clathrin-uncoating ATPase Hsc70 in exocytosis. We show that hypomorphic mutations in Drosophila Hsc70-4 (Hsc4) impair nerve-evoked neur otransmitter release, but not synaptic vesicle recycling in vivo. The loss of release can be restored by increasing external or internal Ca2+ and is c aused by a reduced Ca2+ sensitivity of exocytosis downstream of Ca2+ entry. Hsc4 and CSP are likely to act in common pathways, as indicated by their i n vitro protein interaction, the similar loss of evoked release in individu al and double mutants, and genetic interactions causing a loss of release i n trans-heterozygous hsc4-csp double mutants. We suggest that Hsc4 and CSP cooperatively augment the probability of release by increasing the Ca2+ sen sitivity of vesicle fusion.