Drosophila Hsc70-4 is critical for neurotransmitter exocytosis in vivo.
Previous in vitro studies of cysteine-string protein (CSP) imply a potential role for the clathrin-uncoating ATPase Hsc70 in exocytosis. We show that hypomorphic mutations in Drosophila Hsc70-4 (Hsc4) impair nerve-evoked neurotransmitter release, but not synaptic vesicle recycling in vivo. The loss of release can be restored by increasing external or internal Ca(2+) and is caused by a reduced Ca(2+) sensitivity of exocytosis downstream of Ca(2+) entry. Hsc4 and CSP are likely to act in common pathways, as indicated by their in vitro protein interaction, the similar loss of evoked release in individual and double mutants, and genetic interactions causing a loss of release in trans-heterozygous hsc4-csp double mutants. We suggest that Hsc4 and CSP cooperatively augment the probability of release by increasing the Ca(2+) sensitivity of vesicle fusion.
Bronk
P
P
Department of Neuroscience, 234d Stemmler Hall, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Wenniger
J J
JJ
Dawson-Scully
K
K
Guo
X
X
Hong
S
S
Atwood
H L
HL
Zinsmaier
K E
KE
D000005:Abdomen; D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D017931:DNA Primers; D004330:Drosophila / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins; D005089:Exocytosis / Q000502:physiology*; D050883:HSC70 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism*; D006579:Heterozygote; D007814:Larva; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000294:innervation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D018408:Patch-Clamp Techniques; D016133:Polymerase Chain Reaction; D013569:Synapses / Q000502:physiology
D017931:DNA Primers; D029721:Drosophila Proteins; D050883:HSC70 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C424447:Hsc70-4 protein, Drosophila; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; C088460:cysteine string protein; D002118:Calcium