RT Journal
A1 Long, A. Ashleigh
A1 Kim, Eunju
A1 Leung, Hung-Tat
A1 Woodruff, Elvin
A1 An, Lingling
A1 Doerge, R. W.
A1 Pak, William L.
A1 Broadie, Kendal
T1 Presynaptic Calcium Channel Localization and Calcium-Dependent Synaptic Vesicle Exocytosis Regulated by the Fuseless Protein
JF The Journal of Neuroscience 
JO The Journal of Neuroscience 
YR 2008 
FD April 02 
VO 28 
IS 14 
SP 3668 
OP 3682 
DO 10.1523/JNEUROSCI.5553-07.2008 
UL http://www.jneurosci.org/content/28/14/3668.abstract 
AB A systematic forward genetic Drosophila screen for electroretinogram mutants lacking synaptic transients identified the fuseless (fusl) gene, which encodes a predicted eight-pass transmembrane protein in the presynaptic membrane. Null fusl mutants display >75% reduction in evoked synaptic transmission but, conversely, an approximately threefold increase in the frequency and amplitude of spontaneous synaptic vesicle fusion events. These neurotransmission defects are rescued by a wild-type fusl transgene targeted only to the presynaptic cell, demonstrating a strictly presynaptic requirement for Fusl function. Defects in FM dye turnover at the synapse show a severely impaired exo-endo synaptic vesicle cycling pool. Consistently, ultrastructural analyses reveal accumulated vesicles arrested in clustered and docked pools at presynaptic active zones. In the absence of Fusl, calcium-dependent neurotransmitter release is dramatically compromised and there is little enhancement of synaptic efficacy with elevated external Ca2+ concentrations. These defects are causally linked with severe loss of the Cacophony voltage-gated Ca2+ channels, which fail to localize normally at presynaptic active zone domains in the absence of Fusl. These data indicate that Fusl regulates assembly of the presynaptic active zone Ca2+ channel domains required for efficient coupling of the Ca2+ influx and synaptic vesicle exocytosis during neurotransmission.