Abstract
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 Ca 2+ channel domains required for efficient coupling of the Ca 2+ influx and synaptic vesicle exocytosis during neurotransmission.
Original language | English (US) |
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Pages (from-to) | 3668-3682 |
Number of pages | 15 |
Journal | Journal of Neuroscience |
Volume | 28 |
Issue number | 14 |
DOIs | |
State | Published - Apr 2 2008 |
Externally published | Yes |
Keywords
- Drosophila
- Exocytosis
- Neuromuscular junction
- Photoreceptor
- Synapse
- Synaptic vesicle
ASJC Scopus subject areas
- General Neuroscience