Presynaptic calcium channel localization and calcium-dependent synaptic vesicle exocytosis regulated by the fuseless protein

A. Ashleigh Long, Eunju Kim, Hung Tat Leung, Elvin Woodruff, Lingling An, R. W. Doerge, William L. Pak, Kendal Broadie

Research output: Contribution to journalArticle

22 Scopus citations

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 languageEnglish (US)
Pages (from-to)3668-3682
Number of pages15
JournalJournal of Neuroscience
Volume28
Issue number14
DOIs
StatePublished - Apr 2 2008
Externally publishedYes

Keywords

  • Drosophila
  • Exocytosis
  • Neuromuscular junction
  • Photoreceptor
  • Synapse
  • Synaptic vesicle

ASJC Scopus subject areas

  • Neuroscience(all)

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