title: Complexin has opposite effects on two modes of synaptic vesicle fusion.
abstract: BACKGROUND
  Synaptic transmission can occur in a binary or graded fashion, depending on whether transmitter release is triggered by action potentials or by gradual changes in membrane potential. Molecular differences of these two types of fusion events and their differential regulation in a physiological context have yet to be addressed. Complexin is a conserved SNARE-binding protein that has been proposed to regulate both spontaneous and stimulus-evoked synaptic vesicle (SV) fusion.
  
  
  RESULTS
  Here we examine complexin function at a graded synapse in C. elegans. Null complexin (cpx-1) mutants are viable, although nervous system function is significantly impaired. Loss of CPX-1 results in a 3-fold increase in the rate of tonic synaptic transmission at the neuromuscular junction, whereas stimulus-evoked SV fusion is decreased 10-fold. A truncated CPX-1 missing its C-terminal domain can rescue stimulus-evoked synaptic vesicle exocytosis but fails to suppress tonic activity, demonstrating that these two modes of exocytosis can be distinguished at the molecular level. A CPX-1 variant with impaired SNARE binding also rescues evoked, but not tonic, neurotransmitter release. Finally, tonic, but not evoked, release can be rescued in a syntaxin point mutant by removing CPX-1. Rescue of either form of exocytosis partially restores locomotory behavior, indicating that both types of synaptic transmission are relevant.
  
  
  CONCLUSIONS
  These observations suggest a dual role for CPX-1: suppressing SV exocytosis, driven by low levels of endogenous neural activity, while promoting synchronous fusion of SVs driven by a depolarizing stimulus. Thus, patterns of synaptic activity regulate complexin's inhibitory and permissive roles at a graded synapse.
authors.affiliation: Department of Biochemistry, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.
authors.forename: Jesse A
authors.initials: JA
authors.lastname: Martin
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Hu
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Fenz
authors.forename: Joel
authors.initials: J
authors.lastname: Fernandez
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Dittman
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000166:cytology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D005071:Evoked Potentials / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000502:physiology*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D029742:Caenorhabditis elegans Proteins; D009419:Nerve Tissue Proteins; C095992:complexin I