The synaptophysin/synaptobrevin interaction critically depends on the cholesterol content

J Neurochem. 2003 Jan;84(1):35-42. doi: 10.1046/j.1471-4159.2003.01258.x.


Synaptophysin interacts with synaptobrevin in membranes of adult small synaptic vesicles. The synaptophysin/synaptobrevin complex promotes synaptobrevin to built up functional SNARE complexes thereby modulating synaptic efficiency. Synaptophysin in addition is a cholesterol-binding protein. Depleting the membranous cholesterol content by filipin or beta-methylcyclodextrin (beta-MCD) decreased the solubility of synaptophysin in Triton X-100 with less effects on synaptobrevin. In small synaptic vesicles from rat brain the synaptophysin/synaptobrevin complex was diminished upon beta-MCD treatment as revealed by chemical cross-linking. Mice with a genetic mutation in the Niemann-Pick C1 gene developing a defect in cholesterol sorting showed significantly reduced amounts of the synaptophysin/synaptobrevin complex compared to their homo- or heterozygous littermates. Finally when using primary cultures of mouse hippocampus the synaptophysin/synaptobrevin complex was down-regulated after depleting the endogenous cholesterol content by the HMG-CoA-reductase inhibitor lovastatin. Alternatively, treatment with cholesterol up-regulated the synaptophysin/synaptobrevin interaction in these cultures. These data indicate that the synaptophysin/synaptobrevin interaction critically depends on a high cholesterol content in the membrane of synaptic vesicles. Variations in the availability of cholesterol may promote or impair synaptic efficiency by interfering with this complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticholesteremic Agents / pharmacology
  • Brain / metabolism
  • CHO Cells
  • Cholesterol / metabolism*
  • Cholesterol / pharmacology
  • Cricetinae
  • Cyclodextrins / pharmacology
  • Detergents
  • Filipin / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Lovastatin / pharmacology
  • Membrane Proteins / metabolism*
  • Membranes / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Niemann-Pick Diseases / genetics
  • Niemann-Pick Diseases / metabolism
  • Octoxynol
  • Protein Transport
  • R-SNARE Proteins
  • Rats
  • Solubility
  • Synaptic Vesicles / metabolism
  • Synaptophysin / chemistry
  • Synaptophysin / metabolism*
  • Up-Regulation


  • Anticholesteremic Agents
  • Cyclodextrins
  • Detergents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Membrane Proteins
  • R-SNARE Proteins
  • Synaptophysin
  • Filipin
  • Octoxynol
  • Cholesterol
  • Lovastatin