The synaptophysin/synaptobrevin interaction critically depends on the cholesterol content

Diana Mitter, Clemens Reisinger, Britta Hinz, Susanne Hollmann, Sowmya V. Yelamanchili, Stephanie Treiber-Held, Thomas G. Ohm, Andreas Herrmann, Gudrun Ahnert-Hilger

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Abstract

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 β-methylcyclodextrin (β-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 β-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.

Original languageEnglish (US)
Pages (from-to)35-42
Number of pages8
JournalJournal of Neurochemistry
Volume84
Issue number1
DOIs
StatePublished - Jan 1 2003

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Keywords

  • Cholesterol
  • Small synaptic vesicles
  • Synapse maturation
  • Synaptobrevin
  • Synaptophysin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Mitter, D., Reisinger, C., Hinz, B., Hollmann, S., Yelamanchili, S. V., Treiber-Held, S., Ohm, T. G., Herrmann, A., & Ahnert-Hilger, G. (2003). The synaptophysin/synaptobrevin interaction critically depends on the cholesterol content. Journal of Neurochemistry, 84(1), 35-42. https://doi.org/10.1046/j.1471-4159.2003.01258.x