The synaptophysin/synaptobrevin interaction critically depends on the cholesterol content

• Published in: Journal of neurochemistry Vol. 84; no. 1; pp. 35 - 42
• Main Authors: Mitter, Diana, Reisinger, Clemens, Hinz, Britta, Hollmann, Susanne, Yelamanchili, Sowmya V., Treiber‐Held, Stephanie, Ohm, Thomas G., Herrmann, Andreas, Ahnert‐Hilger, Gudrun
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.01.2003; Blackwell
• Subjects: Animals; Anticholesteremic Agents - pharmacology; Biological and medical sciences; Brain - metabolism; Cell physiology; CHO Cells; cholesterol; Cholesterol - metabolism; Cholesterol - pharmacology; Cricetinae; Cyclodextrins - pharmacology; Detergents; Filipin - pharmacology; Fundamental and applied biological sciences. Psychology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Lovastatin - pharmacology; Membrane Proteins - metabolism; Membranes - metabolism; Mice; Mice, Inbred BALB C; Molecular and cellular biology; Neurotransmission; Niemann-Pick Diseases - genetics; Niemann-Pick Diseases - metabolism; Octoxynol; Protein Transport; R-SNARE Proteins; Rats; small synaptic vesicles; Solubility; synapse maturation; Synaptic Vesicles - metabolism; synaptobrevin; synaptophysin; Synaptophysin - chemistry; Synaptophysin - metabolism; Up-Regulation; Synaptophysin; SNARE protein; Rat; Synaptic membrane; small synaptic vesicles; Rodentia; Synaptic vesicle; Lipids; Molecular interaction; In vitro; Cholesterol; Synaptobrevin; Filipin; Binding protein; synapse maturation; Vertebrata; Mammalia; Mouse; Niemann Pick disease; Mutation; Neurotransmission
• ISSN: 0022-3042; 1471-4159
• 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 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.