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First published on February 4, 2005; DOI: 10.1124/mol.104.005678

0026-895X/05/6706-1901-1908$20.00
Mol Pharmacol 67:1901-1908, 2005

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Taipoxin Induces Synaptic Vesicle Exocytosis and Disrupts the Interaction of Synaptophysin I with VAMP2

Dario Bonanomi, Maria Pennuto, Michela Rigoni, Ornella Rossetto, Cesare Montecucco, and Flavia Valtorta

Department of Neuroscience, S. Raffaele Scientific Institute and "Vita-Salute" University, Milan, Italy (D.B., M.P., F.V.); and Department of Biomedical Sciences, University of Padova, Italy (M.R., O.R., C.M.)

The application of the snake neurotoxin taipoxin to hippocampal neurons in culture induced Ca2+-dependent synaptic vesicle (SV) exocytosis, with swelling of nerve terminals and redistribution of SV proteins to the axolemma. Using digital imaging videomicroscopy to measure fluorescence resonance energy transfer in live neurons, we also found that taipoxin modulates the machinery for neurosecretion by causing dissociation of the SV proteins synaptobrevin 2 and synaptophysin I at a stage preceding taipoxin-induced facilitation of SV fusion. These early effects of the toxin are followed by severe impairment of SV exo-endocytosis, which might underlie the prevention of neurotransmitter release reported after intoxication by taipoxin.

Received July 30, 2004; accepted February 3, 2005

Address correspondence to: Flavia Valtorta, DIBIT 3A3, San Raffaele Scientific Institute, via Olgettina 58, 20132 Milan, Italy. E-mail: valtorta.flavia{at}hsr.it




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