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Science 310 (5754): 1678-1680

Copyright © 2005 by the American Association for the Advancement of Science

Equivalent Effects of Snake PLA2 Neurotoxins and Lysophospholipid-Fatty Acid Mixtures

Michela Rigoni,1 Paola Caccin,1 Steve Gschmeissner,2 Grielof Koster,3 Anthony D. Postle,3 Ornella Rossetto,1 Giampietro Schiavo,2 Cesare Montecucco1*

Abstract: Snake presynaptic phospholipase A2 neurotoxins (SPANs) paralyze the neuromuscular junction (NMJ). Upon intoxication, the NMJ enlarges and has a reduced content of synaptic vesicles, and primary neuronal cultures show synaptic swelling with surface exposure of the lumenal domain of the synaptic vesicle protein synaptotagmin I. Concomitantly, these neurotoxins induce exocytosis of neurotransmitters. We found that an equimolar mixture of lysophospholipids and fatty acids closely mimics all of the biological effects of SPANs. These results draw attention to the possible role of local lipid changes in synaptic vesicle release and provide new tools for the study of exocytosis.

1 Department of Biomedical Sciences and Consiglio Nazionale Ricerche Institute of Neuroscience, University of Padova, Italy.
2 Cancer Research UK, London Research Institute, London, UK.
3 School of Medicine, University of Southampton, UK.

* To whom correspondence should be addressed. E-mail: cesare.montecucco{at}unipd.it


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