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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) paralyzethe neuromuscular junction (NMJ). Upon intoxication, the NMJenlarges and has a reduced content of synaptic vesicles, andprimary neuronal cultures show synaptic swelling with surfaceexposure of the lumenal domain of the synaptic vesicle proteinsynaptotagmin I. Concomitantly, these neurotoxins induce exocytosisof neurotransmitters. We found that an equimolar mixture oflysophospholipids and fatty acids closely mimics all of thebiological effects of SPANs. These results draw attention tothe possible role of local lipid changes in synaptic vesiclerelease 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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