Equivalent effects of snake PLA2 neurotoxins and lysophospholipid-fatty acid mixtures.
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.
Rigoni
Michela
M
Department of Biomedical Sciences and Consiglio Nazionale Ricerche Institute of Neuroscience, University of Padova, Italy.
Caccin
Paola
P
Gschmeissner
Steve
S
Koster
Grielof
G
Postle
Anthony D
AD
Rossetto
Ornella
O
Schiavo
Giampietro
G
Montecucco
Cesare
C
D000818:Animals; D002478:Cells, Cultured; D004546:Elapid Venoms / Q000633:toxicity; D004951:Esterification; D005089:Exocytosis; D005227:Fatty Acids / Q000378:metabolism* / Q000633:toxicity; D018698:Glutamic Acid / Q000378:metabolism; D006868:Hydrolysis; D007700:Kinetics; D008051:Lipid Bilayers; D008246:Lysophospholipids / Q000378:metabolism* / Q000633:toxicity; D008297:Male; D013058:Mass Spectrometry; D008561:Membrane Fusion; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009498:Neurotoxins / Q000378:metabolism* / Q000633:toxicity; D018377:Neurotransmitter Agents / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism* / Q000633:toxicity; D054467:Phospholipases A2; D013569:Synapses / Q000187:drug effects / Q000648:ultrastructure; D013570:Synaptic Membranes / Q000378:metabolism / Q000502:physiology*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure
D004546:Elapid Venoms; D005227:Fatty Acids; D008051:Lipid Bilayers; D008246:Lysophospholipids; D008563:Membrane Lipids; D009498:Neurotoxins; D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D010741:Phospholipases A; D054467:Phospholipases A2