How do presynaptic PLA2 neurotoxins block nerve terminals?
Snake presynaptic neurotoxins with phospholipase A2 activity block nerve terminals in an unknown way. Here, we propose that they enter the lumen of synaptic vesicles following endocytosis and hydrolyse phospholipids of the inner leaflet of the membrane. The transmembrane pH gradient drives the translocation of fatty acids to the cytosolic monolayer, leaving lysophospholipids on the lumenal layer. Such vesicles are highly fusogenic and release neurotransmitter upon fusion with the presynaptic membrane, but cannot be retrieved because of the high local concentration of fatty acids and lysophospholipids, which prevents vesicle neck closure.
Montecucco
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C
Centro CNR Biomembrane and Dipartimento di Scienze Biomediche, Università di Padova, Via G. Colombo 3, 35121 Padova, Italy. cesare@civ.bio.unipd.it
Rossetto
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O
D004546:Elapid Venoms / Q000633:toxicity; D008954:Models, Biological; D009411:Nerve Endings / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D018377:Neurotransmitter Agents / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D012910:Snake Venoms / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D013997:Time Factors
D004546:Elapid Venoms; D009498:Neurotoxins; D018377:Neurotransmitter Agents; D012910:Snake Venoms; C015523:taipoxin; D010741:Phospholipases A; D054467:Phospholipases A2