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Neurotoxic phospholipases directly affect synaptic vesicle function
Author(s) -
Treppmann Philipp,
Brunk Irene,
Afube Terence,
Richter Karin,
AhnertHilger Gudrun
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07247.x
Subject(s) - synaptic vesicle , synaptobrevin , neurotransmission , exocytosis , synaptophysin , biology , microbiology and biotechnology , synaptic vesicle recycling , neurotransmitter , synapsin , biophysics , biochemistry , vesicle , secretion , receptor , immunohistochemistry , membrane , immunology
J. Neurochem. (2011) 117 , 757–764. Abstract Snake neurotoxic phospholipases (SPAN) exclusively affect pre‐synaptic nerve terminals where they lead to a block of neurotransmission by not fully understood mechanisms. Here, we report that the SPANs, taipoxin and paradoxin, in nanomolar concentrations directly dissociate the synaptophysin/synaptobrevin (Syp/Syb) complex on isolated synaptic vesicles in the presence of synaptosomal cytosol. The phospholipase activity of SPANs depends on Ca 2+ but the dissociation of the Syp/Syb complex does not require Ca 2+ . Ca 2+ (100 μM free) alone also dissociates the Syp/Syb complex in the presence of cytosol. Treatment with SPANs disturbs the lipid raft association of synaptophysin and synaptobrevin comparable to cholesterol depletion by β‐methyl‐cyclodextrin while Ca 2+ alone has no effect. SPANs but not Ca 2+ directly inhibit vesicular uptake of serotonin and glutamate. It is concluded that SPANs directly affect vesicular properties independent from their Ca 2+ ‐dependent phospholipase activity. SPANs and Ca 2+ dissociate the Syp/Syb complex as a prerequisite for exocytosis. SPANs also prevent the filling of synaptic vesicles thereby adding to the inhibition of neurotransmission.