Snake PLA2 neurotoxins

Fig. 5 The snake PLA2 neurotoxin is depicted here as a snake, which binds to an active zone, i.e., a synaptic vesicle (SV) release site, and hydrolyses the phospholipids of the external layer of the presynaptic membrane (green) with formation of the inverted-cone shaped lysophospholipid (yellow) and the cone-shaped fatty acid (dark blue). Fatty acids rapidly equilibrate by trans-bilayer movement among the two layers of the presynaptic membrane. In such a way lysophospholipids, which induce a positive curvature of the membrane, are present in trans and fatty acid, which induce a negative curvature, are present also in cis, with respect to the fusion site. This membrane conformation facilitates the transition from a hemifusion intermediate to a pore. Thus, the action of the toxin promotes exocytosis of neurotransmitter (NT) (from the left to the right panel) and, for the same membrane topological reason, it inhibits the opposite process, i.e., the fission of the synaptic vesicle.

Rigoni M, Caccin P, Gschmeissner S, Koster G, Postle AD et al. (2005) Equivalent effects of snake pla2 neurotoxins and lysophospholipid-fatty acid mixtures. Science 310 1678-80 Rigoni M, Pizzo P, Schiavo G, Weston AE, Zatti G et al. (2007) Calcium influx and mitochondrial alterations at synapses exposed to snake neurotoxins or their phospholipid hydrolysis products. JBiolChem 282 11238-45... 

The Mode of Action of PLA2 Snake Presynaptic Neurotoxins. 146... 

The botulinum neurotoxins and the snake presynaptic PLA2 neurotoxins share three levels of interest (1) they are pathogenic to humans and animals, (2) they contribute to the understanding of the molecular steps of neurotransmission, and (3) their present and future clinical applications. In this chapter, these neurotoxins are considered in terms of mode of action and in relation to their potential use in cell biology and neuroscience research as well as therapeutics in some human neurodisorders. 

Presynaptic snake neurotoxins endowed with PLA2 activity (SPANs) are major components of the venom of four families of venomous snakes (Crotalidae, Elapidae, Hydrophiidae, and Viperidae). These neurotoxins play a crucial role in envenomation of the prey (Harris 1997) by causing a persistent blockade of neurotransmitter release from nerve terminals with a peripheral paralysis very similar to that of botulism (Connolly et al. 1995 Gutidrrez et al. 2006 Kularatne 2002 Prasampun et al. 2005 Theakston et al. 1990 Trevett et al. 1995 Warrell et al. 1983). 

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