Calpains participate in nerve terminal degeneration induced by spider and snake presynaptic neurotoxins

a-latrotoxin and snake presynaptic phospholipases A2 neurotoxins target the presynaptic membrane of axon terminals of the neuromuscular junction causing paralysis. These neurotoxins display different biochemical activities, but similarly alter the presynaptic membrane permeability causing Ca2þ overload within the nerve terminals, which in turn induces nerve degeneration. Using different methods, here we show that the calciumactivated proteases calpains are involved in the cytoskeletal rearrangements that we have previously documented in neurons exposed to a-latrotoxin or to snake presynaptic phospholipases A2 neurotoxins. These results indicate that calpains, activated by the massive calcium influx from the extracellular medium, target fundamental components of neuronal cytoskeleton such as spectrin and neurofilaments, whose cleavage is functional to the ensuing nerve terminal fragmentation.