A high affinity acceptor for phospholipase A2 with neurotoxic activity is a calmodulin

Area of Science:

• Neuroscience
• Biochemistry
• Toxicology

Background:

• Snake venom phospholipase A(2) (PLA(2)) are neurotoxic proteins.
• Ammodytoxin C is a potent presynaptic neurotoxin.
• The cellular targets of these toxins are not fully understood.

Purpose of the Study:

• To identify and characterize high-affinity binding proteins for ammodytoxin C.
• To investigate the role of these binding proteins in PLA(2) neurotoxicity.

Main Methods:

• Purification of the toxin-binding protein from porcine cerebral cortex using affinity chromatography.
• Characterization of the binding protein using specific inhibitors and mass spectrometry.
• Analysis of binding specificity with various PLA(2) enzymes and toxins.

Main Results:

• A high-affinity binding protein for ammodytoxin C was purified.
• The binding protein was identified as calmodulin via tandem mass spectrometry.
• Binding was specific to neurotoxic PLA(2) and related toxins, but not non-toxic PLA(2).

Conclusions:

• Calmodulin is a high-affinity binding protein for ammodytoxin C.
• The interaction suggests that secretory PLA(2) neurotoxins require internalization to exert toxicity.
• Calmodulin may play a role in the Ca(2+)-regulated process of synaptic transmission blockade by ammodytoxin.