Synaptic Membranes Bend to the Will of a Neurotoxin

摘要

Discovery in neurobiology is replete with examples of scientists using toxins that bind, neutralize, or cleave physiologically important cellular proteins. The inhibitory binding of saxitoxin and tetrodotoxin to the sodium channel, conotoxin and spi- der toxins to the calcium channel, α-bungarotoxin to the acetylcholine receptor, and clostridial toxins to SNARE proteins that facilitate high-fidelity membrane fusion—these toxins were not only instrumental in their respective isolation and investigation but enabled the dissection of basic cellular and physiological mechanisms. On page 1678 in this issue, Rigoni et al. report how the action of phospholi-pase A2, a neurotoxic component of snake venom that paralyzes the neuromuscular junction, reveals a new regulatory mechanism for neurotransmitter release at the synapse. Lysophospholipids and free fatty acids, the hydrolytic products of this lipase, alter the energetics of the presynaptic membrane, thus affecting its disposition to bend and fuse with synaptic vesicles.