The aqueous extract of the venom glands of black widow spiders was fractionated on a column of Sephadex G-200 and then on a column of DEAE-Sephadex A-50 pH 8.2. A protein fraction was obtained that caused a great increase in the frequency of occurrence of miniature end plate potentials at the frog neuromuscular junction, and caused swelling of the nerve terminals and depleted them of their vesi...

Presynaptic nerve terminals contain between several hundred vesicles (for example in small CNS synapses) and several tens of thousands (as in neuromuscular junctions). Although it has long been assumed that such high numbers of vesicles are required to sustain neurotransmission during conditions of high demand, we found that activity in vivo requires the recycling of only a few percent of the v...

Curarized cutaneous pectoris nerve-muscle preparations from frogs were stimulated at 10/s or at 2/s for periods ranging from 20 min to 4 h. End plate potential were recorded intracellularly and used to estimate the quantity of transmitter secreted during the period of stimulation. At the ends of the periods of stimulation the preparations were either fixed for electron microscopy or treated wit...

alpha-Latrotoxin, a potent neurotoxin from black widow spider venom, triggers synaptic vesicle exocytosis from presynaptic nerve terminals. alpha-Latrotoxin is a large protein toxin (120 kDa) that contains 22 ankyrin repeats. In stimulating exocytosis, alpha-latrotoxin binds to two distinct families of neuronal cell-surface receptors, neurexins and CLs (Cirl/latrophilins), which probably have a...

alpha-latrotoxin (LTX), a 120 kDa protein in black widow spider venom, triggers massive neurotransmitter exocytosis. Previous studies have highlighted a role for both intrinsic pore-forming activity and receptor binding in the action of this toxin. Intriguingly, activation of a presynaptic G protein-coupled receptor, latrophilin, may trigger release independent of pore-formation. Here we have u...

Gene duplication and positive selection can be important determinants of the evolution of venom, a protein-rich secretion used in prey capture and defense. In a typical model of venom evolution, gene duplicates switch to venom gland expression and change function under the action of positive selection, which together with further duplication produces large gene families encoding diverse toxins....

alpha-Latrotoxin from the venom of black widow spider induces and augments neurotransmitter and hormone release by way of extracellular Ca(2+) influx and cellular signal transduction pathways. By using whole cell current and capacitance recording, the photolysis of caged Ca(2+), and Ca(2+) microfluorometry and amperometry, we investigated the stimulating effect and mechanism of alpha-latrotoxin...

The botulinum neurotoxins (BoNTs) exhibit zinc-dependent proteolytic activity against members of the core synaptic membrane fusion complex, preventing neurotransmitter release and resulting in neuromuscular paralysis. No pharmacologic therapies have been identified that clinically relieve botulinum poisoning. The black widow spider venom α-latrotoxin (LTX) has the potential to attenuate the sev...