The Neurotoxic Mode of Action of Venoms from the Spider Family Theraphosidae

Abstract

Spiders from the family Theraphosidae are typically generalist predators of both invertebrates and vertebrates. Due to their large size and popularity in the pet trade, obtaining large amounts of a diverse range of theraphosid venoms is easier than for any other spider family. This explains why ~25 % of all spider toxins described to date originate from theraphosids even though they account for only 2 % of the taxonomic diversity of spiders. The main components of theraphosid venoms are neurotoxic peptides (cysteine-rich mini-proteins) that act on ion channels in the central or peripheral nervous system in order to induce rapid paralysis and/or death of prey. Their venoms also contain toxins that inhibit proteolytic degradation and enzymes that aid in the spread of other venom components. Some compounds in theraphosid venoms cause pain in vertebrates, making them useful for predator deterrence. Most theraphosid venom peptides contain three disulfide bonds that form an inhibitor cystine knot motif, which endows these toxins with extreme chemical and thermal stability, as well as resistance to proteolytic degradation. These properties, as well as their high potency and selectivity for particular molecular targets, have made some theraphosid venom peptides valuable as pharmacological tools and as leads for therapeutics and bioinsecticides.