Exploiting animal toxins to probe molecular mechanisms of pain
- Author(s): Zhang, Chuchu
- Advisor(s): Julius, David
- Basbaum, Allan I
- et al.
Venoms from spiders, snakes, cone snails and scorpions have evolved to produce a
vast pharmacopoeia of toxins that modulate receptor or channel function as a means of
producing shock, hemolysis, paralysis and pain. As such, venoms from these animals
represent a rich potential source of potent and selective toxins that can be exploited to
study and manipulate somatosensory and nociceptive signaling pathways. In this work, I
have identified and characterized two novel toxins from the Brazilian lancehead pit viper
(Bothrops moojeni) and Tanzania blue ringleg centipede (Scolopendra morsitans). The
Brazilian lancehead snake venom contains a novel secreted phospholipase A2
(sPLA2)-like protein that can promote ATP release from pannexin hemichannels.
Studies on the cellular and behavioral effects of this toxin reveal a role of regulated
endogenous nucleotide release in nociception. The discovered Tanzania blue ringleg
centipede toxin represents a new family of toxins that show evolutionary relationship
with α-scorpion toxins and could potentially function as potassium channel blockers.