delta-Conotoxin SuVIA suggests an evolutionary link between ancestral predator defence and the origin of fish-hunting behaviour in carnivorous cone snails

摘要

Some venomous cone snails feed on small fishes using an immobilizing combination of synergistic venom peptides that target K-v and Na-v channels. As part of this envenomation strategy, delta-conotoxins are potent ichtyotoxins that enhance Na-v channel function. delta-Conotoxins belong to an ancient and widely distributed gene superfamily, but any evolutionary link from ancestral worm-eating cone snails to modern piscivorous species has not been elucidated. Here, we report the discovery of SuVIA, a potent vertebrate-active delta-conotoxin characterized from a vermivorous cone snail (Conus suturatus). SuVIA is equipotent at hNa(v)1.3, hNa(v)1.4 and hNa(v)1.6with EC(50)s in the low nanomolar range. SuVIA also increased peak hNa(v)1.7 current by approximately 75% and shifted the voltage-dependence of activation to more hyperpolarized potentials from -15 mVto -25 mV, with little effect on the voltage-dependence of inactivation. Interestingly, the proximal venom gland expression and pain-inducing effect of SuVIAinmammals suggest that delta-conotoxins in vermivorous cone snails play a defensive role against higher order vertebrates. We propose that delta-conotoxins originally evolved in ancestral vermivorous cones to defend against larger predators including fishes have been repurposed to facilitate a shift to piscivorous behaviour, suggesting an unexpected underlying mechanism for this remarkable evolutionary transition.