CONE SNAIL VENOM MOVIE

The venom duct shows a corresponding regionalization of toxin production, with high levels of defence-evoked and predation-evoked venoms in the proximal and distal sections, respectively. In contrast, the predation-evoked venom appears largely devoid of these paralytic toxins. The defence-evoked venom typically comprises paralytic toxins, previously thought to participate in prey capture, that explain the symptoms associated with human envenomation. In this article, we report for the first time the remarkable ability of cone snails to rapidly and reversibly switch between functionally and structurally distinct venoms in response to predatory or threatening stimuli.

Such deleterious effects are currently explained by a unique venom that acts on targets with conserved pharmacology across prey and predator, and a separately evolved defensive strategy to deter aggressors has not been investigated previously. The defensive use of venom can also result in human injuries, with Conus geographus stings producing confirmed fatalities 5.

CONE SNAIL VENOM MOVIE

2), possibly by using their venom defensively (see Supplementary Movie 2). While a shell can serve as the first line of defence, repair marks commonly observed in many Conus species indicate they can survive physically damaging attacks from predators such as octopus or fish (see Supplementary Fig. Molecular and phylogenetic studies have demonstrated that the evolution of envenomation strategies is typically a predatory rather than a defensive adaptation 7, 8, despite the critical importance of defence for animal survival 9. geographus predation is unclear, since it mainly uses an alternate ‘nirvana cabal’ to sedate fish prior to capture using a net strategy (see Supplementary Fig.

However, the role of the paralytic motor cabal in C. geographus comprises inhibitory ω-, μ- and α-conotoxins that target neuromuscular receptors and produce flaccid paralysis in fish 5. In contrast, the ‘motor cabal’ developed in particular by C. For example, the ‘lightning-strike cabal’ comprises potassium channel blocking κ-conotoxins and excitatory sodium channel modifying δ-conotoxins that produce immediate tetanic paralysis in fish 2. To maximize venom potency, cone snails deploy synergistic groups of conotoxins, known as ‘cabals’ 4. This strategy is underpinned by a remarkable diversity of conotoxins that target a wide range of membrane proteins, including the FDA-approved Ca v2.2 inhibitor ω-MVIIA (Prialt) used to treat intractable pain 3. Utilizing a hollow, harpoon-like radula, cone snails inject a complex cocktail of potent venom peptides (conotoxins) to rapidly immobilize the prey 2. Venomous marine gastropods of the genus Conus have evolved one of the most sophisticated envenomation strategies known, allowing these slow animals to capture worms, mollusks and even fish 1. We propose that defensive toxins, originally evolved in ancestral worm-hunting cone snails to protect against cephalopod and fish predation, have been repurposed in predatory venoms to facilitate diversification to fish and mollusk diets. A specialized defensive envenomation strategy is widely evolved across worm, mollusk and fish-hunting cone snails. Predation- and defence-evoked venoms originate from the distal and proximal regions of the venom duct, respectively, explaining how different stimuli can generate two distinct venoms.

geographus predation-evoked venom contains prey-specific toxins mostly inactive at human targets. Here, we show that the defence-evoked venom of Conus geographus contains high levels of paralytic toxins that potently block neuromuscular receptors, consistent with its lethal effects on humans. Remarkably, cone snails can rapidly switch between distinct venoms in response to predatory or defensive stimuli. Venomous animals are thought to inject the same combination of toxins for both predation and defence, presumably exploiting conserved target pharmacology across prey and predators.

Cone snail venom