Animal venoms are powerful, highly evolved chemical weapons for defense and predation. While venoms are used mainly to lethally antagonize heterospecifics (individuals of a different species), nonlethal envenomation of conspecifics (individuals of the same species) is occasionally observed. Both the venom and target specifications underlying these two forms of envenomation are still poorly understood. As an excellent model to understand the molecular basis of venom use for survival strategies, a centipede may directly inject venom into individuals of the same species (FIGURE 1A-C) for intraspecific competition as a warning signal without involving other defensive strategies such as aposematism or chelae.

Recently, researchers from Kunming Institute of Zoology and their collaborators reported a target-switching mechanism in centipede, which enables a single toxin to develop graded intraspecific and interspecific antagonistic interactions.

In this study, they determined that the Shal channel of S. subspinipes serves as the main target for intraspecific competition or deterrence. Peptide neurotoxins block the specialized Shal channel (FIGURE 1D-G) to induce neuronal hyperexcitation and vascular constriction, which further cause a nonlethal and short-term paralysis within 10 min (FIGURE 1B). In addition, most receptors (such as Shaker) are resistant to centipede venom using mutations to repel toxin components (FIGURE 1H), thus avoiding lethality among conspecifics. On the basis of this target-switching mechanism, a major toxin component [Ssm Spooky Toxin (SsTx)] in centipede venom inhibits the Shal channel in conspecifics but not in heterospecifics to cause short-term, recoverable, and nonlethal envenomation. This same toxin causes fatal heterospecific envenomation, for example, by switching its target to the Shaker channels in heterospecifics without inhibiting the Shaker channel of conspecific S. subspinipes individuals.

In combination with their previous studies, they have partially drawn the mechanistic insights for several important survival strategies of centipede (FIGURE 1I). Specifically, (i) centipede’s Shal channel evolved to establish a unique toxin-target interaction, which serves as the mechanism for eliciting nonlethal warning signal to conspecifics; (ii) SsTx-induced immobilization is likely due to the inhibition of centipede’s Shal channel in motoneurons, which leads to an enhanced excitation in these neurons; (iii) most of physiological receptors, such as Shaker, TRPV1 (transient receptor potential vanilloid 1), and KCNQ channels of centipede, are expected to coevolve with the venom system to resist against their own venom components; and (iv) multiple receptors of heterospecifics including Shaker, KCNQ, and TRPV1 channels are efficiently modulated by centipede toxins,

The results show that Venomous individuals take full advantage of optimized chemical weapons to interact with other participants in their niches by identifying self and non-self. Therefore, as a consequence of coevolution between venom components and receptors, this study reveals that the target-switching mechanism is used against different opponents by venomous animals to exhibit a flexible and low-cost antagonistic strategy.

The study entitled “Target switch of centipede toxins for antagonistic switch” has been published in Science Advances(https://advances.sciencemag.org/content/6/32/eabb5734). 

This work was financially supported by funding from the National Science Foundation of China,Chinese Academy of Sciences, and Yunnan Province. 

(Imaged by YANG Shilong and LAI Ren)

FIGURE 1. The target-switching mechanism in centipede. (A) Photograph of the S. subspinipes self-envenomation. These centipedes inject venom to each other during intraspecific interaction. (B) Movement distance recorded per minute following injection of 10 μl of crude venom or saline. (C) Images of the S. subspinipes and the isolated DUM neuron. (D-F) Whole-cell DUM calcium (D), sodium (E), and potassium (F) currents challenged by crude venom (1 mg/ml), 20 μM verapamil, 25 μM Ni+, 1 μM TTX, and 100 mM TEA, respectively. (G) The salt bridge formed between SsTx K17 and Shal E351 was indicated in SsTx-Shal structural model. (H) Representative whole-cell recordings of centipede Shaker (left) and single-point channel mutant (right) in the presence of crude venom (1 mg/ml) or 1 μM SsTx. (I) Schematic diagram summarizing the target-switching mechanism in centipede survival strategy of both intraspecific and interspecific interaction. Target specifications (Shal, Shaker, TRPV1, and KCNQ channels) underlying the envenomation of conspecifics and heterospecifics are shown. Representative point mutations of species-specific Shal and Shaker channels are differentiated in conspecifics and heterospecifics.

(Image adopted from Fig. 2-4 of the published paper)