Toxins enable venomous animals can be outstanding predators with impressive attack and have defence capabilities. They can fulfil various ecological interactions by toxins, including prey capture, defense against predators, and aggressive encounters.

However, toxins act as a double-edged sword. The venom gland not only functions as an arsenal in which to secrete, store and manage toxin molecules, but also physiologically isolates venom from other tissues. Venomous animals has there own receptors to avoid self-intoxication.

The receptors expressed in the venom gland may possess a unique resistance mechanism with tissue specificity. The receptors expressed in the venom gland are trapped in a toxin-rich environment, stil can perform their physiological roles unhindered.

A research group led by Prof. LAI Ren from the Kunming Institute of Zoology of the Chinese Academy of Sciences has recently performed a comprehensive study of the venom resistance mechanism in centipedes. The study was published online in Current Biology on July 20.

Researchers showed that the mechanism of tissue-specific resistance in centipedes (Scolopendra subspinipes mutilans). The results demonstrated that a splice variant of KCNQ1 has been employed specifically by the venom gland rather than by other tissues. In the venom gland, the KCNQ1 splice variant has distributed on the canal cells, which can form conducting ducts between gland units and the common venom ducts. Due to the alternative splicing, the KCNQ1 splice variant can repel SsTx, which is a key toxin for defence and preying in the venom gland. Establishing a safe zone in the venom-storing/secreting environment by exhibiting a buried state at the binding site of SsTx, .

“We noticed that the origin of SsTx-like toxins might manipulate the evolutionary process of at least two receptors. Centipede Shaker gene introduced a mutation on exon 3, which can encode an arginine at the outer pore and provide a repulsion force for SsTx-Shaker interaction. It was observed the mutation without tissue-specificity in all Shaker transcripts. Meanwhile, the centipede KCNQ1 gene has regulated by alternatively splicing in the venom gland, suggesting a wide-array of resistance mechanisms to cope with the toxin-rich environment,” said Dr. WANG Yunfei, first author of the study.

The study has further confirm that the alternative splicing of receptors is a general strategy, which is likely also employed by other venomous animals to enable toxin resistance.