Scorpion toxin targets the 'wasabi receptor'


And that may help solve mystery of chronic pain.


The Black Rock Scorpion can bring on a wasabi moment.
Mark Norman / Museums Victoria

There’s more ammunition for those who say Australia is the home of creepy crawlies that can do you harm.

A systematic search for animal venom that can trigger what’s known as the “wasabi receptor” has led scientists to the Black Rock Scorpion (Urodacus manicatus).

It lives in cleared areas beneath rocks or logs in burrows around the east of mainland Australia.

Its toxin targets a chemical-sensing protein found in nerve cells (officially known as TRPA1) that's responsible not only for the sinus-jolting sting of wasabi, but also the flood of tears associated with chopping onions.

And that’s worth knowing, say researchers from the University of California, San Francisco, US, and Australia’s University of Queensland, because it will help in the study of chronic pain and inflammation, and possibly lead to the development of new non-opioid pain relievers.

"Think of TRPA1 as the body's 'fire alarm' for chemical irritants in the environment," says UCSF’s John Lin King, lead author of a paper published in the journal Cell.

"When this receptor encounters a potentially harmful compound – specifically, a class of chemicals known as reactive electrophiles, which can cause significant damage to cells – it is activated to let you know you're being exposed to something dangerous that you need to remove yourself from."

Smoke and pollutants are rich in reactive electrophiles that can trigger TRPA1 in the cells that line the surface of the body's airway, which can induce coughing fits and sustained airway inflammation.

The receptor can also be activated by chemicals in pungent foods like wasabi, onions, mustard, ginger and garlic – compounds that, according to Lin King, may have evolved to discourage animals from eating these plants.

What he and his colleagues have dubbed the scorpion’s "wasabi receptor toxin" (WaTx) appears to have evolved for the same reason.

Most animals, from worms to humans, have some form of TRPA1, but the researchers found that WaTx can only activate the version found in mammals, which aren't on the menu for Black Rock scorpions, suggesting that the toxin is mainly used to ward off predators.

"Our results provide a beautiful and striking example of convergent evolution, whereby distantly related life forms – plants and animals – have developed defensive strategies that target the same mammalian receptor through completely distinct strategies," says senior author David Julius, from UCSF.

What’s even more interesting, the researchers say, is WaTx ‘s modus operandi.

Most compounds are either ingested by a cell through a complex process known as endocytosis or pass through one of the many protein channels that stud its surface and act as gatekeepers.

But WaTx contains an unusual sequence of amino acids that allows it to simply penetrate the cell's membrane and pass right through to the cell's interior.

"This is unusual for peptide toxins," Lin King says, "but it's also exciting because if you understand how these peptides get across the membrane, you might be able to use them to carry things – drugs, for example – into the cell that can't normally get across membranes."

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  1. https://collections.museumvictoria.com.au/species/8761
  2. https://collections.museumvictoria.com.au/species/8761
  3. https://www.cell.com/cell/fulltext/S0092-8674(19)30779-2
  4. https://www.sciencedirect.com/topics/neuroscience/endocytosis
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