Protein allows poison dart frogs to accumulate toxins safely, study finds

Scientists have identified the protein that helps poison dart frogs safely accumulate their namesake’s toxins, according to a study published today in eLife. The findings resolve a long-standing scientific mystery and could suggest potential therapeutic strategies for treating humans poisoned by similar molecules.

Alkaloid compounds, like caffeine, make coffee, tea, and chocolate delicious and enjoyable to consume, but can be harmful in large amounts. In humans, the liver can safely metabolize modest amounts of these compounds. Tiny poison dart frogs consume many more toxic alkaloids in their diet, but instead of breaking down the toxins, they accumulate them in their skin as a defense mechanism against predators.

“How poison dart frogs can carry highly toxic alkaloids into their bodies without poisoning themselves has long been a mystery,” says lead author Aurora Alvarez-Buylla, a Ph.D. student in the Department of Biology at Stanford University in California, USA. “We aimed to answer this question by looking for proteins that could safely bind and transport alkaloids in the blood of poison dart frogs.”

Alvarez-Buylla and his colleagues used a compound similar to the poison frog alkaloid as a sort of “molecular hook” to attract and bind proteins in blood samples taken from the Diablito poison frog. The alkaloid-like compound was bioengineered to glow under fluorescent light, allowing the team to see proteins as they bind to this decoy.

Then they separated the proteins to see how each interacted with alkaloids in a solution. They discovered that a protein called alkaloid-binding globulin (ABG) acts like a “toxin sponge” that collects alkaloids. They also identified how the protein binds to alkaloids by systematically testing which parts of the protein were necessary to bind it successfully.

“The way ABG binds alkaloids has similarities to the way proteins that transport hormones in human blood bind to their targets,” says Alvarez-Buylla. “This finding could suggest that the frog’s hormone-handling proteins evolved the ability to handle alkaloid toxins.”

The authors say the similarities to human hormone-transporting proteins could provide a starting point for scientists to try to create human proteins that can mop up toxins. “If such efforts are successful, it could offer a new way to treat certain types of poisonings,” says lead author Lauren O’Connell, an assistant professor in the department of biology and a member of the Wu Tsai Neuroscience Institute at Stanford University. .

“Beyond the potential medical relevance, we have gained a molecular understanding of a fundamental part of poison frog biology, which will be important for future work on biodiversity and the evolution of chemical defenses in nature “, concludes O’Connell.