How do arrowhead frogs store poison in their bodies without poisoning themselves?

A recent study published in eLife has decoded how poison dart frogs safely accumulate their signature toxins. This research, which solves a long-standing scientific mystery, could lead to the development of antidotes to treat people poisoned with similar molecules.

Alkaloid compounds like caffeine make coffee, tea, and chocolate delicious and pleasant to consume, but can be harmful in large quantities. In humans, the liver can safely metabolize small 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.

Aurora Alvarez-Buylla, a doctoral student in the Department of Biology at Stanford University in California, USA and lead author of the study, explains: “It has always been a mystery how poison dart frogs can transport alkaloids that are highly toxic to their bodies without poisoning themselves.” This The team searched for proteins that can safely bind and transport alkaloids in the blood of poison dart frogs.

To do this, they used a compound similar to poison frog alkaloid as a “molecular bait” to attract and bind to proteins in Diablito poison frog blood samples. This alkaloid-like compound was converted to glow under fluorescent light, allowing the team to see the proteins as they bound to this decoy.

It has always been a mystery how poison dart frogs can transport highly toxic alkaloids throughout their bodies without poisoning themselves.

They then separated the proteins to see how each one interacted with alkaloids in a solution. They discovered that a protein called alkaloid-binding globulin (ABG) acts as a “toxin sponge” that absorbs alkaloids. They also identified how the protein binds to alkaloids by systematically testing which parts of the protein are necessary for successful binding.

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“The way ABG binds to alkaloids is similar to the way hormone-carrying proteins in human blood bind their targets,” explains Alvarez-Buylla. “This discovery may indicate that the frog’s hormone-regulating proteins have evolved the ability to deal with alkaloid toxins.”

The authors suggest that the similarities to human proteins that transport hormones could provide a starting point for scientists to try to bioengineer human proteins that can “absorb” toxins. “If such efforts are successful, it could provide a new way to treat certain types of poisoning,” says senior 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 achieved 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.


Binding and sequestration of poison frog alkaloids by a plasma globulin.

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