Scientists have discovered a “toxin sponge” protein in poison dart frogs that safely stores dangerous alkaloids, offering the possibility of a new approach to treating poisoning in humans. (Artist’s concept) Credit: SciTechDaily.com
The newly identified protein helps poison dart frogs accumulate and store powerful toxins in their skin that they use in self-defense against predators.
Scientists announced that they have identified a protein that helps poison dart frogs safely accumulate their namesake toxin, according to a study published Dec. 19 in the journal Nature. e-life.
The discovery solves a long-standing scientific mystery and could suggest potential therapeutic strategies to treat humans addicted to similar molecules.
Alkaloids: from coffee to frog skin
Alkaloid compounds such as caffeine make coffee, tea, and chocolate delicious and comforting, but they can be harmful if consumed in large amounts. In humans, the liver can safely metabolize moderate amounts of these compounds. Small poison dart frogs ingest far more toxic alkaloids in their diet, but instead of breaking them down, they accumulate them in their skin as a defense mechanism against predators.
“It has long been a mystery how poison dart frogs are able to transport highly toxic alkaloids into their bodies without being poisonous themselves,” said lead author and doctoral student in the Department of Biology at Stanford University in California, USA. Aurora Álvarez Buira says. “We aimed to answer this question by searching for proteins that could bind and safely transport alkaloids in poison dart frog blood.”
Diablito poison dart frog, Uofaga Silvatica, native to Colombia and Ecuador. Credit: Marie-Therese Fischer (CC BY 4.0)
Uncover the secrets of frogs
Alvarez-Buylla and colleagues used compounds similar to poison dart frog alkaloids as a kind of “molecular fishing hook” to attract and bind proteins in blood samples taken from poison dart frogs. The alkaloid-like compounds were bioengineered to glow under fluorescent lights, allowing the researchers to watch proteins bind to the decoys.
They then separated the proteins to see how each protein interacted with the alkaloids in solution. They discovered that a protein called alkaloid-binding globulin (ABG) acts like a “toxin sponge” that collects alkaloids. They also identified how proteins bind to alkaloids by systematically testing which parts of the protein are needed to successfully bind the alkaloids.
Impact on humans and future research
“The way that ABG binds to alkaloids is similar to the way that proteins that transport hormones in human blood bind to their targets,” Álvarez Buira explains. “This finding may suggest that hormone-processing proteins in frogs have evolved the ability to manage alkaloid toxins.”
The authors say the similarities with human hormone transport proteins could be a starting point for scientists to try bioengineering human proteins that “sponge” with toxins. “If successful, these efforts could provide new ways to treat certain addictions,” said lead author Lauren O’Connell, an assistant professor of biology at Stanford University and a member of the Wu Tsai Institute for Neuroscience. he says.
“Beyond potential medical relevance, we have achieved a molecular understanding of a fundamental part of poison dart frog biology, which will inform future research on biodiversity and the evolution of natural chemical defenses.” “This will be important for research,” concludes O’Connell.
Reference: “Binding and isolation of poison dart frog alkaloids” plasma Aurora Alvarez Buira, Marie Therese Fisher, Maria Dolores Moya Garzon, Alexandra E. Rangel, Elisio E. Tapia, Julia T. Tanzo, H. Tom So, Luis A. Coloma, Written by Jonathan Z. Long and Lauren A. O’Connell, December 19, 2023. e-life.
DOI: doi:10.7554/eLife.85096
Funding: National Science Foundation, New York Stem Cell Foundation, National Science Foundation Graduate Research Fellowship Program, Howard Hughes Medical Institute, Alfonso Martín Escudero Foundation, Wu Tsai Human Performance Alliance.
Source: scitechdaily.com
