The molecule that lets snakes sense heat is the same one that makes wasabi feel fiery.
Scientists have known for decades that some snakes use specialized holes called pit organs to “see” the heat radiating from prey. Now, molecular biologists have pinpointed the protein that gives pit-bearing snakes — vipers, boas and pythons — this sixth sense. The culprit is called TRPA1, a protein whose human counterpart is known as the “wasabi receptor” for its role in sensing the potent condiment. The results are reported online March 14 in Nature.
“This is one of the first really interesting new findings in that species” in 20 years, comments snake-sense specialist Ken Catania of Vanderbilt University in Nashville, who was not associated with the study. “It’s the kind of paper that makes me have to go and revise my class lectures.”
Scientists had thought that snakes’ sensitivity to heat comes from the exceptionally thin tissue in pit organs. Just as it takes less heat to boil a cup of water than a pot, it takes less heat to stimulate pit organ tissue than a mammal’s skin. But what was happening on a molecular level had never been explored.
“We’ve been trying to address this question for a long time, several years,” says study coauthor David Julius of the University of California, San Francisco. “The technology wasn’t really right for us to do that until recently.” Recent advances in high-throughput genetic screening that can sift through hundreds of genes quickly made the study possible.
Julius and his colleagues had previously investigated the molecules that make chili peppers feel hot or menthol feel cool. They found that a family of proteins called TRP ion channels were in charge of sensing temperature and chemical irritants for creatures as complicated as humans or as simple as fruit flies.
The team noted that clumps of nerve cells called trigeminal ganglia in pit vipers’ heads were larger and more complex than the corresponding cells in mammals. The cells also sent most of their nerve fibers directly to the heat sensors. “It’s almost like a big pipe that just goes boom, right to the pit organ,” Julius says. So the researchers searched for genes that were expressed in the trigeminal ganglia but not in similar nerve cells in the snakes’ tails.
Although the researchers suspected that the TRP channels might be the heat sensors they sought in snakes, or at least an accomplice, they did a nearly blind search to avoid favoring their leading candidate.
To the team’s surprise, only one gene stood out: the TRPA1 gene. The gene that produces the TRPA1 protein was 400 times more active in the nerves of the head than the nerves of the body.
“It was very pleasing to see that this one molecule was a member of the TRP channel family,” Julius says, “but it wasn’t exactly the channel we thought it would be.”
To check that they had nabbed the right protein, Julius and his colleagues grew cells that expressed the TRPA1 gene in the lab. They then raised the temperature to see if the cells showed any electric or chemical response to heat.
In rattlesnakes, they found, the gene for TRPA1 kicked on at about 28 degrees Celsius, below typical body temperatures for mammals — or as snakes know them, prey. “That said yes, this definitely responds to heat,” Julius says. In boas and pythons, whose heat sensors are known to be less sensitive than rattlesnakes’, the proteins responded at about 30 degrees and 33 degrees, respectively.
Understanding how TRP channels work in different species could have implications for building thermal sensors for military uses or drugs to treat chronic pain, Julius says. “There are bioengineers who are interested in these processes, and drug companies who want to know how to modify these channels,” he says.
