Key points:
- Researchers have filled a long-standing knowledge gap in the field of sensory biology—how mammals sense cold.
- The team has linked the sensation of cold to a protein called GluK2, primarily found on neurons in the brain but also expressed in sensory neurons in the peripheral nervous system.
- The new finding could have implications for human health and well-being, especially for those patients whom experience cold differently under disease conditions.
University of Michigan researchers have identified the protein that enables mammals to sense cold, filling a long-standing knowledge gap in the field of sensory biology. The findings could help unravel how we sense and suffer from cold temperature in the winter, and why some patients experience cold differently under particular disease conditions.
“Various studies have found the proteins that sense hot, warm, even cool temperatures—but we've been unable to confirm what senses temperatures below about 60 degrees Fahrenheit,” said senior author Shawn Xu, professor at the U-M Life Sciences Institute.
In a 2019 study, researchers in Xu's lab discovered the first cold-sensing receptor protein in Caenorhabditis elegans. Because that gene is evolutionarily conserved across many species—including mice and humans—the finding provided a starting point for verifying the cold sensor in mammals: a protein called GluK2 (short for Glutamate ionotropic receptor kainate type subunit 2).
For this latest study, published in Nature Neuroscience, researchers tested their hypothesis in mice that were missing the GluK2 gene, and thus could not produce any GluK2 proteins. Through a series of experiments to test the animals' behavioral reactions to temperature and other mechanical stimuli, the team found that the mice responded normally to hot, warm and cool temperatures, but showed no response to noxious cold.
“We now know that this protein serves a totally different function in the peripheral nervous system, processing temperature cues instead of chemical signals to sense cold,” said co-senior author of the study Bo Duan, U-M associate professor of molecular, cellular, and developmental biology.
While GluK2 is best known for its role in the brain, Xu speculates that this temperature-sensing role may have been one of the protein's original purposes. The GluK2 gene has relatives across the evolutionary tree, going all the way back to single-cell bacteria.
“This discovery of GluK2 as a cold sensor in mammals opens new paths to better understand why humans experience painful reactions to cold, and even perhaps offers a potential therapeutic target for treating that pain in patients whose cold sensation is overstimulated,” Xu said.