Specialized protein helps these ground squirrels resist the cold

The hardy souls who manage to push shorts season into December might feel some kinship with the thirteen-lined ground squirrel.

The critter hibernates all winter, but even when awake, it’s less sensitive to cold than its nonhibernating relatives, a new study finds. That cold tolerance is linked to changes in a specific cold-sensing protein in the sensory nerve cells of the ground squirrels and another hibernator, the Syrian hamster, researchers report in the Dec. 19 Cell Reports. The altered protein may be an adaptation that helps the animals drift into hibernation.

In experiments, mice, which don’t hibernate, strongly preferred to hang out on a hot plate that was 30° Celsius versus one that was cooler. Syrian hamsters (Mesocricetus auratus) and the ground squirrels (Ictidomys tridecemlineatus), however, didn’t seem to notice the chill until plate temperatures dipped below 10° Celsius, notes study coauthor Elena Gracheva, a neurophysiologist at Yale University.

Further work revealed that a cold-sensing protein called TRPM8 wasn’t as easily activated by cold in the squirrels and hamsters as in rats. Found in the sensory nerve cells of vertebrates, TRPM8 typically sends a sensation of cold to the brain when activated by low temperatures. It’s what makes your fingertips feel chilly when you’re holding a glass of ice water. It’s also responsible for the cooling sensation in your mouth after you chew gum made with menthol.

The researchers looked at the gene that contains the instructions to make the TRPM8 protein in ground squirrels and switched up parts of it to find regions responsible for tolerance to cold. The adaptation could be pinned on six amino acid changes in one section of the squirrel gene, the team found. Cutting-and-pasting the rat version of this gene fragment into the squirrel gene led to a protein that was once again cold-sensitive. Hamster TRPM8 proteins also lost their cold tolerance with slightly different genetic tweaks in the same region of the gene.

The fact that it’s possible to make a previously cold-resistant protein sensitive to cold by transferring in a snippet of genetic instructions from a different species is “really quite striking,” says David McKemy, a neurobiologist at the University of Southern California in Los Angeles.

As anyone who’s lain awake shivering in a subpar sleeping bag knows, falling asleep while cold is really hard. Hibernation is different than sleep, Gracheva emphasizes, but the squirrels and hamsters’ tolerance to cold may help them transition from an active, awake state to hibernation. If an animal feels chilly, its body will expend a lot of energy trying to warm up — and that’ll work against the physiological changes needed to enter hibernation. For example, while hibernating, small mammals like the ground squirrel slow their pulse and breathing and can lower their core body temperature to just a few degrees above freezing.

Modifications to TRPM8 probably aren’t the only factors that help ground squirrels ignore the cold, Gracheva says, especially as the thermometer drops even closer to freezing. “We think this is only part of the mechanism.”

Scientists also aren’t sure exactly how TRPM8 gets activated by cold in the first place. A detailed view of TRPM8’s structure, obtained using cryo-electron microscopy, was published by a different research group online December 7 in Science. “This is a big breakthrough. We were waiting for this structure for a long period of time,” Gracheva says. Going forward, she and colleagues hope that knowing the protein’s structure will help them link genetic adaptations for cold tolerance in TRPM8 with specific structural changes in the protein.