Neuroscientists at the University of Michigan have identified a thermoreceptor that mediates cold sensing in somatosensory neurons.
GluK2 KO mice are defective in cold sensing. Image credit: Cai et al., 10.1038/s41593-024-01585-8.
“The field started uncovering these temperature sensors over 20 years ago, with the discovery of a heat-sensing protein called TRPV1,” said University of Michigan’s Professor Shawn Xu.
“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 15 degrees Celsius (60 degrees Fahrenheit).”
In 2019, scientists discovered the first cold-sensing receptor protein in Caenorhabditis elegans, a species of millimeter-long worms that the lab studies as a model system for understanding sensory responses.
Because the gene that encodes the Caenorhabditis elegans protein is evolutionarily conserved across many species, including mice and humans, that finding provided a starting point for verifying the cold sensor in mammals: a protein called Glutamate ionotropic receptor kainate type subunit 2 (GluK2).
In a new study, Professor Xu and colleagues 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, they found that the mice responded normally to hot, warm and cool temperatures, but showed no response to noxious cold.
GluK2 is primarily found on neurons in the brain, where it receives chemical signals to facilitate communication between neurons.
But it is also expressed in sensory neurons in the peripheral nervous system (outside the brain and spinal cord).
“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 University of Michigan’s Dr. Bo Duan.
The GluK2 gene has relatives across the evolutionary tree, going all the way back to single-cell bacteria.
“A bacterium has no brain, so why would it evolve a way to receive chemical signals from other neurons?” Professor Xu said.
“But it would have great need to sense its environment, and perhaps both temperature and chemicals.”
“So I think temperature sensing may be an ancient function, at least for some of these glutamate receptors, that was eventually co-opted as organisms evolved more complex nervous systems.”
The results appear in the journal Nature Neuroscience.
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W. Cai et al. The kainate receptor GluK2 mediates cold sensing in mice. Nat Neurosci, publsihed online March 11, 2024; doi: 10.1038/s41593-024-01585-8
Source : Breaking Science News