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Forscher identifizieren kälteempfindliches Protein bei Säugetieren

von NFI Redaktion

Researchers from the University of Michigan have identified the protein that enables mammals to sense cold, filling a long-standing gap in sensory biology.

The findings, published in Nature Neuroscience, could help uncover how we perceive and suffer from cold during winter, and why some patients experience cold differently in certain medical conditions.

„The discovery of these temperature sensors started over 20 years ago with the identification of a heat-sensitive protein called TRPV1.“


Shawn Xu, neuroscientist, Professor at UM Life Sciences Institute and lead author of the new research

„Various studies have found that proteins can perceive hot, warm, and even cool temperatures – but we could not confirm what temperatures below about 60 degrees Fahrenheit are being perceived.“

In a 2019 study, researchers in Xu’s lab discovered the first cold-sensitive receptor protein in Caenorhabditis elegans, a type of millimeter-long worms used as a model system in the lab to understand sensory reactions.

Since the gene encoding the C. elegans protein is conserved in many species, including mice and humans, this 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, a research team from the Life Sciences Institute and the UM College of Literature, Science, and the Arts tested their hypothesis on mice lacking the GluK2 gene, thus unable to produce GluK2 proteins. Through a series of experiments testing the animals‘ behavioral responses 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 harmful cold.

GluK2 is mainly present in neurons in the brain, where it receives chemical signals to facilitate communication between neurons. However, it is also expressed in sensory neurons in the peripheral nervous system (outside the brain and spinal cord).

„We now know that this protein has a completely different function in the peripheral nervous system, processing temperature signals instead of chemical signals to perceive cold.“


Bo Duan, Associate Professor of Molecular, Cellular, and Developmental Biology at UM and Co-Senior Author of the study

While GluK2 is known primarily for its role in the brain, Xu speculates that its role as a temperature sensor may have been one of the protein’s original purposes. The GluK2 gene has relatives throughout the evolutionary tree, dating back to single-celled bacteria.

„A bacterium doesn’t have a brain. Why would it develop a way to receive chemical signals from other neurons? But it would definitely need to perceive its environment, perhaps both temperature and chemicals,“ said Xu, who is also a Professor of Molecular and Integrative Physiology at the UM Medical School. „So, I think temperature sensing could be an ancient function for some of these glutamate receptors, eventually taken over as organisms developed more complex nervous systems.“

Xu believes that the new findings not only fill a gap in the mystery of temperature sensing but could also have implications for human health and well-being. For example, cancer patients undergoing chemotherapy often experience painful reactions to cold.

„The discovery of GluK2 as a cold sensor in mammals opens new avenues to better understand why people feel painful reactions to cold, and may even offer a potential therapeutic target for treating these pains in patients whose cold perception is overstimulated,“ Xu said.

The research was supported by the National Institutes of Health. All procedures conducted on mice were approved by the Institutional Animal Care and Use Committee and performed in accordance with institutional guidelines.

Source:

Journal Reference:

Cai, W., et al. (2024). The Kainate receptor GluK2 mediates cold perception in mice. Nature Neuroscience. doi.org/10.1038/s41593-024-01585-8.

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