Cool-Temperature-Sensing Protein Found by TSRI Investigators

By Jason Socrates Bardi

A group of researchers from The Scripps Research Institute (TSRI) and the Genomics Institute of the Novartis Research Foundation (GNF) have identified and isolated a protein that mediates the body's ability to sense cold through the skin.

In an article that will appear in a March issue of the journal Cell, the group describes the protein, called TRPM8, which is the first cold-sensing molecule that has ever been identified and may be an important basic target for pain-modulating drugs.

"Everybody knows we feel cold, but it was not understood at the molecular level," says TSRI Assistant Professor of Cell Biology Ardem Patapoutian.

Humans and other vertebrate animals use specialized neurons to sense temperature, pressure, and other physical stimuli on the skin. These neurons are located in the spinal column and are connected to the skin and organs through long axons.

Expressed on the axons are the molecules that detect cold temperatures and other stimuli in these distant locations and relay the information back to the neurons.

The existence of specialized cold-neurons had been known for years, as had the existence of similar heat-sensing neurons. And some of the heat-detecting molecules were also known. But the actual molecules that sense cold temperatures and signal back to the neuron through the axon were a complete mystery.

The TSRI group identified and cloned an ion channel, TRPM8, which is the first-known signaling molecule that helps the body sense cold temperatures. The channel becomes activated below 25° C and opens, allowing an influx of calcium ions into the axon, an electrical signal that alerts the neuron, which relays the message to the brain.

"These channels respond directly to cold temperature," says Patapoutian. "[And] they offer interesting insight into the fundamental biology of cold perception."

Interestingly, the channels also respond to menthol, the "cooling" flavoring and balm additive. The use of mentholated rubs for pain relief would suggest that the TRPM8 ion channels play a role in pain sensing as well. One interesting possible application would be the search for chemicals that modulate the signaling response.

Patapoutian says that there are likely more cold-sensing molecules, and these findings open the road to identifying other channels and receptors for the mediation of cold sensation.

The research article "A TRP channel that senses cold stimuli and menthol" is authored by Andrea M. Peier, Aziz Moqrich, Anne C. Hergarden, Alison J. Reeve, David A. Andersson, Gina M. Story, Taryn J. Earley, Ilaria Dragoni, Peter McIntyre, Stuart Bevan, and Ardem Patapoutian and appears in the March 8, 2002 issue of Cell.

The research was funded by a grant to TSRI from Novartis.




TSRI Assistant Professor Ardem Patapoutian's group identified and cloned an ion channel, TRPM8, which is the first-known signaling molecule to help the body sense cold temperatures. Photo by Jason S. Bardi.