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.
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