Navigation Links
Molecular thermometers on skin cells detect heat and camphor

The human brain is like a general in a bunker. Floating in its bubble of cerebrospinal fluid, it has no direct window to the outside world, so the only way for the brain to observe, comprehend, and order the body into action is to rely on information it receives. This information comes to it through a sophisticated system of sensory neurons that connect the brain to organs like the eye, ear, nose, and mouth.

In recent years, biologists and neuroscientists have been trying to discover the basic molecules and mechanisms that underlie this complicated communication system that is our senses, and one group of researchers from The Scripps Research Institute and the Genomics Institute of the Novartis Research Foundation (GNF), has been making headway in trying to understand those that mediate our sense of touch.

Touch is perhaps the most fundamental of our five senses because it works through our largest organ, the skin. Through the skin we can detect temperature, texture, and understand both pleasure and pain.

A few years ago, the Scripps Research and GNF team, which was led by Scripps Research Assistant Professor Ardem Patapoutian, was the first to clone a protein (TRPV3) that the researchers believed was involved in our ability to sense and detect warm temperature.

But while temperature-gated action of TRPV3 suggested the protein might be communicating temperature to the brain, its distribution raised some doubts. Despite expectations that temperature sensors be present in sensory neurons innervating the skin, TRPV3 protein was found in actual skin cells (keratinocytes) and not in the neurons.

Now, in the latest issue of the journal Science, the team is reporting definitive evidence that TRPV3 is indeed a temperature sensor. They have demonstrated that mice lacking the TRPV3 protein have specific deficiencies in their ability to detect temperatures.

"Are the TRPV3 proteins involved in heat sensation in the living mammal?" says Patapoutian. "The answer seems to be 'yes.'"

This is significant because it suggests that TRPV3 is a potential drug target. TRPV3 is one of many receptors that participate in signaling pain--an indication for which there is a great need for new therapeutics.

Indeed, several compounds that are currently under investigation for alleviating chronic pain target the action of a protein called TRPV1 (VR1), which is similar to TRPV3.

Molecular Thermometers

TRPV3 and TRPV1 are both proteins that belong to a class of molecules known as "transient receptor potential" channels. There are at least six of these TRP channel proteins in humans and other mammals, and there has been growing evidence in the last few years that these proteins are "molecular thermometers" that detect hot and cold temperatures through the skin and communicate the sensation of temperature to the brain.

The most obvious evidence is that TRP channels are activated by thermal heat within a particular temperature range--from the extremely cold to the extremely hot. TRPV3, for instance, becomes activated at warm and hot temperatures of 33° C (91.5° F) and above. Similarly, other TRP channels are specifically activated within hot, warm, cool, or cold temperature ranges.

Most of these temperature-gated channels are also located where scientists would expect the molecules that communicate temperature to the brain to be located--in the sensory neurons that connect the skin to the spinal column and the brain. These proteins become activated when they receive the correct stimuli (such as a certain temperature), and this causes them to open and allow electrically charged ions to pass through and cause an electrical potential that signals the brain.

Patapoutian and his colleagues discovered TRPV3 a few years ago by conducting a computer search through an early-assembled draft of the human genome. Its sequence similarity to other temperature-gated proteins l ed them to identify and clone TRPV3 as a possible molecular thermometer--perhaps the first one that makes skin cells able to sense warm temperatures.

Now they have demonstrated that the receptor does indeed detect heat by examining the physiological and behavioral characteristics of a knockout mouse with no TRPV3 proteins. The mice appear completely normal behaviorally except that they have severe deficiencies in their ability to detect warm and hot temperatures. Patapoutian and his colleagues also showed that, in cultured keratinocyte cells, TRPV3 is activated by the compound camphor, which is one of the main ingredients in many warming rubs. TRPV3 is the first known receptor for camphor.

Significantly, when Patapoutian and his colleagues discovered TRPV3 a few years ago, they were intrigued to discover that it is unique among thermoTRP channels in that it is expressed on the surface of skin cells known as keratinocytes. At the time, they hypothesized that its presence on keratinocytes might mean that the detection of temperature takes place in the skin as well as on these neurons.

In their Science paper, they demonstrate that this is indeed the case by showing that camphor activates TRPV3 on keratinocytes but not on sensory neurons. In the knockout models, this heat- and camphor-mediated activity disappears, which suggests that it is the TRPV3 proteins on the keratinocytes that are actually detecting warm temperatures. It is not known how this signal is communicated to the brain, since keratinocytes, unlike neurons, have no direct link with the central nervous system. Keratinocytes do, however, touch nerve fibers, and it may be through these contacts that the signals are communicated. Investigations into this possibility are ongoing.


To read the article, "Impaired Thermosensation in Mice Lacking TRPV3, a Heat and Camphor Sensor in the Skin" by Aziz Moqrich, Sun Wook Hwang, Taryn J. Earley, Matt J. Petrus, Amber N. Murray , Kathryn S. R. Spencer, Mary Andahazy, Gina M. Story, and Ardem Patapoutian, see the March 4, 2005 issue of the journal Science or go to

This work was supported by grants from the National Institute of Neurological Disorders and Stroke, a National Research Service Award postdoctoral fellowship from the National Institutes of Health, the Damon Runyon Cancer Research Foundation, and by the Genomics Institute of the Novartis Research Foundation.


Source:Scripps Research Institute

Related biology news :

1. Molecular biology fills gaps in knowledge of bat evolution
2. Molecular machine may lead to new drugs to combat human diseases
3. Molecular Motors Cooperate In Moving Cellular Cargo, Study Shows
4. Molecular models advance the fight against malaria
5. Molecular fossils uncover link between viruses and the immune system
6. Molecular messengers perform a crucial role in the ability of injured nerve cells to heal themselves
7. Molecular steps involved in the creation of gene-silencing microRNAs identified
8. Molecular miners find pain relief drugs from the sea
9. Molecular mechanism of feather formation found
10. Molecular trigger for Huntingtons disease found
11. Molecular Partners Required For Appropriate Neuronal Gene Repression
Post Your Comments:

(Date:10/27/2015)... -- Munich, Germany , October ... automatically maps data from mobile eye tracking videos created ... that they can be quantitatively analyzed with SMI,s analysis ... , October 28-29, 2015. SMI,s Automated Semantic Gaze ... tracking videos created with SMI,s Eye Tracking Glasses ...
(Date:10/26/2015)... 2015  Delta ID Inc., a company focused on ... PC devices, announced its ActiveIRIS® technology powers the iris ... launched by NTT DOCOMO, INC in Japan ... smartphone to include iris recognition technology, after a very ... in May 2015, world,s first smartphone to have this ...
(Date:10/22/2015)...  Synaptics (NASDAQ: SYNA ), a leading developer of human ... September 30, 2015. --> --> ... 66 percent over the comparable quarter last year to $470.0 million. ... million, or $0.62 per diluted share. --> ... of fiscal 2016 grew 39 percent over the prior year period ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... ... November 24, 2015 , ... International Society for ... of the premier annual events for pharmaceutical manufacturing: 2015 Annual Meeting. The conference ... ISPE hosted the largest number of attendees in more than a decade. ...
(Date:11/24/2015)... , ... November 24, 2015 , ... The Academy of ... Interest Group (SIG), MultiGP, also known as Multirotor Grand Prix, to represent the First–Person ... few years. Many AMA members have embraced this type of racing and several new ...
(Date:11/24/2015)... FRANCISCO , Nov. 24, 2015  Twist ... announced that Emily Leproust, Ph.D., Twist Bioscience chief ... Jaffray Healthcare Conference on December 1, 2015 at ... Hotel in New York City. --> ... . Twist Bioscience is on Twitter. ...
(Date:11/24/2015)... , Nov. 24, 2015 Capricor Therapeutics, ... focused on the discovery, development and commercialization of first-in-class ... Chief Executive Officer, is scheduled to present at the ... at 10:50 a.m. EST, at The Lotte New York ... . . --> ...
Breaking Biology Technology: