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Release: Oct. 25, 2000

UI researchers identify protein involved in mammals' sense of touch

IOWA CITY, Iowa -- Of all the senses, touch is the least understood at the molecular level. Sensory receptors in the skin transmit a wealth of information about our environment. However, the receptors that respond to mechanical stimulation in mammals have remained unknown.

Now, University of Iowa researchers and their colleagues at the Max-Delbruck-Center (MDC) for Molecular Medicine in Berlin, Germany, have made a discovery that is the first step in understanding the molecular basis for this process. The findings appear in the Oct. 26 issue of the journal Nature.

"This work identified one of the molecular components that may form a sensory receptor for light touch in mammals," said Maggie P. Price, Ph.D., UI assistant research scientist in internal medicine and lead author of the study.

The researchers have identified a protein that plays a role in the perception of light touch in mice. The protein was discovered because of its similarity to a protein thought to mediate the sense of touch in a small worm, C. elegans. Researchers often use this worm to search for interesting genes. By looking at genetic mutations, which disrupted the worms' sense of touch, other researchers identified genes postulated to be involved in touch sensation.

"We used the information about those C. elegans genes to help us identify proteins in mice that might have a similar function," Price said.

The protein they found is called brain sodium channel 1 (BNC1). As the name suggests, it was initially found in the brain. However, they soon found that BNC1 was also present in sensory nerves. These cells send out long nerve fibers that end just below the skin. The team showed that the protein is present at the very tips of the nerve endings.

To test the function of the BNC1 protein, the researchers generated genetically modified mice that could not make the protein. The mice could still perceive touch, indicating that this protein was not necessary for all forms of touch perception. In collaboration with Gary R. Lewin, Ph.D., independent group leader at MDC in Berlin and another author of this study, individual nerve fibers were examined. Strikingly, mice missing the protein showed a very specific and selective deficit in one type of touch perception; rapidly adapting mechanoreceptors were much less sensitive. These fibers sense very light touch.

"The BNC1 protein is an ion channel located at the tips of nerves surrounding hair follicles. When the hair moves, the channels open and the flow of ions causes an electrical signal to be sent through the long nerve fiber to the spinal cord and from there on to the brain," Price explained.

As a result, the brain gets the message that the hair has moved. The UI researchers believe that BNC1 may be a major component of this type of touch receptor complex.

So far the UI researchers have shown that this protein is involved in gentle touch perception but Price is excited about future studies. Given the protein's appearance in many places in the body, Price expects the team will discover that BNC1 and related proteins play many roles in sensory perception.

"These proteins clearly work as parts of large multi-protein complexes. The thought is that different combinations of these proteins probably have different functions in sensory detection," Price said. "We are interested in these proteins because they are likely to be involved in many different processes such as touch sensation, pain perception and taste, to mention a few."

Scientists have so far identified nine mammalian genes in the protein family. In fruit flies and C. elegans, two organisms whose genomes have been fully sequenced, many more of these ion channel genes have been identified.

Now that the UI team has identified one protein component of a touch receptor, they will be able to use a host of experiments to identify other protein parts of the receptor complexes.

"This work provides an important first step toward understanding the elusive sense of touch. It may also pave the way to elucidating 'senses' of which we are not consciously aware such as the stretch of blood vessels that control blood pressure," said Michael J. Welsh, M.D., principal investigator of the study. Welsh is a Howard Hughes Medical Institute (HHMI) investigator and Roy J. Carver Professor of Internal Medicine and Physiology and Biophysics at the UI.

The study was supported by the HHMI.

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