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NIH Researchers and UCSD Identify Candidate "Taste" Genes

May 1999

The National Institute on Deafness and Other Communication Disorders (NIDCD) collaborates with scientists at the National Institute on Dental and Craniofacial Research (NIDCR) and Howard Hughes Medical Institute researchers at the University of California, San Diego, to identify the genes likely responsible for the mammalian sense of taste.

In a recent issue of the scientific journal Cell, the researchers describe genes that encode two novel proteins expressed in cells specifically geared to the sense of taste. The proteins, members of a new group of "G protein" receptors, were singled out as a result of their unique expression in taste buds of the tongue and palate epithelium.

"Research on the mechanisms involved in mammalian taste receptors is full of promise," said NIDCD Director, Dr. James F. Battey, a co-author of the study. "In this collaborative effort, we are expanding knowledge about the molecular basis of taste perception." The isolation of the candidate taste receptor genes provides the groundwork necessary for manipulating the perception of taste and stimulating or blocking taste cell function. The discovery could one day hold implications for engineering foods to specific taste qualities. The identification also sets the stage for mapping how the sense of taste is "wired" from the mouth to the brain.

"These two molecules have the hallmarks we expect of taste receptors," said co- investigator Nicholas Ryba from the NIDCR. "They may be the key to unlocking our understanding of how we detect taste, which is unclear at the moment. We must now demonstrate that functionally they can do the job."

"The identity of the receptor molecules for the different sensory modalities, like vision, olfaction and taste, represents the Holy Grail of the sensory field," said UCSD's Charles Zuker, a co-author of the report. "These receptor molecules provide the unique specificity and selectivity of each sensory system. The color receptors in our retinas allow us to see in color, and the receptors in our nose endow us with great discrimination for smell. In the case of taste, they are what make sweet cells respond to sweet substances, bitter cells to bitter compounds, and so on."

"This paper is an exciting and important contribution to our understanding of the neurobiology of taste," said Dr. Lubert Stryer, professor of neurobiology at Stanford University and author of the most widely used college biochemistry textbook. "Dr. Zuker's and Ryba's group have isolated the genes for two transmembrane proteins that may well be the first taste receptors. They are specifically localized in a subset of taste neurons in the tongue-- and nowhere else--and are positioned in just the right place in these cells. These candidate taste receptors resemble the receptors that mediate sensory processes such as vision and olfaction. This work has opened new vistas in taste research."

The mechanism of taste in mammals begins with the taste buds on the tongue. Sweet receptors are mostly found on the tip of the tongue, sour receptors on the sides, salty on the tip and frontal sides, and bitter on the back of the tongue. Each taste bud contains roughly 50 to 150 taste receptor cells that act like tiny taste interpretation machines. Proteins on the surface of these cells bind to substances, recognize them, and switch the cells "on" by prompting them into an active state. The cells then transmit information to nerve cells that relay the data to the taste centers of the brain cortex.

"We began a systematic search for the molecular basis of taste several years ago and it is very gratifying to find receptors that seem to be involved in this process," said Dr. Mark Hoon of the NIDCR, first author of this study.

The research team used specialized DNA screening techniques to scan for candidate receptors in taste buds of rats and mice. The strategy succeeded in isolating two novel receptors, TR1 and TR2.

"The identification of candidate mammalian taste receptors makes it possible to understand how the taste cells differ from one another and how taste information is encoded so that the brain can interpret and respond to taste stimuli on the tongue," said Zuker, a professor of biology and neurosciences at UCSD.

Using this new information and biological screening techniques, millions of molecules could be evaluated to find out which substances bind to which specific taste receptor. A molecule that binds and activates a sweet receptor, Zuker and Ryba say, is likely to be perceived as sweet.

"It doesn't matter if it looks like a sweet molecule or behaves like a sweet molecule, if it binds and activates the sweet receptor, it will be sweet," Zuker added. " That is what the sense of taste is all about."

In addition to Drs. Battey, Zuker, Ryba and Hoon, the research team included Drs. Elliot Adler and Jürgen Lindemeier, Howard Hughes Medical Institute researchers at UCSD. The research was also partly supported by NIDCD.

May 1999

Used with permission from UCSD.
For more information contact:
Cheryl Fells, NIDCD at (301) 496-7243
fellsc@ms.nidcd.nih.gov
or Mario Aguilera, UCSD at (619) 534-7572

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