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NIDCD-funded Teams Find Cells, Receptors for Sour Taste

Your ability to taste the tart and tangy bite of a green apple is made possible by specially tasked "sour" taste cells located in taste buds throughout the tongue, says a team of scientists led by Charles S. Zuker, Ph.D., at the University of California, San Diego, and an investigator with the Howard Hughes Medical Institute, Chevy Chase, MD, who received partial funding from NIDCD, and Nicholas Ryba, Ph.D., of the National Institute of Dental and Craniofacial Research, one of the National Institutes of Health. In research published in the August 24 issue of Nature, the team of researchers has identified the cells and candidate receptor responsible for detecting sour taste. The ability to detect sour is the primary way that mammals distinguish spoiled and unripe foods. The same team had previously discovered the receptors and cells mediating sweet, bitter, and umami (savory) tastes.

Using bioinformatics—the study of biological information using computer and statistical analyses—and genetic studies, the San Diego researchers identified PKD2L1, as a candidate acid sensor. PKD2L1 is a member of the TRP family of ion channel receptors whose other members are also known to be involved in taste signal transduction. The team chose to study this protein as a possible receptor because it was not found in taste cells that express receptors for sweet, bitter, and umami, but instead was found in a previously unidentified population of taste cells. This was a prerequisite for their theory that each of the five basic tastes is mediated by distinct, non-overlapping classes of taste receptor cells. To test whether PKD2L1-expressing cells are indeed the mediators of sour taste, the researchers engineered a special strain of genetically altered mice lacking PKD2L1 cells and then tested the mice’s ability to detect the taste of sour. The mice were unable to detect sour, but they were able to continue to detect sweet, bitter, umami and salt, demonstrating that PKD2L1-expressing cells are the mammalian sour taste sensors.

In related work, another team of NIDCD-supported investigators led by Hiroaki Matsunami at Duke University in Durham, NC, also isolated the identical TRP channel receptors, which they describe as "sour-sensing" receptors. In addition to PKD2L1, the Duke University team isolated another protein, PKD1L3, and found that it too was specific to a certain population of taste cells that detect only sour taste. As was the case in the Nature study, the receptor cells were distinct from the taste cells for bitter, sweet, and umami. In research published in the August 15 issue of the Proceedings of the National Academy of Sciences, the Duke team confirmed that the receptors were localized to the taste pore, the site of interaction with sour substances. These receptors were specific for sour taste because they are activated by various acids and not by other types of taste compounds when expressed in tissue culture cells.

The discovery of sour receptors and their taste cells by these two research teams demonstrates that the detection of sour takes place in much the same way that sweet, bitter, and umami are detected—through separate taste-specific cells and their associated receptors. The finding helps refute a belief of some scientists that the detection of sour and salty tastes, which depend on the detection of ions, works differently than with the other tastes. Because the genetically engineered mice could detect salt, Zuker and his team conclude that salt-sensing cells must also function independently with their own receptors, which sets the stage for investigation into this last of the five basic tastes.

Interestingly, the San Diego investigators discovered that PKD2L1 is found in the nerve cells of the spinal cord, where sensing acidity might be important. According to the team, discovery of a sour receptor in the central nervous system could help explain how the body monitors the pH of critical body fluids and why defects in this mechanism may underlie a wide range of disorders.

The University of California, San Diego team also received postdoctoral support from the Deutsche Forschungsgemeinschaft (German Research Foundation) and the Human Frontiers Science program. The Duke University team also received postdoctoral support from the Japan Society for the Promotion of Science.