If TR1 and TR2 truly function in taste discrimination, their distribution should match in some way the distribution of different types of papillae, the researchers reasoned. Indeed, the team found that TR1 is expressed in nearly all fungiform taste buds, but is rare in taste buds of the bitter-sensitive circumvallate papillae. TR2 has the opposite distributionit is rarely expressed in fungiform papillae but is expressed in all circumvallate papillae. Both TR1 and TR2 are expressed in foliate taste buds, but usually not in the same cell of a given taste bud.
That was encouraging, but still not enough to certify TR1 and TR2 as taste receptors. The next critical step was to find out exactly where their proteins are found in the receptor cells that make up taste buds.
Like sensory cells in the visual and olfactory systems, taste receptor cells have specialized compartments that function something like the lobbies of busy office buildings: They receive stimuli from the outside world and then translate those stimuli into signals, which are sent on to the brain for interpretation. In a taste receptor cell, this bustling lobby is the taste pore. It is here, researchers believe, that molecules of sweet, sour, salty and bitter stuff link up with receptors, and the real work of taste recognition begins.
Using the office building analogy, taste receptors are like the security guards who ask visitors for identification and then send them to the appropriate floor. If TR1 and TR2 are bona fide taste receptors, you would expect to find them stationed at their posts in the taste pores. Using antibody labeling techniques that can pinpoint the location of specific molecules, that's just what Zuker and his colleagues found. TR1 turned up only in the taste pore region of foliate and fungiform taste buds; TR2 was in the taste pores of circumvallate and foliate taste buds.
Zuker cautions that the evidence implicating TR1 and TR2 is, so far, only "guilt by association." The two proteins resemble other receptors, and they're found where you'd expect receptors to be, but more experiments are needed to show that they actually do function as taste receptors. One key experiment would be to show that they recognize, bind and are activated by molecules bearing the appropriate tastes. Another important study would be to generate "knockout" mice that lack TR1 or TR2 and see if these mice are incapable of making certain taste distinctions. Both types of studies are under way in the Zuker and Ryba labs.