Taste buds are multicellular sensors reporting taste, which reflects quality and potential toxicity for potential food items. Two of the 3 cell types (Type II and Type III) comprising a taste bud are well described in terms of molecular features for transduction and transmission of different taste qualities whereas Type I cells are described as being supporting or glial-like. In this proposal we test the hypothesis that Type I taste cells serve two critical functions. First, our preliminary reconstructions of taste buds show that Type I cells completely surround and separate other cell types in a taste bud; thus Type I cells must be important for signaling and integration of taste information within the bud. Second, our ultrastructural analysis further shows that some Type I cells extend an apical process through the taste pore to sample the oral contents and so may transduce some components of salty taste. We propose to use correlated anatomical, functional and molecular means to classify and characterize Type I cells in taste buds from mice. The first set of experiments will extend our preliminary analysis of Type I cells in circumvallate taste buds to test whether Type I cells in fungiform taste buds similarly separate Type II and Type III cells from one another. Further we test whether the Type I cells participate in intrabud signaling by releasing GABA or other neurotransmitters in response to the ATP released by stimulated Type II (sweet-bitter-umami) cells. The GABA can then act on adjacent Type II cells to terminate signaling and reduce subsequent responsiveness to tastants.
In Aim 2, we test whether any morphological subtype of Type I cells expresses functional amiloride-sensitive salt (ENaC) receptors and if so, determine the relationship of these cells to sensory nerve fibers. Conventional EM indicates that Type I cells do not form synapses leaving open the question of how any Type I cell response could be communicated to the nervous system. We suggest that Type I cells, like glial cells in the CNS, can release neurotransmitter by reversal of membrane transporters for GABA or glutamate or opening of large pore channels. In the end we will have resolved two important questions in transduction and transmission of taste information by defining the nature of intrabud signaling between receptor cell types, and secondly finally determining the identity of cells underlying amiloride-sensitive salt transduction.
The function of the gustatory system is to discriminate nutritious substances from substances that are toxic or harmful to the body. Understanding the molecular events underlying detection and transmission of taste information may lead to the development of pharmaceutical agents that can modulate food intake, a major factor in controlling obesity. The proposed studies examine crosstalk between cells in the taste bud and how some salty tastes are detected.
