Animals use their gustatory systems to evaluate the nutritious value, toxicity, sodium content, and acidity of food. Although characterization of molecular identities that receive taste chemicals is essential, molecular receptors underlying sour taste sensation remain unclear. Here, we show that two transient receptor potential (TRP) channel members, PKD1L3 and PKD2L1, are coexpressed in a subset of taste receptor cells in specific taste areas. Cells expressing these molecules are distinct from taste cells having receptors for bitter, sweet, or umami tastants. The PKD2L1 proteins are accumulated at the taste pore region, where taste chemicals are detected. PKD1L3 and PKD2L1 proteins can interact with each other, and coexpression of the PKD1L3 and PKD2L1 is necessary for their functional cell surface expression. Finally, PKD1L3 and PKD2L1 are activated by various acids when coexpressed in heterologous cells but not by other classes of tastants. These results suggest that PKD1L3 and PKD2L1 heteromers may function as sour taste receptors.chemical senses ͉ polycystic kidney disease ͉ gustation ͉ ion channel ͉ acid T aste reception occurs at the apical tip of taste cells that form taste buds. Each taste bud has an onion-like shape and is composed of 50-100 taste cells that possess microvilli (1). There are four major taste areas in the oral region in which taste buds are concentrated: three taste areas on the tongue (circumvallate papilla, foliate papilla, and fungiform papilla) and a fourth taste area on the palate on the top surface of the mouth. In mammals, taste is generally classified into five distinct taste modalities: bitter, sweet, umami (the taste of some L-amino acids), salty, and sour (1). Much progress has been made in unraveling the molecular mechanisms of bitter, sweet, and umami taste in recent years (2-5). Bitter chemicals are detected by Ϸ30 T2R receptor family members. Sugars and sweeteners are detected by T1R2 and T1R3 heteromers, whereas umami tasting L-amino acids are detected by T1R1 and T1R3.In contrast, the molecular mechanisms involved in sensing salty and sour taste are poorly understood and even confusing (6). Regarding sour taste transduction, several candidate receptors have been proposed. For example, acid-sensing ion channel (ASIC)2 is proposed to function as a sour receptor in the rat (7). However, it is not expressed in mouse taste cells and not required for acid sensation (8). HCN1 and HCN4, members of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, also are putative sour receptor channels (9). However, calcium imaging experiments using taste bud slices did not support this possibility, because Cs ϩ , an inhibitor of HCN channels, did not block Ca 2ϩ response of taste cells to acid stimuli (10). In addition, the proteins are localized on basolateral membranes of taste cells. Members of two pore domain K ϩ channels also are proposed to have some roles in acid transduction (11,12). However, their expression levels seem to be low, and the proteins are mainly distrib...

Recent progress in the molecular biology of taste reception has revealed that in mammals, the heteromeric receptors T1R1/3 and T1R2/3 respond to amino acids and sweeteners, respectively, whereas T2Rs are receptors for bitter tastants. Similar taste receptors have also been characterized in fish, but their ligands have not been identified yet. In the present study, we conducted a series of experiments to identify the fish taste receptor ligands. Facial nerve recordings in zebrafish (Danio rerio) demonstrated that the fish perceived amino acids and even denatonium, which is a representative of aversive bitter compounds for mammals and Drosophila. Calcium imaging analysis of T1Rs in zebrafish and medaka fish (Oryzias latipes) using an HEK293T heterologous expression system revealed that both T1R1/3 and a series of T1R2/3 responded to amino acids but not to sugars. A triple-labeling, in situ hybridization analysis demonstrated that cells expressing T1R1/3 and T1R2/3s exist in PLC␤2-expressing taste bud cells of medaka fish. Functional analysis using T2Rs showed that zfT2R5 and mfT2R1 responded to denatonium. Behavior observations confirmed that zebrafish prefer amino acids and avoid denatonium. These results suggest that, although there may be some fish-specific way of discriminating ligands, vertebrates could have a conserved gustatory mechanism by which T1Rs and T2Rs respond to attractive and aversive tastants, respectively.

The transient receptor potential channel, PKD2L1, is reported to be a candidate receptor for sour taste based on molecular biological and functional studies. Here, we investigated the expression pattern of PKD2L1-immunoreactivity (IR) in taste buds of the mouse. PKD2L1-IR is present in a few elongate cells in each taste bud as reported previously. The PKD2L1-expressing cells are different from those expressing PLCbeta2, a marker of Type II cells. Likewise PKD2L1-immunoreactive taste cells do not express ecto-ATPase which marks Type I cells. The PKD2L1-positive cells are immunoreactive for neural cell adhesion molecule, serotonin, PGP-9.5 (ubiquitin carboxy-terminal transferase), and chromogranin A, all of which are present in Type III taste cells. At the ultrastructural level, PKD2L1-immunoreactive cells form synapses onto afferent nerve fibers, another feature of Type III taste cells. These results are consistent with the idea that different taste cells in each taste bud perform distinct functions. We suggest that Type III cells are necessary for transduction and/or transmission of information about "sour", but have little or no role in transmission of taste information of other taste qualities.