Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor

Abstract

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...

Involvement of the Calcium-sensing Receptor in Human Taste Perception

“…It has been previously shown that the sweet receptor is a heterodimer of T1R2 and T1R3 (17,18), that the umami receptor is a heterodimer of T1R1 and T1R3 (17,19), and that the bitter receptors are a family of T2R receptors (20,21). The epithelial sodium channel (22) and transient receptor potential family members PKD1L3 and PKD2L1 (23) are plausible candidates as receptors for the salty and sour (acid) tastes, respectively. A common characteristic of kokumi taste substances such as GSH is that they are tasteless by themselves but enhance basic tastes.…”

A polycystin-1 controls postcopulatory reproductive selection in mice

“…Functional studies indicate that polycystin-1 proteins are components of mechanosensory or chemosensory signal transduction mechanisms (4,5). In the renal tubule epithelium Pkd1 is located in the primary cilium and acts as a fluid flow sensor (6,7), whereas Pkd1l3 is associated with sour taste transduction (8,9). In contrast, the functions of other family members are poorly understood.…”

A Quantitative Analysis of the Spatiotemporal Pattern of Transient Receptor Potential Gene Expression in the Developing Mouse Cochlea

“…PKD1L3 and TRPP3 (PKD2L1) have been shown to form heteromeric channels in sensory taste receptor cells and may contribute to sour taste transduction (Ishimaru et al 2006). It is attractive to speculate that the parallel rise in expression that we note here may indicate an interaction between PKD1L3 and TRPP3 in the cochlea that gives rise to physiologically significant aspects of cochlear function.…”