Humans can detect and distinguish the five basic taste qualities salty, sour, sweet, umami, and bitter (1). Gustatory stimuli are detected by taste receptor cells, which are organized in groups of 60 -100 cells forming a taste bud. One to multiple taste buds are embedded within morphologically different types of taste papillae distributed over the tongue surface. Each taste bud exhibits a single apical porus exposing the microvilli of the receptor cells to the oral cavity (2).The human TAS2R gene family of bitter receptors belongs to the G protein-coupled receptor superfamily and consists of ϳ25 members (3). The identification of activating bitter compounds for

Human bitter taste receptors of the TAS2R gene family play a crucial role as warning sensors against the ingestion of toxic food compounds. Moreover, the genetically highly polymorphic hTAS2Rs recognize an enormous number of structurally diverse toxic and non-toxic bitter substances, and hence, may substantially influence our individual eating habits. Heterologous expression in mammalian cells is a useful tool to investigate interactions between these receptors and their agonists. However, many bitter taste receptors are poorly expressed at the cell surface of heterologous cells requiring the addition of plasma membrane export promoting epitopes to the native receptor proteins. Currently, nothing is known about amino acid motifs or other receptor-intrinsic features of TAS2Rs affecting plasma membrane association. In the present study, we analyzed the Asn-linked glycosylation of hTAS2Rs at a consensus sequence in the second extracellular loop, which is conserved among all 25 hTAS2Rs. Nonglycosylated receptors exhibit substantially lower cell surface localization and reduced association with the cellular chaperone calnexin. As the auxiliary factors receptor transporting proteins 3 and 4 are able to restore the function of nonglycosylated hTAS2R16 partially, we conclude that glycosylation is important for receptor maturation but not for its function per se.

The molecular basis of human bitter taste perception is an area of intense research. Only 25 G protein-coupled receptors belonging to the hTAS2R gene family face the challenge to detect thousands of structurally different bitter compounds, most of which are plant metabolites. Since many natural bitter compounds are highly toxic, whereas others are part of our daily diets, bitter taste was crucial during evolution and still most likely affects our food selection. The article presented here addresses biosynthesis, functional analyses of TAS2Rs and TAS2R variants, as well as gustatory expression of hTAS2R genes.