Functions of human bitter taste receptors depend on N-glycosylation.
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. Non-glycosylated 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 non-glycosylated hTAS2R16 partially, we conclude that glycosylation is important for receptor maturation but not for its function per se.
Reichling
Claudia
C
Department Molecular Genetics, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
Meyerhof
Wolfgang
W
Behrens
Maik
M
D002460:Cell Line; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000502:physiology; D013649:Taste / Q000187:drug effects / Q000502:physiology*; D013650:Taste Buds / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D013652:Taste Threshold / Q000187:drug effects / Q000502:physiology; D014415:Tunicamycin / Q000494:pharmacology; D000098706:Taste Receptors, Type 2
D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; D014415:Tunicamycin