title: Comprehensive Analysis of Mouse Bitter Taste Receptors Reveals Different Molecular Receptive Ranges for Orthologous Receptors in Mice and Humans.
abstract: One key to animal survival is the detection and avoidance of potentially harmful compounds by their bitter taste. Variable numbers of taste 2 receptor genes expressed in the gustatory end organs enable bony vertebrates (Euteleostomi) to recognize numerous bitter chemicals. It is believed that the receptive ranges of bitter taste receptor repertoires match the profiles of bitter chemicals that the species encounter in their diets. Human and mouse genomes contain pairs of orthologous bitter receptor genes that have been conserved throughout evolution. Moreover, expansions in both lineages generated species-specific sets of bitter taste receptor genes. It is assumed that the orthologous bitter taste receptor genes mediate the recognition of bitter toxins relevant for both species, whereas the lineage-specific receptors enable the detection of substances differently encountered by mice and humans. By challenging 34 mouse bitter taste receptors with 128 prototypical bitter substances in a heterologous expression system, we identified cognate compounds for 21 receptors, 19 of which were previously orphan receptors. We have demonstrated that mouse taste 2 receptors, like their human counterparts, vary greatly in their breadth of tuning, ranging from very broadly to extremely narrowly tuned receptors. However, when compared with humans, mice possess fewer broadly tuned receptors and an elevated number of narrowly tuned receptors, supporting the idea that a large receptor repertoire is the basis for the evolution of specialized receptors. Moreover, we have demonstrated that sequence-orthologous bitter taste receptors have distinct agonist profiles. Species-specific gene expansions have enabled further diversification of bitter substance recognition spectra.
authors.affiliation: From the Department of Molecular Genetics, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Lossow
authors.affiliation: From the Department of Molecular Genetics, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hübner
authors.affiliation: From the Department of Molecular Genetics, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Natacha
authors.initials: N
authors.lastname: Roudnitzky
authors.affiliation: the Givaudan Flavors Corporation, Cincinnati, Ohio 45216, and.
authors.forename: Jay P
authors.initials: JP
authors.lastname: Slack
authors.affiliation: the Department of Drug Sciences, University of Eastern Piemonte, 28100 Novara, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Pollastro
authors.affiliation: From the Department of Molecular Genetics, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany, behrens@dife.de.
authors.forename: Maik
authors.initials: M
authors.lastname: Behrens
authors.affiliation: From the Department of Molecular Genetics, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Meyerhof
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D006801:Humans; D051379:Mice; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity
chemical_list: D043562:Receptors, G-Protein-Coupled
keywords: G protein-coupled receptor (GPCR); bitter taste receptor; calcium imaging; cell signaling; heterologous expression; human; mouse