title: Intracellular acidification is required for full activation of the sweet taste receptor by miraculin.
abstract: Acidification of the glycoprotein, miraculin (MCL), induces sweet taste in humans, but not in mice. The sweet taste induced by MCL is more intense when acidification occurs with weak acids as opposed to strong acids. MCL interacts with the human sweet receptor subunit hTAS1R2, but the mechanisms by which the acidification of MCL activates the sweet taste receptor remain largely unexplored. The work reported here speaks directly to this activation by utilizing a sweet receptor TAS1R2 + TAS1R3 assay. In accordance with previous data, MCL-applied cells displayed a pH dependence with citric acid (weak acid) being right shifted to that with hydrochloric acid (strong acid). When histidine residues in both the intracellular and extracellular region of hTAS1R2 were exchanged for alanine, taste-modifying effect of MCL was reduced or abolished. Stronger intracellular acidification of HEK293 cells was induced by citric acid than by HCl and taste-modifying effect of MCL was proportional to intracellular pH regardless of types of acids. These results suggest that intracellular acidity is required for full activation of the sweet taste receptor by MCL.
authors.affiliation: Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sanematsu
authors.affiliation: Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kitagawa
authors.affiliation: Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.|OBT Research Center, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Yoshida
authors.affiliation: Japan International Research Center for Agricultural Sciences, 1-1 Ohwashi, Tsukuba, Ibaraki 305-8686, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Nirasawa
authors.affiliation: Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Noriatsu
authors.initials: N
authors.lastname: Shigemura
authors.affiliation: Section of Oral Neuroscience, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.|Division of Sensory Physiology, Research and Development Center for Taste and Odor sensing, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Ninomiya
mesh_terms: D000818:Animals; D019343:Citric Acid; D006023:Glycoproteins / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D006851:Hydrochloric Acid; D006863:Hydrogen-Ion Concentration; D051379:Mice; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D013549:Sweetening Agents; D013649:Taste
chemical_list: D006023:Glycoproteins; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; D013549:Sweetening Agents; C008533:miraculin protein, Synsepalum dulcificum; C431926:taste receptors, type 1; D019343:Citric Acid; D006851:Hydrochloric Acid