| 1. |
Sanematsu K, Yamamoto M, Nagasato Y, Kawabata Y, Watanabe Y, Iwata S, Takai S, Toko K, Matsui T, Wada N, Shigemura N., Prediction of dynamic allostery for the transmembrane domain of the sweet taste receptor subunit, TAS1R3, Commun Biol., 10.1038/s42003-023-04705-5., 6(1), 340, 2023.04. |
| 2. |
Oike A, Iwata S, Hirayama A, Ono Y, Nagasato Y, Kawabata Y, Takai S, Sanematsu K, Wada N, Shigemura N., Bisphosphonate affects the behavioral responses to HCl by disrupting farnesyl diphosphate synthase in mouse taste bud and tongue epithelial cells , Sci Rep., 10.1038/s41598-022-25755-5, 12(1), 21246, 2022.12. |
| 3. |
Serrano J, Seflova J, Park J, Pribadi M, Sanematsu K, Shigemura N, Serna V, Yi F, Mari A, Procko E, Pratley RE, Robia SL, Kyriazis GA., The Ile191Val is a partial loss-of-function variant of the TAS1R2 sweet-taste receptor and is associated with reduced glucose excursions in humans. , Mol Metab. , 10.1016/j.molmet.2021.101339. , 54, 101339., 2021.09. |
| 4. |
Yamada Y, Takai S, Watanabe Y, Osaki A, Kawabata Y, Oike A, Hirayama A, Iwata S, Sanematsu K, Tabata S, Shigemura N., Gene expression profiling of α-gustducin-expressing taste cells in mouse fungiform and circumvallate papillae, Biochem Biophys Res Commun., 10.1016/j.bbrc.2021.04.022, 557, 206-212, 2021.04. |
| 5. |
Fumie Hirose, Shingo Takai, Ichiro Takahashi, Noriatsu Shigemura, Expression of protocadherin-20 in mouse taste buds, Scientific reports, 10.1038/s41598-020-58991-8, 10, 1, 2020.12, Taste information is detected by taste cells and then transmitted to the brain through the taste nerve fibers. According to our previous data, there may be specific coding of taste quality between taste cells and nerve fibers. However, the molecular mechanisms underlying this coding specificity remain unclear. The purpose of this study was to identify candidate molecules that may regulate the specific coding. GeneChip analysis of mRNA isolated from the mice taste papillae and taste ganglia revealed that 14 members of the cadherin superfamily, which are important regulators of synapse formation and plasticity, were expressed in both tissues. Among them, protocadherin-20 (Pcdh20) was highly expressed in a subset of taste bud cells, and co-expressed with taste receptor type 1 member 3 (T1R3, a marker of sweet- or umami-sensitive taste cells) but not gustducin or carbonic anhydrase-4 (markers of bitter/sweet- and sour-sensitive taste cells, respectively) in circumvallate papillae. Furthermore, Pcdh20 expression in taste cells occurred later than T1R3 expression during the morphogenesis of taste papillae. Thus, Pcdh20 may be involved in taste quality-specific connections between differentiated taste cells and their partner neurons, thereby acting as a molecular tag for the coding of sweet and/or umami taste.. |
| 6. |
Osaki A, Sanematsu K, Yamazoe J, Hirose F, Watanabe Y, Kawabata Y, Oike A, Hirayama A, Yamada Y, Iwata S, Takai S, Wada N, Shigemura N, Drinking Ice-cold Water Reduces the Severity of Anticancer Drug-induced Taste Dysfunction in Mice, Int J Mol Sci., 10.3390/ijms21238958, 21, (23), 8958, 2020.11, Taste disorders are common adverse effects of cancer chemotherapy that can reduce quality of life and impair nutritional status. However, the molecular mechanisms underlying chemotherapy-induced taste disorders remain largely unknown. Furthermore, there are no effective preventive measures for chemotherapy-induced taste disorders. We investigated the effects of a combination of three anticancer drugs (TPF: docetaxel, cisplatin and 5-fluorouracil) on the structure and function of mouse taste tissues and examined whether the drinking of ice-cold water after TPF administration would attenuate these effects. TPF administration significantly increased the number of cells expressing apoptotic and proliferative markers. Furthermore, TPF administration significantly reduced the number of cells expressing taste cell markers and the magnitudes of the responses of taste nerves to tastants. The above results suggest that anticancer drug-induced taste dysfunction may be due to a reduction in the number of taste cells expressing taste-related molecules. The suppressive effects of TPF on taste cell marker expression and taste perception were reduced by the drinking of ice-cold water. We speculate that oral cryotherapy with an ice cube might be useful for prophylaxis against anticancer drug-induced taste disorders in humans.. |
| 7. |
Shigemura N, Takai S, Hirose F, Yoshida R, Sanematsu K, Ninomiya Y., Expression of Renin-Angiotensin System Components in the Taste Organ of Mice, Nutrients., 10.3390/nu11092251, 11, 9, 11(9). pii: E2251, 2019.09. |
| 8. |
Jihye Park, Balaji Selvam, Keisuke Sanematsu, Noriatsu Shigemura, Diwakar Shukla, Erik Procko, Structural architecture of a dimeric class C GPCR based on co-trafficking of sweet taste receptor subunits, Journal of Biological Chemistry, 10.1074/jbc.RA118.006173, 294, 13, 4759-4774, 2019.03, Class C G protein– coupled receptors (GPCRs) are obligatory dimers that are particularly important for neuronal responses to endogenous and environmental stimuli. Ligand recognition through large extracellular domains leads to the reorganization of transmembrane regions to activate G protein signaling. Although structures of individual domains are known, the complete architecture of a class C GPCR and the mechanism of interdomain coupling during receptor activation are unclear. By screening a mutagenesis library of the human class C sweet taste receptor subunit T1R2, we enhanced surface expression and identified a dibasic intracellular retention motif that modulates surface expression and co-trafficking with its heterodimeric partner T1R3. Using a highly expressed T1R2 variant, dimerization sites along the entire subunit within all the structural domains were identified by a comprehensive mutational scan for co-trafficking with T1R3 in human cells. The data further reveal that the C terminus of the extracellular cysteine-rich domain needs to be properly folded for T1R3 dimerization and co-trafficking, but not for surface expression of T1R2 alone. These results guided the modeling of the T1R2–T1R3 dimer in living cells, which predicts a twisted arrangement of domains around the central axis, and a continuous folded structure between transmembrane domain loops and the cysteine-rich domains. These insights have implications for how conformational changes between domains are coupled within class C GPCRs.. |
| 9. |
Shingo Takai, Yu Watanabe, Keisuke Sanematsu, Ryusuke Yoshida, Robert F. Margolskee, Peihua Jiang, Ikiru Atsuta, Kiyoshi Koyano, Yuzo Ninomiya, Noriatsu Shigemura, Effects of insulin signaling on mouse taste cell proliferation, PloS one, 10.1371/journal.pone.0225190, 14, 11, 2019.01, Expression of insulin and its receptor (IR) in rodent taste cells has been proposed, but exactly which types of taste cells express IR and the function of insulin signaling in taste organ have yet to be determined. In this study, we analyzed expression of IR mRNA and protein in mouse taste bud cells in vivo and explored its function ex vivo in organoids, using RT-PCR, immunohistochemistry, and quantitative PCR. In mouse taste tissue, IR was expressed broadly in taste buds, including in type II and III taste cells. With using 3-D taste bud organoids, we found insulin in the culture medium significantly decreased the number of taste cell and mRNA expression levels of many taste cell genes, including nucleoside triphosphate diphosphohydrolase-2 (NTPDase2), Tas1R3 (T1R3), gustducin, carbonic anhydrase 4 (CA4), glucose transporter-8 (GLUT8), and sodium-glucose cotransporter-1 (SGLT1) in a concentration-dependent manner. Rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR) signaling, diminished insulin’s effects and increase taste cell generation. Altogether, circulating insulin might be an important regulator of taste cell growth and/or proliferation via activation of the mTOR pathway.. |
| 10. |
Noriatsu Shigemura, Yuzo Ninomiya, Recent Advances in Molecular Mechanisms of Taste Signaling and Modifying., Int Rev Cell Mol Biol., 323, 71-106, 2016.02. |
| 11. |
Noriatsu Shigemura, Modulation of Taste Responsiveness by Angiotensin II., Food Science and Technology Research, 21 , 6, 757-764, 2015.06. |
| 12. |
Noriatsu Shigemura, Angiotensin II and taste sensitivity., Japanese Dental Science Review, 51, 2, 51-8, 2015.05. |
| 13. |
Noriatsu Shigemura, Shusuke Iwata, Keiko Yasumatsu, Tadahiro Ohkuri, Nao Horio, Keisuke Sanematsu, Ryusuke Yoshida, Robert F Margolskee, Yuzo Ninomiya, Angiotensin II modulates salty and sweet taste sensitivities., J Neurosci., 33, 15, 6267-6277, 2013.04, アンジオテンシンIIは、視床下部、副腎や血管などに発現するAT1受容体を介して、血圧や体内Na+濃度を調節する鍵ホルモンとして知られている。我々は、このアンジオテンシンIIが末梢の味覚器にも働き、塩味感受性を低下させ NaCl溶液の摂取量を増加させること、さらに甘味感受性を増強することで糖分摂取にも影響することを明らかにした。この“味覚を介したNa+/糖ホメオスタシス維持機構”のさらなる解明は、高血圧や肥満・糖尿病などの生活習慣病に対する新たな予防・治療法の開発”に繋がることが期待される。. |
| 14. |
Shigemura N, Shirosaki S, Ohkuri T, Sanematsu K, Islam AA, Ogiwara Y, Kawai M, Yoshida R, Ninomiya Y., Variation in umami perception and in candidate genes for the umami receptor in mice and humans.
, Am J Clin Nutr. , 90(3):764S-769S., 2009.09. |
| 15. |
Shigemura N, Shirosaki S, Sanematsu K, Yoshida R, Ninomiya Y., Genetic and molecular basis of individual differences in human umami taste perception., PLoS One., 4(8):e6717., 2009.08. |
| 16. |
Nakagawa Y, Nagasawa M, Yamada S, Hara A, Mogami H, Nikolaev VO, Lohse MJ, Shigemura N, Ninomiya Y, Kojima I., Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion., PLoS One., 4(4):e5106, 2009.04. |
| 17. |
Nakamura Y, Sanematsu K, Ohta R, Shirosaki S, Koyano K, Nonaka K, Shigemura N, Ninomiya Y., Diurnal variation of human sweet taste recognition thresholds is correlated with plasma leptin levels., Diabetes. , 57(10):2661-5., 2008.10. |
| 18. |
Shigemura, N., Nakao, K., Yasuo, T., Murata, Y., Yasumatsu, K., Nakashima, A., Katsukawa, H., Sako, N., Ninomiya, Y. , Gurmarin sensitivity of sweet taste responses is associated with co-expression patterns of T1r2, T1r3, and gustducin. , Biochem. Biophys. Res. Commun., 367, 356-363 , 2008.03. |
| 19. |
Shigemura, N., Ohkuri, T., Sadamitsu, C., Yasumatsu, K., Yoshida, R., Beauchamp, G.K., Bachmanov, A.A., Ninomiya, Y. , Amiloride-sensitive NaCl taste responses are associated with genetic variation of ENaC α subunit in mice., Am. J. Physiol. Regul Integr. Comp. Physiol., 294, R66-R75 , 2008.01. |
| 20. |
Talavera K, Yasumatsu K, Voet T, Droogmans G, Shigemura N, Ninomiya Y, Margolskee RF, Nilius B., Heat-activation of the taste channel TRPM5 underlies thermal sensitivity to sweet., Nature, 438(7070):1022-5, 2005.12. |
| 21. |
Shigemura N, Islam AA, Sadamitsu C, Yoshida R, Yasumatsu K, Ninomiya Y., Expression of amiloride-sensitive epithelial sodium channels in mouse taste cells after chorda tympani nerve crush., Chemical Senses, 10.1093/chemse/bji046, 30, 6, 531-538, 30(6):531-8, 2005.07. |
| 22. |
Shigemura, N., Yasumatsu, K., Yoshida, R., Sako, N., Katsukawa, H., Nakashima K., Imoto, T., Ninomiya, Y., The role of the dpa locus in mice. Jan;30 (2005), Chemical Senses, 10.1093/chemse/bjh125, 30, I84-i85, Suppl 1:i84-i85, 2005.01. |
| 23. |
Shigemura N, Ohta R, Kusakabe Y, Miura H, Hino A, Koyano K, Nakashima K, Ninomiya Y., Leptin modulates behavioral responses to sweet substances by influencing peripheral taste structures., Endocrinology, 10.1210/en.2003-0602, 145, 2, 839-847, 2003.10. |
| 24. |
Shigemura N, Miura H, Kusakabe Y, Hino A, Ninomiya Y., Expression of leptin receptor (Ob-R) isoforms and signal transducers and activators of transcription (STATs) mRNAs in the mouse taste buds., Arch Histol Cytol., 10.1679/aohc.66.253, 66, 3, 253-260, 66(3):253-60., 2003.08. |
| 25. |
Ninomiya, Y., Shigemura, N., Yasumatsu, K., Ohta, R., Sugimoto, K., Nakashima, K. and Lindemann, B., Leptin and sweet taste., Vitam. Horm., 10.1016/S0083-6729(02)64007-5, 64, 221-248, 64: 221-247, 2002.05. |
