Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Keisuke Sanematsu Last modified date:2021.06.28

Lecturer / Oral Biological Sciences / Department of Dental Science / Faculty of Dental Science

1. 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..
2. Noriatsu Shigemura, Shingo Takai, Fumie Hirose, Ryusuke Yoshida, Keisuke Sanematsu, Yuzo Ninomiya, Expression of Renin-Angiotensin System Components in the Taste Organ of Mice, Nutrients, 10.3390/nu11092251, 11, 9, 2019.09, The systemic renin-angiotensin system (RAS) is an important regulator of body fluid and sodium homeostasis. Angiotensin II (AngII) is a key active product of the RAS. We previously revealed that circulating AngII suppresses amiloride-sensitive salt taste responses and enhances the responses to sweet compounds via the AngII type 1 receptor (AT1) expressed in taste cells. However, the molecular mechanisms underlying the modulation of taste function by AngII remain uncharacterized. Here we examined the expression of three RAS components, namely renin, angiotensinogen, and angiotensin-converting enzyme-1 (ACE1), in mouse taste tissues. We found that all three RAS components were present in the taste buds of fungiform and circumvallate papillae and co-expressed with αENaC (epithelial sodium channel α-subunit, a salt taste receptor) or T1R3 (taste receptor type 1 member 3, a sweet taste receptor component). Water-deprived mice exhibited significantly increased levels of renin expression in taste cells (p < 0.05). These results indicate the existence of a local RAS in the taste organ and suggest that taste function may be regulated by both locally-produced and circulating AngII. Such integrated modulation of peripheral taste sensitivity by AngII may play an important role in sodium/calorie homeostasis..
3. 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, 2019.01, 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..
4. Keisuke Sanematsu, Yuki Nakamura, Masatoshi Nomura, Noriatsu Shigemura, Yuzo Ninomiya, Diurnal variation of sweet taste recognition thresholds is absent in overweight and obese humans, Nutrients, 10.3390/nu10030297, 10, 3, 2018.03, Sweet taste thresholds are positively related to plasma leptin levels in normal weight humans: both show parallel diurnal variations and associations with postprandial glucose and insulin rises. Here, we tested whether this relationship also exists in overweight and obese (OW/Ob) individuals with hyperleptinemia. We tested 36 Japanese OW/Ob subjects (body mass index (BMI) > 25 kg/m2 ) for recognition thresholds for various taste stimuli at seven different time points from 8:00 a.m. to 10:00 p.m. using the staircase methodology, and measured plasma leptin, insulin, and blood glucose levels before each taste threshold measurement. We also used the homeostatic model assessment of insulin resistance (HOMA-IR) to evaluate insulin resistance. The results demonstrated that, unlike normal weight subjects, OW/Ob subjects showed no significant diurnal variations in the recognition thresholds for sweet stimuli but exhibited negative associations between the diurnal variations of both leptin and sweet recognition thresholds and the HOMA-IR scores. These findings suggest that in OW/Ob subjects, the basal leptin levels (~20 ng/mL) may already exceed leptin’s effective concentration for the modulation of sweet sensitivity and that this leptin resistance-based attenuation of the diurnal variations of the sweet taste recognition thresholds may also be indirectly linked to insulin resistance in OW/Ob subjects..
5. Ryusuke Yoshida, Shingo Takai, Keisuke Sanematsu, Robert F. Margolskee, Noriatsu Shigemura, Yuzo Ninomiya, Bitter Taste Responses of Gustducin-positive Taste Cells in Mouse Fungiform and Circumvallate Papillae, Neuroscience, 10.1016/j.neuroscience.2017.10.047, 369, 29-39, 2018.01, Bitter taste serves as an important signal for potentially poisonous compounds in foods to avoid their ingestion. Thousands of compounds are estimated to taste bitter and presumed to activate taste receptor cells expressing bitter taste receptors (Tas2rs) and coupled transduction components including gustducin, phospholipase Cβ2 (PLCβ2) and transient receptor potential channel M5 (TRPM5). Indeed, some gustducin-positive taste cells have been shown to respond to bitter compounds. However, there has been no systematic characterization of their response properties to multiple bitter compounds and the role of transduction molecules in these cells. In this study, we investigated bitter taste responses of gustducin-positive taste cells in situ in mouse fungiform (anterior tongue) and circumvallate (posterior tongue) papillae using transgenic mice expressing green fluorescent protein in gustducin-positive cells. The overall response profile of gustducin-positive taste cells to multiple bitter compounds (quinine, denatonium, cyclohexamide, caffeine, sucrose octaacetate, tetraethylammonium, phenylthiourea, L-phenylalanine, MgSO4, and high concentration of saccharin) was not significantly different between fungiform and circumvallate papillae. These bitter-sensitive taste cells were classified into several groups according to their responsiveness to multiple bitter compounds. Bitter responses of gustducin-positive taste cells were significantly suppressed by inhibitors of TRPM5 or PLCβ2. In contrast, several bitter inhibitors did not show any effect on bitter responses of taste cells. These results indicate that bitter-sensitive taste cells display heterogeneous responses and that TRPM5 and PLCβ2 are indispensable for eliciting bitter taste responses of gustducin-positive taste cells..
6. Keisuke Sanematsu, Noriatsu Shigemura, Yuzo Ninomiya, Binding properties between human sweet receptor and sweet-inhibitor, gymnemic acids, Journal of Oral Biosciences , 10.1016/j.job.2017.05.004 , 2017.05.
7. Jyotaki Masafumi, Keisuke Sanematsu, Noriatsu Shigemura, Ryusuke Yoshida, Yuzo Ninomiya, Leptin suppresses sweet taste responses of enteroendocrine STC-1 cells, Neuroscience, 10.1038/srep22807, 332, 76-87, 2016.09.
8. Keisuke Sanematsu, Masayuki Kitagawa, Ryusuke Yoshida, Satoru Nirasawa, Noriatsu Shigemura, Yuzo Ninomiya, Intracellular acidification is required for full activation of the sweet taste receptor by miraculin, Scientific reports, 10.1038/srep22807, 6, 22807, 2016.03.
9. Keisuke Sanematsu, Yuko Kusakabe, Noriatsu Shigemura, Takatsugu Hirokawa, Seiji Nakamura, Toshiaki Imoto, Yuzo Ninomiya, Molecular Mechanisms for Sweet-suppressing Effect of Gymnemic Acids, Journal of Biological Chemistry, M114.560409 [pii] 10.1074/jbc.M114.560409, 289, 37, 25711-25720, 2014.09.
10. Keisuke Sanematsu, Ryusuke Yoshida, Noriatsu Shigemura, Yuzo Ninomiya, Structure, function, and signaling of taste G-protein-coupled receptors, Current Pharmaceutical Biotechnology, 15, 10, 951-961, 2014.09.
11. Noriatsu Shigemura, Ryusuke Yoshida, Shusuke Iwata, Keisuke Sanematsu, Tadahiro Ohkuri, Nao Horio, Ryusuke Yoshida, Robert F. Margolskee, Yuzo Ninomiya, Angiotensin II Modulates Salty and Sweet Taste Sensitivities., J Neurosci., 33, 15, 6267-6277, 2013.04.
12. Ryusuke Yoshida, Mayu Niki, Masafumi Jotaki, Keisuke Sanematsu, Noriatsu Shigemura, Yuzo Ninomiya, Modulation of sweet responses of taste receptor cells., Semin Cell Dev Biol., 24, 3, 226-231, 2013.03.
13. Li YinJi, Akiko Kukita, Toshiyuki Watanabe, Toshio Takano, Pengfei Qu, Yuzo Ninomiya, Toshio Kukita, Nordihydroguaiaretic acid inhibition of NFATc1 suppresses osteoclastogenesis and arthritis bone
destruction in rats., Lab Invest., 92, 12, 1777-1787, 2012.12.
14. Horio N, Jyotaki M, Yoshida R, Sanematsu K, Shigemura N, Ninomiya Y., New frontiers in gut nutrient sensor research: nutrient sensors in the gastrointestinal tract: modulation of sweet taste sensitivity by leptin., J Pharmacol Sci., 112(1):8-12., 2010.01.
15. Yoshida R, Ohkuri T, Jyotaki M, Yasuo T, Horio N, Yasumatsu K, Sanematsu K, Shigemura N, Yamamoto T, Margolskee RF, Ninomiya Y., Endocannabinoids selectively enhance sweet taste., Proc Natl Acad Sci U S A., 12;107(2):935-9., 2010.01.
16. Yasumatsu K, Ohkuri T, Sanematsu K, Shigemura N, Katsukawa H, Sako N, Ninomiya Y., Genetically-increased taste cell population with G(alpha)-gustducin-coupled sweet receptors is associated with increase of gurmarin-sensitive taste nerve fibers in mice., BMC Neurosci., 10:152., 2009.12.
17. 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.
18. Genetic and molecular basis of individual differences in human umami taste perception., Shigemura N, Shirosaki S, Sanematsu K, Yoshida R, Ninomiya Y., PLoS One., 4(8):e6717., 2009.08.
19. Sanematsu K, Horio N, Murata Y, Yoshida R, Ohkuri T, Shigemura N, Ninomiya Y., Modulation and transmission of sweet taste information for energy homeostasis., Ann N Y Acad Sci., 1170:102-6., 2009.07.
20. 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.
21. Yoshida R, Shigemura N, Sanematsu K, Yasumatsu K, Ishizuka S, Ninomiya Y., Taste responsiveness of fungiform taste cells with action potentials., J Neurophysiol., 96(6):3088-95., 2006.12.
22. Sanematsu K, Yasumatsu K, Yoshida R, Shigemura N, Ninomiya Y., Mouse strain differences in Gurmarin-sensitivity of sweet taste responses are not associated with polymorphisms of the sweet receptor gene, Tas1r3., Chemical Senses, 10.1093/chemse/bji041, 30, 6, 491-496, 30(6):491-6., 2005.07.
23. Yoshida R, Sanematsu K, Shigemura N, Yasumatsu K, Ninomiya Y., Taste receptor cells responding with action potentials to taste stimuli and their molecular expression of taste related genes., Chemical Senses, 10.1093/chemse/bjh092, 30, I19-i20, 30 Suppl 1:i19-20., 2005.01.