Kyudai News No26 page 13/28

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Kyudai News No26

Kyudai News No.26 12expected to lead to the discovery of taste-modifyingsubstances and drugs that will help in preventing andtreating lifestyle-related diseases and obesity. In the future,we aim to continue to unravel the sweet taste receptoractivation and suppression mechanism by revealing theinteraction between receptors and sweet substances withvarious different structures, as well as between receptorsand other taste-modifying substances, such as miraculin,which causes sour taste to sweet. Based on these properties,we would also like to apply the knowledge that we havegained to the screening of new functional substances thatcould act on the different functions of each organ with thesame sensors, as well as to the olafactory receptor systemand molecular functions relating to the receptors forbitterness and umami, which are also G protein-coupledreceptors.PUBLICATION*1 Sanematsu K, Kusakabe Y, Shigemura N, Hirokawa T,Nakamura S, Imoto T, Ninomiya Y (2014) MolecularMechanisms for Sweet-suppressing Effect of Gymnemic Acids.J. Biol. Chem. 289(37):25711-25720.*2 Kawai K, Sugimoto K, Nakashima K, Miura H, Ninomiya Y(2000) Leptin as a modulator of sweet taste sensitivities inmice. Proc. Natl. Acad. Sci. U. S. A. 97(20):11044-11049.*3 Yoshida R, Ohkuri T, Jyotaki M, Yasuo T, Horio N, YasumatsuK, Sanematsu K, Shigemura N, Yamamoto T, Margolskee RF,Ninomiya Y (2010) Endocannabinoids selectively enhancesweet taste. Proc. Natl. Acad. Sci. U. S. A. 107(2):935-939.*4 Shigemura N, Iwata S, Yasumatsu K, Ohkuri T, Horio N,Sanematsu K, Yoshida R, Margolskee RF, Ninomiya Y (2013)Angiotensin II modulates salty and sweet taste sensitivities. J.Neurosci. 33(15):6267-6277.*5 Talavera K, Yasumatsu K, Voets T, Droogmans G, ShigemuraN, Ninomiya Y, Margolskee RF, Nilius B (2005) Heat activationof TRPM5 underlies thermal sensitivity of sweet taste. Nature438(7070):1022-1025.*6 Damak S, Rong M, Yasumatsu K, Kokrashvili Z, Varadarajan V,Zou S, Jiang P, Ninomiya Y, Margolskee RF (2003) Detection ofsweet and umami taste in the absence of taste receptor T1r3.Science 301(5634):850-853.Sweet TasteYuzoNinomiyaDistinguished Professor /Section of Oral Neuroscience,Faculty of Dental ScienceResearch and Development Center forTaste and Odor SensingNoriatsu ShigemuraAssociate Professor /Section of Oral Neuroscience,Faculty of Dental ScienceKeisuke SanematsuAssistant Professor /Section of Oral Neuroscience,Faculty of Dental ScienceFigure 　The Suppression Mechanism ofGymnemic Acids(A) Sweet cells are organized in taste buds embedded within the oralcavity. Sweet cells express sweet receptor T1R2/T1R3 composed ofan amino-terminal domain (ATD), a cysteine-rich domain (CRD), and atransmembrane domain (TMD).Gymnemic acid I acts on the human T1R3 TMD.(B) Molecular model showing the binding of gymnemic acid I in thehuman (h)T1R3 TMD.Left: Whole / Right: Detail