Updated on 2026/03/07

写真a

 
ISHIMARU YOSHIRO
 
Organization
Undergraduate School School of Agriculture Professor
Title
Professor
Homepage
https://www.foodfunction.jp/
External link

Degree

  • Doctor(Agriculture) ( 2003.3   The University of Tokyo )

  • Master(Agriculture) ( 2000.3   The University of Tokyo )

Research Interests

  • Taste signal transduction

  • 味覚シグナリング

Research Areas

  • Life sciences / Food sciences

  • Life sciences / Molecular biology

Education

  • The University of Tokyo   Graduate School of Agricultural and Life Sciences   Applied Biological Chemistry

    2000.4 - 2003.3

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    Country/Region： Japan

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  • The University of Tokyo   Graduate School of Agricultural and Life Sciences   Applied Biological Chemistry

    1998.4 - 2000.3

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    Country/Region： Japan

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  • The University of Tokyo

    1996.4 - 1998.3

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    Country/Region： Japan

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  • The University of Tokyo

    1994.4 - 1996.3

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Research History

  • Meiji University   School of Agriculture Department of Agricultural Chemistry   Professor

    2022.4

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  • Meiji University   School of Agriculture Department of Agricultural Chemistry   Associate Professor

    2017.4 - 2022.3

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  • The University of Tokyo   College of Arts and Sciences

    2016.4 - 2022.3

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  • The University of Tokyo   Graduate School of Agricultural and Life Sciences   Associate Professor (non-tenured)

    2014.1 - 2017.3

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  • The University of Tokyo   Graduate School of Agricultural and Life Sciences

    2008.4 - 2013.12

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  • Atomi University

    2008.4 - 2013.3

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  • The University of Tokyo   Graduate School of Agricultural and Life Sciences

    2007.4 - 2008.3

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  • Duke University   Research Associate

    2007.2 - 2007.3

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  • Duke University   日本学術振興会海外特別研究員

    2005.2 - 2007.1

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  • The University of Tokyo   Graduate School of Agricultural and Life Sciences

    2004.4 - 2005.1

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  • The University of Tokyo   Graduate School of Agricultural and Life Sciences   Special researcher of the Japan Society for the Promotion of Science

    2002.4 - 2004.3

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Professional Memberships

Committee Memberships

  • 日本農芸化学会   関東支部幹事  

    2023.5   

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    Committee type：Academic society

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  • 日本学術振興会   特別研究員等審査会専門委員  

    2019.7 - 2020.6   

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    Committee type：Academic society

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  • 日本農芸化学会   英文誌編集委員会委員  

    2019.3 - 2023.2   

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    Committee type：Academic society

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  • 日本農芸化学会   産学官学術交流委員会幹事  

    2013.4 - 2015.3   

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    Committee type：Academic society

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Papers

  • Fatty acid composition in 2-monoacylglycerol modulates GLP-1 secretion

    Yui Funatsu, Nozomi Takahashi, Yukiko Yamazaki, Hitoshi Watanabe, Tomoya Nakagita, Yoshiro Ishimaru, Kentaro Nakamura, Kentaro Kaneko

    Biochemical and Biophysical Research Communications   2025.9

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    Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.bbrc.2025.152546

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  • Evolutionary origins of bitter taste receptors in jawed vertebrates. Reviewed International journal

    Akihiro Itoigawa, Yasuka Toda, Shigehiro Kuraku, Yoshiro Ishimaru

    Current biology : CB   34 ( 7 )   R271-R272   2024.4

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    Taste is a sense that detects information about nutrients and toxins in foods. Of the five basic taste qualities, bitterness is associated with the detection of potentially harmful substances like plant alkaloids. In bony vertebrates, type 2 taste receptors (T2Rs), which are G-protein-coupled receptors (GPCRs), act as bitter taste receptors1,2. In vertebrates, six GPCR gene families are described as chemosensory receptor genes, encoding taste receptor families (T1Rs and T2Rs) and olfactory receptor families (ORs, V1Rs, V2Rs, and TAARs). These families of receptors have been found in all major jawed vertebrate lineages, except for the T2Rs, which are confined to bony vertebrates3. Therefore, T2Rs are believed to have emerged later than the other chemosensory receptor genes in the bony vertebrate lineage. So far, only the genomes of two cartilaginous fish species have been mined for TAS2R genes, which encode T2Rs4. Here, we identified novel T2Rs in elasmobranchs, namely selachimorphs (sharks) and batoids (rays, skates, and their close relatives) by an exhaustive search covering diverse cartilaginous fishes. Using functional and mRNA expression analyses, we demonstrate that their T2Rs are expressed in the oral taste buds and contribute to the detection of bitter compounds. This finding indicates the early origin of T2Rs in the common ancestor of jawed vertebrates.

    DOI： 10.1016/j.cub.2024.02.024

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  • A vertebrate-wide catalogue of T1R receptors reveals diversity in taste perception Reviewed

    Nishihara, H., Toda, Y., Kuramoto, T., Kamohara, K., Goto, A., Hoshino, K., Okada, S., Kuraku, S., Okabe, M., Ishimaru, Y.

    Nature Ecology and Evolution   8 ( 1 )   111 - 120   2024

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    DOI： 10.1038/s41559-023-02258-8

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  • Expression profiles and functional characterization of common carp (Cyprinus carpio) T2Rs Reviewed

    Shimizu, T., Kubozono, T., Asaoka, R., Toda, Y., Ishimaru, Y.

    Biochemistry and Biophysics Reports   28   101123 - 101123   2021.12

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    Authorship：Last author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

    DOI： 10.1016/j.bbrep.2021.101123

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  • TMC4 is a novel chloride channel involved in high-concentration salt taste sensation. Reviewed

    Yoichi Kasahara, Masataka Narukawa, Yoshiro Ishimaru, Shinji Kanda, Chie Umatani, Yasunori Takayama, Makoto Tominaga, Yoshitaka Oka, Kaori Kondo, Takashi Kondo, Ayako Takeuchi, Takumi Misaka, Keiko Abe, Tomiko Asakura

    The journal of physiological sciences : JPS   71 ( 1 )   23 - 23   2021.8

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    "Salty taste" sensation is evoked when sodium and chloride ions are present together in the oral cavity. The presence of an epithelial cation channel that receives Na+ has previously been reported. However, no molecular entity involving Cl- receptors has been elucidated. We report the strong expression of transmembrane channel-like 4 (TMC4) in the circumvallate and foliate papillae projected to the glossopharyngeal nerve, mediating a high-concentration of NaCl. Electrophysiological analysis using HEK293T cells revealed that TMC4 was a voltage-dependent Cl- channel and the consequent currents were completely inhibited by NPPB, an anion channel blocker. TMC4 allowed permeation of organic anions including gluconate, but their current amplitudes at positive potentials were less than that of Cl-. Tmc4-deficient mice showed significantly weaker glossopharyngeal nerve response to high-concentration of NaCl than the wild-type littermates. These results indicated that TMC4 is a novel chloride channel that responds to high-concentration of NaCl.

    DOI： 10.1186/s12576-021-00807-z

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  • Evolution of the primate glutamate taste sensor from a nucleotide sensor. Reviewed International journal

    Yasuka Toda, Takashi Hayakawa, Akihiro Itoigawa, Yosuke Kurihara, Tomoya Nakagita, Masahiro Hayashi, Ryuichi Ashino, Amanda D Melin, Yoshiro Ishimaru, Shoji Kawamura, Hiroo Imai, Takumi Misaka

    Current biology : CB   31 ( 20 )   4641 - 4649   2021.8

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    Taste perception plays an essential role in food selection. Umami (savory) tastes are sensed by a taste receptor complex, T1R1/T1R3, that detects proteinogenic amino acids.1 High sensitivity to l-glutamate (l-Glu) is a characteristic of human T1R1/T1R3, but the T1R1/T1R3 of other vertebrates does not consistently show this l-Glu response.1,2 Here, we demonstrate that the l-Glu sensitivity of T1R1/T1R3 is a derived state that has evolved repeatedly in large primates that rely on leaves as protein sources, after their divergence from insectivorous ancestors. Receptor expression experiments show that common amino acid substitutions at ligand binding sites that render T1R1/T1R3 sensitive to l-Glu occur independently at least three times in primate evolution. Meanwhile T1R1/T1R3 senses 5'-ribonucleotides as opposed to l-Glu in several mammalian species, including insectivorous primates. Our chemical analysis reveal that l-Glu is one of the major free amino acids in primate diets and that insects, but not leaves, contain large amounts of free 5'-ribonucleotides. Altering the ligand-binding preference of T1R1/T1R3 from 5'-ribonucleotides to l-Glu might promote leaf consumption, overcoming bitter and aversive tastes. Altogether, our results provide insight into the foraging ecology of a diverse mammalian radiation and help reveal how evolution of sensory genes facilitates invasion of new ecological niches.

    DOI： 10.1016/j.cub.2021.08.002

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  • Early origin of sweet perception in the songbird radiation. Reviewed International journal

    Yasuka Toda, Meng-Ching Ko, Qiaoyi Liang, Eliot T Miller, Alejandro Rico-Guevara, Tomoya Nakagita, Ayano Sakakibara, Kana Uemura, Timothy Sackton, Takashi Hayakawa, Simon Yung Wa Sin, Yoshiro Ishimaru, Takumi Misaka, Pablo Oteiza, James Crall, Scott V Edwards, William Buttemer, Shuichi Matsumura, Maude W Baldwin

    Science (New York, N.Y.)   373 ( 6551 )   226 - 231   2021.7

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    Early events in the evolutionary history of a clade can shape the sensory systems of descendant lineages. Although the avian ancestor may not have had a sweet receptor, the widespread incidence of nectar-feeding birds suggests multiple acquisitions of sugar detection. In this study, we identify a single early sensory shift of the umami receptor (the T1R1-T1R3 heterodimer) that conferred sweet-sensing abilities in songbirds, a large evolutionary radiation containing nearly half of all living birds. We demonstrate sugar responses across species with diverse diets, uncover critical sites underlying carbohydrate detection, and identify the molecular basis of sensory convergence between songbirds and nectar-specialist hummingbirds. This early shift shaped the sensory biology of an entire radiation, emphasizing the role of contingency and providing an example of the genetic basis of convergence in avian evolution.

    DOI： 10.1126/science.abf6505

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  • Erratum: Evolution of the primate glutamate taste sensor from a nucleotide sensor (Current Biology (2021) 31(20) (4641–4649.e5), (S0960982221010745), (10.1016/j.cub.2021.08.002))

    Toda, Y., Hayakawa, T., Itoigawa, A., Kurihara, Y., Nakagita, T., Hayashi, M., Ashino, R., Melin, A.D., Ishimaru, Y., Kawamura, S., Imai, H., Misaka, T.

    Current Biology   31 ( 20 )   2021

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    DOI： 10.1016/j.cub.2021.09.079

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  • Positive/Negative Allosteric Modulation Switching in an Umami Taste Receptor (T1R1/T1R3) by a Natural Flavor Compound, Methional. Reviewed International journal

    Toda Y, Nakagita T, Hirokawa T, Yamashita Y, Nakajima A, Narukawa M, Ishimaru Y, Uchida R, Misaka T

    Scientific reports   8 ( 1 )   11796 - 11796   2018.8

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    Taste is a vital sensation for vertebrates, enabling the detection of nutritionally important substances or potential toxins. A heteromeric complex of two class C GPCRs, T1R1 and T1R3, was identified as the umami (savory) taste receptor. Amino acids and 5'-ribonucleotides are well known to be natural ligands for human T1R1/T1R3. In this study, we reveal that methional, which is a familiar flavor component in foods, is an allosteric modulator of T1R1/T1R3. Receptor expression experiments showed that methional served as a positive allosteric modulator (PAM) of human T1R1/T1R3 and functioned as a negative allosteric modulator (NAM) of mouse T1R1/T1R3. Although amino acids and 5'-ribonucleotides bound to the extracellular domain of T1R1, the use of interspecies chimeric receptors demonstrated that methional interacted with the transmembrane domain of T1R1. Site-directed mutagenesis and molecular modeling showed that methional could potentially bind at two distinct sites in the transmembrane domain of T1R1 and that the amino acid residues in the bottom of the allosteric pocket engendered the switch between the PAM and NAM modes, which could contribute to switching the binding position of methional. These results may be applicable for elucidating the molecular mechanisms underlying ligand recognition by other class C GPCRs.

    DOI： 10.1038/s41598-018-30315-x

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  • Gene Expression Analysis of the Effect of Ischemic Infarction in Whole Blood Reviewed

    Ayako Takuma, Arata Abe, Yoshikazu Saito, Chikako Nito, Masayuki Ueda, Yoshiro Ishimaru, Hideki Harada, Keiko Abe, Kazumi Kimura, Tomiko Asakura

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   18 ( 11 )   2017.11

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    DOI： 10.3390/ijms18112335

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  • A large increase of sour taste receptor cells in Skn-1-deficient mice does not alter the number of their sour taste signal-transmitting gustatory neurons Reviewed

    Naohiro Maeda, Masataka Narukawa, Yoshiro Ishimaru, Kurumi Yamamoto, Takumi Misaka, Keiko Abe

    NEUROSCIENCE LETTERS   648   53 - 58   2017.5

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    DOI： 10.1016/j.neulet.2017.03.046

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  • Olfactory receptor accessory proteins play crucial roles in receptor function and gene choice Reviewed

    Ruchira Sharma, Yoshiro Ishimaru, Ian Davison, Kentaro Ikegami, Ming-Shan Chien, Helena You, Quiyi Chi, Momoka Kubota, Masafumi Yohda, Michael Ehlers, Hiroaki Matsunami

    ELIFE   6   2017.3

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    DOI： 10.7554/eLife.21895

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  • Expanding frontiers in weight-control research explored by young investigators Reviewed

    Yoshiro Ishimaru, Chisayo Kozuka, Kenichiro Nakajima, Tsutomu Sasaki

    JOURNAL OF PHYSIOLOGICAL SCIENCES   67 ( 1 )   83 - 95   2017.1

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    DOI： 10.1007/s12576-016-0495-7

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  • Variation in ligand responses of the bitter taste receptors TAS2R1 and TAS2R4 among New World monkeys Reviewed

    Kei Tsutsui, Masahiro Otoh, Kodama Sakurai, Nami Suzuki-Hashido, Takashi Hayakawa, Takumi Misaka, Yoshiro Ishimaru, Filippo Aureli, Amanda D. Melin, Shoji Kawamura, Hiroo Imai

    BMC EVOLUTIONARY BIOLOGY   16 ( 1 )   208   2016.10

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    DOI： 10.1186/s12862-016-0783-0

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  • Spontaneous Bilateral Cervical Internal Carotid and Vertebral Artery Dissection in a Japanese Patient without Collagen Vascular Disease with pecial Reference to Single-Nucleotide Polymorphisms Reviewed

    Arata Abe, Chikako Nito, Yuki Sakamoto, Akane Nogami, Hiroyuki Hokama, Shiro Takahashi, Kumiko Kirita, Masayuki Ueda, Yoshiro Ishimaru, Kazumi Kimura

    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES   25 ( 8 )   E114 - E117   2016.8

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    DOI： 10.1016/j.jstrokecerebrovasdis.2016.04.027

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  • Amino acid residues of bitter taste receptor TAS2R16 that determine sensitivity in primates to β-glycosides. Reviewed

    Imai H, Suzuki-Hashido N, Ishimaru Y, Sakurai T, Yin L, Pan W, Ishiguro M, Masuda K, Abe K, Misaka T, Hirai H

    Biophysics and physicobiology   13   165 - 171   2016.7

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    Language：English   Publisher：The Biophysical Society of Japan  

    <p>In mammals, bitter taste is mediated by TAS2Rs, which belong to the family of seven transmembrane G protein-coupled receptors. Since TAS2Rs are directly involved in the interaction between mammals and their dietary sources, it is likely that these genes evolved to reflect species-specific diets during mammalian evolution. Here, we analyzed the amino acids responsible for the difference in sensitivities of TAS2R16s of various primates using a cultured cell expression system. We found that the sensitivity of TAS2R16 varied due to several amino acid residues. Mutation of amino acid residues at E86T, L247M, and V260F in human and langur TAS2R16 for mimicking the macaque TAS2R16 decreased the sensitivity of the receptor in an additive manner, which suggests its contribution to the potency of salicin, possibly via direct interaction. However, mutation of amino acid residues 125 and 133 in human TAS2R16, which are situated in helix 4, to the macaque sequence increased the sensitivity of the receptor. These results suggest the possibility that bitter taste sensitivities evolved independently by replacing specific amino acid residues of TAS2Rs in different primate species to adapt to species-specific food.</p>

    DOI： 10.2142/biophysico.13.0_165

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  • Catecholamines Facilitate Fuel Expenditure and Protect Against Obesity via a Novel Network of the Gut-Brain Axis in Transcription Factor Skn-1-deficient Mice Reviewed

    Shota Ushiama, Yoshiro Ishimaru, Masataka Narukawa, Misako Yoshioka, Chisayo Kozuka, Naoki Watanabe, Makoto Tsunoda, Naomi Osakabe, Tomiko Asakura, Hiroaki Masuzaki, Keiko Abe

    EBIOMEDICINE   8   60 - 71   2016.6

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    DOI： 10.1016/j.ebiom.2016.04.031

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  • Expression of serotonin receptor genes in cranial ganglia Reviewed

    Naohiro Maeda, Makoto Ohmoto, Kurumi Yamamoto, Azusa Kurokawa, Masataka Narukawa, Yoshiro Ishimaru, Takumi Misaka, Ichiro Matsumoto, Keiko Abe

    NEUROSCIENCE LETTERS   617   46 - 51   2016.3

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    DOI： 10.1016/j.neulet.2016.01.050

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  • A predictive model based on surface electromyography to assess the easiness of deglutition of dysphagia diets Reviewed

    Yuki Kayanuma, Reiko Ueda, Michiko Minami, Arata Abe, Kazumi Kimura, Junko Funaki, Yoshiro Ishimaru, Tomiko Asakura

    J. Food Process. Technol   7:7   1 - 7   2016

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  • Bitterness-masking effect of fatty acids by cluster formation with bitter substances via hydrophobic and ionic interactions Reviewed

    Kayako Ogi, Haruyuki Yamashita, Tohru Terada, Ryousuke Homma, Akiko Ibuka-Shimizu, Etsuro Yoshimura, Yoshiro Ishimaru, Keiko Abe, Tomiko Asakura

    63, 8493-8500   2015.9

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    DOI： 10.1021/acs.jafc.5b03193

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  • Long-Chain Fatty Acids Elicit a Bitterness-Masking Effect on Quinine and Other Nitrogenous Bitter Substances by Formation of Insoluble Binary Complexes Reviewed

    Kayako Ogi, Haruyuki Yamashita, Tohru Terada, Ryousuke Homma, Akiko Shimizu-Ibuka, Etsuro Yoshimura, Yoshiro Ishimaru, Keiko Abe, Tomiko Asakura

    JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY   63 ( 38 )   8493 - 8500   2015.9

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    DOI： 10.1021/acs.jafc.5b03193

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  • Long-Chain Fatty Acids Elicit a Bitterness-Masking Effect on Quinine and Other Nitrogenous Bitter Substances by Formation of Insoluble Binary Complexes. Reviewed International journal

    Ogi Kayako, Yamashita Haruyuki, Terada Tohru, Homma Ryousuke, Shimizu-Ibuka Akiko, Yoshimura Etsuro, Ishimaru Yoshiro, Abe Keiko, Asakura Tomiko

    Journal of agricultural and food chemistry   63 ( 38 )   8493-500 - 500   2015.9

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    We have previously found that fatty acids can mask the bitterness of certain nitrogenous substances through direct molecular interactions. Using isothermal titration calorimetry, we investigated the interactions between sodium oleate and 22 bitter substances. The hydrochloride salts of quinine, promethazine, and propranolol interacted strongly with fatty acids containing 12 or more carbon atoms. The (1)H NMR spectra of these substances, obtained in the presence of the sodium salts of the fatty acids in dimethyl sulfoxide, revealed the formation of hydrogen bonds between the nitrogen atoms of the bitter substances and the carboxyl groups of the fatty acids. When sodium laurate and the hydrochloride salt of quinine were mixed in water, an equimolar complex formed as insoluble heterogeneous needlelike crystals. These results suggested that fatty acids interact directly with bitter substances through hydrogen bonds and hydrophobic interactions to form insoluble binary complexes that mask bitterness.

    DOI： 10.1021/acs.jafc.5b03193

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  • Rapid Expansion of Phenylthiocarbamide Non-Tasters among Japanese Macaques Reviewed

    Nami Suzuki-Hashido, Takashi Hayakawa, Atsushi Matsui, Yasuhiro Go, Yoshiro Ishimaru, Takumi Misaka, Keiko Abe, Hirohisa Hirai, Yoko Satta, Hiroo Imai

    PLOS ONE   10 ( 7 )   e0132016   2015.7

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    DOI： 10.1371/journal.pone.0132016

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  • Molecular mechanisms underlying the reception and transmission of sour taste information Reviewed

    Yoshiro Ishimaru

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   79 ( 2 )   171 - 176   2015.2

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    DOI： 10.1080/09168451.2014.975187

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  • Additional Nitrogen Fertilization at Heading Time of Rice Down-Regulates Cellulose Synthesis in Seed Endosperm Reviewed

    Keiko Midorikawa, Masaharu Kuroda, Kaede Terauchi, Masako Hoshi, Sachiko Ikenaga, Yoshiro Ishimaru, Keiko Abe, Tomiko Asakura

    PLOS ONE   9 ( 6 )   e98738   2014.6

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    DOI： 10.1371/journal.pone.0098738

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  • The molecular basis of sour sensing in mammals Reviewed

    Jianghai Ho, Hiroaki Matsunami, Yoshiro Ishimaru

    Molecular Genetics of Dysregulated pH Homeostasis   27 - 43   2014.1

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    Language：English   Publishing type：Part of collection (book)   Publisher：Springer New York  

    DOI： 10.1007/978-1-4939-1683-2_3

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  • Two Distinct Determinants of Ligand Specificity in T1R1/T1R3 (the Umami Taste Receptor) Reviewed

    Yasuka Toda, Tomoya Nakagita, Takashi Hayakawa, Shinji Okada, Masataka Narukawa, Hiroo Imai, Yoshiro Ishimaru, Takumi Misaka

    JOURNAL OF BIOLOGICAL CHEMISTRY   288 ( 52 )   36863 - 36877   2013.12

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    DOI： 10.1074/jbc.M113.494443

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  • Experimental detection of proteolytic activity in a signal peptide peptidase of Arabidopsis thaliana Reviewed

    Masako Hoshi, Yu Ohki, Keisuke Ito, Taisuke Tomita, Takeshi Iwatsubo, Yoshiro Ishimaru, Keiko Abe, Tomiko Asakura

    BMC BIOCHEMISTRY   14   16   2013.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1186/1471-2091-14-16

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  • Oral and extra-oral taste perception Invited Reviewed

    Kurumi Yamamoto, Yoshiro Ishimaru

    Seminars in Cell and Developmental Biology   24 ( 3 )   240 - 246   2013

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    DOI： 10.1016/j.semcdb.2012.08.005

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  • Expression Analysis of Taste Signal Transduction Molecules in the Fungiform and Circumvallate Papillae of the Rhesus Macaque, Macaca mulatta Reviewed

    Yoshiro Ishimaru, Miki Abe, Tomiko Asakura, Hiroo Imai, Keiko Abe

    PLOS ONE   7 ( 9 )   e45426   2012.9

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    DOI： 10.1371/journal.pone.0045426

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  • Functional diversity of bitter taste receptor TAS2R16 in primates Reviewed

    Hiroo Imai, Nami Suzuki, Yoshiro Ishimaru, Takanobu Sakurai, Lijie Yin, Wenshi Pan, Keiko Abe, Takumi Misaka, Hirohisa Hirai

    BIOLOGY LETTERS   8 ( 4 )   652 - 656   2012.8

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    DOI： 10.1098/rsbl.2011.1251

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  • Identification of Bitterness-Masking Compounds from Cheese Reviewed

    Ryousuke Homma, Haruyuki Yamashita, Junko Funaki, Reiko Ueda, Takanobu Sakurai, Yoshiro Ishimaru, Keiko Abe, Tomiko Asakura

    JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY   60 ( 18 )   4492 - 4499   2012.5

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    DOI： 10.1021/jf300563n

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  • The response of PKD1L3?/?PKD2L1 to acid stimuli is inhibited by capsaicin and its pungent analogs Reviewed

    Sho Ishii, Azusa Kurokawa, Mikiya Kishi, Keigo Yamagami, Shinji Okada, Yoshiro Ishimaru, Takumi Misaka

    FEBS JOURNAL   279 ( 10 )   1857 - 1870   2012.5

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    DOI： 10.1111/j.1742-4658.2012.08566.x

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  • Global gene expression profiles in developing soybean seeds Reviewed

    Tomiko Asakura, Tomoko Tamura, Kaede Terauchi, Tomoyo Narikawa, Kazuhiro Yagasaki, Yoshiro Ishimaru, Keiko Abe

    PLANT PHYSIOLOGY AND BIOCHEMISTRY   52   147 - 153   2012.3

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    DOI： 10.1016/j.plaphy.2011.12.007

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  • 3PT189 Functional diversity of bitter taste receptor TAS2R16 by amino acid substitution(The 50th Annual Meeting of the Biophysical Society of Japan)

    Imai Hiroo, Suzuki Nami, Ishimaru Yoshiro, Sakurai Takanobu, Yin Lijie, Pan Wenshi, Abe Keiko, Misaka Takumi, Hirai Hirohisa

    Seibutsu Butsuri   52   S174   2012

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    DOI： 10.2142/biophys.52.S174_1

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  • Genetic tracing of the gustatory neural pathway originating from Pkd1l3-expressing type III taste cells in circumvallate and foliate papillae Reviewed

    Kurumi Yamamoto, Yoshiro Ishimaru, Makoto Ohmoto, Ichiro Matsumoto, Tomiko Asakura, Keiko Abe

    JOURNAL OF NEUROCHEMISTRY   119 ( 3 )   497 - 506   2011.11

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    DOI： 10.1111/j.1471-4159.2011.07443.x

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  • Analysis of the interaction of food components with model lingual epithelial cells: the case of sweet proteins Reviewed

    Tomiko Asakura, Motohiro Miyano, Haruyuki Yamashita, Takanobu Sakurai, Ken-ichiro Nakajima, Keisuke Ito, Takumi Misaka, Yoshiro Ishimaru, Keiko Abe

    FLAVOUR AND FRAGRANCE JOURNAL   26 ( 4 )   274 - 278   2011.7

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    DOI： 10.1002/ffj.2073

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  • Sour Taste Responses in Mice Lacking PKD Channels Reviewed

    Nao Horio, Ryusuke Yoshida, Keiko Yasumatsu, Yuchio Yanagawa, Yoshiro Ishimaru, Hiroaki Matsunami, Yuzo Ninomiya

    PLOS ONE   6 ( 5 )   e20007   2011.5

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    DOI： 10.1371/journal.pone.0020007

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  • The single pore residue Asp(523) in PKD2L1 determines Ca2+ permeation of the PKD1L3/PKD2L1 complex Reviewed

    Chisato Fujimoto, Yoshiro Ishimaru, Yuka Katano, Takumi Misaka, Tatsuya Yamasoba, Tomiko Asakura, Keiko Abe

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   404 ( 4 )   946 - 951   2011.1

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    DOI： 10.1016/j.bbrc.2010.12.086

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  • Surface Plasmon Resonance Analysis on Interactions of Food Components with a Taste Epithelial Cell Model Reviewed

    Motohiro Miyano, Haruyuki Yamashita, Takanobu Sakurai, Ken-ichiro Nakajima, Keisuke Ito, Takumi Misaka, Yoshiro Ishimaru, Keiko Abe, Tomiko Asakura

    JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY   58 ( 22 )   11870 - 11875   2010.11

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    DOI： 10.1021/jf102573w

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  • The human bitter taste receptor, hTAS2R16, discriminates slight differences in the configuration of disaccharides Reviewed

    Takanobu Sakurai, Takumi Misaka, Yohei Ueno, Masaji Ishiguro, Shinji Matsuo, Yoshiro Ishimaru, Tomiko Asakura, Keiko Abe

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   402 ( 4 )   595 - 601   2010.11

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    DOI： 10.1016/j.bbrc.2010.10.059

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  • Interaction between PKD1L3 and PKD2L1 through their transmembrane domains is required for localization of PKD2L1 at taste pores in taste cells of circumvallate and foliate papillae Reviewed

    Yoshiro Ishimaru, Yuka Katano, Kurumi Yamamoto, Masato Akiba, Takumi Misaka, Richard W. Roberts, Tomiko Asakura, Hiroaki Matsunami, Keiko Abe

    FASEB JOURNAL   24 ( 10 )   4058 - 4067   2010.10

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    DOI： 10.1096/fj.10-162925

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  • Characterization of the beta-D-Glucopyranoside Binding Site of the Human Bitter Taste Receptor hTAS2R16 Reviewed

    Takanobu Sakurai, Takumi Misaka, Masaji Ishiguro, Katsuyoshi Masuda, Taishi Sugawara, Keisuke Ito, Takuya Kobayashi, Shinji Matsuo, Yoshiro Ishimaru, Tomiko Asakura, Keiko Abe

    JOURNAL OF BIOLOGICAL CHEMISTRY   285 ( 36 )   28373 - 28378   2010.9

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    DOI： 10.1074/jbc.M110.144444

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  • Expression of the Stress-Related Genes for Glutathione S-Transferase and Ascorbate Peroxidase in the Most-Glycinin-Deficient Soybean Cultivar Tousan205 during Seed Maturation Reviewed

    Tomoyo Narikawa, Tomoko Tamura, Kazuhiro Yagasaki, Kaede Terauchi, Kazutsuka Sanmiya, Yoshiro Ishimaru, Keiko Abe, Tomiko Asakura

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   74 ( 9 )   1976 - 1979   2010.9

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    DOI： 10.1271/bbb.100479

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  • Signal peptide peptidases are expressed in the shoot apex of rice, localized to the endoplasmic reticulum Reviewed

    Tomoko Tamura, Masaharu Kuroda, Tetsuo Oikawa, Junko Kyozuka, Kaede Terauchi, Yoshiro Ishimaru, Keiko Abe, Tomiko Asakura

    PLANT CELL REPORTS   28 ( 11 )   1615 - 1621   2009.11

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    DOI： 10.1007/s00299-009-0760-9

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  • Acidic Substances Added in the Oral Cavity Reduce our Bitter Taste Sensation by pH-Dependent Inhibition of hTAS2R Response Reviewed

    Takanobu Sakurai, Takumi Misaka, Toshitada Nagai, Yoshiro Ishimaru, Shinji Matsuo, Tomiko Asakura, Keiko Abe

    CHEMICAL SENSES   34 ( 7 )   A81 - A81   2009.9

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  • Acetic acid activates PKD1L3-PKD2L1 channel-A candidate sour taste receptor Reviewed

    Sho Ishii, Takumi Misaka, Mikiya Kishi, Takayuki Kaga, Yoshiro Ishimaru, Keiko Abe

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   385 ( 3 )   346 - 350   2009.7

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    DOI： 10.1016/j.bbrc.2009.05.069

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  • pH-Dependent Inhibition of the Human Bitter Taste Receptor hTAS2R16 by a Variety of Acidic Substances Reviewed

    Takanobu Sakurai, Takumi Misaka, Toshitada Nagai, Yoshiro Ishimaru, Shinji Matsuo, Tomiko Asakura, Keiko Abe

    JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY   57 ( 6 )   2508 - 2514   2009.3

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    DOI： 10.1021/jf8040148

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  • Transient Receptor Potential (TRP) Channels and Taste Sensation Reviewed

    Y. Ishimaru, H. Matsunami

    JOURNAL OF DENTAL RESEARCH   88 ( 3 )   212 - 218   2009.3

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    DOI： 10.1177/0022034508330212

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  • Molecular mechanisms of taste transduction in vertebrates Reviewed

    Yoshiro Ishimaru

    ODONTOLOGY   97 ( 1 )   1 - 7   2009.1

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    DOI： 10.1007/s10266-008-0095-y

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  • Erratum: Molecular mechanisms of taste transduction in vertebrates (Odontology (2009) vol. 97 (1-7) 10.1007/s10266-008-0095-y)

    Ishimaru, Y.

    Odontology   97 ( 2 )   120 - 120   2009

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    DOI： 10.1007/s10266-009-0098-3

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  • Off-response property of an acid-activated cation channel complex PKD1L3-PKD2L1 Reviewed

    Hitoshi Inada, Fuminori Kawabata, Yoshiro Ishimaru, Tohru Fushiki, Hiroaki Matsunami, Makoto Tominaga

    EMBO REPORTS   9 ( 7 )   690 - 697   2008.7

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    DOI： 10.1038/embor.2008.89

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  • The candidate sour taste receptor, PKD2L1, is expressed by type III taste cells in the mouse Reviewed

    Shinji Kataoka, Ruibiao Yang, Yoshiro Ishimaru, Hiroaki Matsunami, Jean Sevigny, John C. Kinnamon, Thomas E. Finger

    CHEMICAL SENSES   33 ( 3 )   243 - 254   2008.3

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    DOI： 10.1093/chemse/bjm083

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  • 脊椎動物における味覚受容の分子基盤

    石丸喜朗

    実験医学   26 ( 4 )   522 - 528   2008

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  • Characterization of ligands for fish taste receptors Reviewed

    Hideaki Oike, Toshitada Nagai, Akira Furuyama, Shinji Okada, Yoshiko Aihara, Yoshiro Ishimaru, Takayuki Marui, Ichiro Matsumoto, Takumi Misaka, Keiko Abe

    JOURNAL OF NEUROSCIENCE   27 ( 21 )   5584 - 5592   2007.5

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    DOI： 10.1523/JNEUROSCI.0651-07.2007

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  • Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor Reviewed

    Yoshiro Ishimaru, Hitoshi Inada, Momoka Kubota, Hanyi Zhuang, Makoto Tominaga, Hiroaki Matsunami

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   103 ( 33 )   12569 - 12574   2006.8

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    DOI： 10.1073/pnas.0602702103

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  • Two families of candidate taste receptors in fishes Reviewed

    Y Ishimaru, S Okada, H Naito, T Nagai, A Yasuoka, Matsumoto, I, K Abe

    MECHANISMS OF DEVELOPMENT   122 ( 12 )   1310 - 1321   2005.12

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    DOI： 10.1016/j.mod.2005.07.005

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  • An actin-binding protein, CAP, is expressed in a subset of rat taste bud cells Reviewed

    Y Ishimaru, A Yasuoka, M Asano-Miyoshi, K Abe, A Emori

    NEUROREPORT   12 ( 2 )   233 - 235   2001.2

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  • A gustatory cyclic nucleotide-gated channels CNGgust, is expressed in the retina Reviewed

    T Misaka, Y Ishimaru, K Iwabuchi, Y Kusakabe, S Arai, Y Emori, K Abe

    NEUROREPORT   10 ( 4 )   743 - 746   1999.3

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MISC

  • Functional evolution of sweet taste receptors in the family Indriidae

    糸井川壮大, 戸田安香, 石丸喜朗, 今井啓雄

    霊長類研究   39 ( Supplement )   2023

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  • Relationship between the nucleotide sensitivity of T1R1/T1R3 and diets in primates

    戸田安香, 早川卓志, 糸井川壮大, 栗原洋介, 中北智哉, AMANDA Melin, 河村正二, 今井啓雄, 石丸喜朗, 三坂巧

    日本農芸化学会大会講演要旨集(Web)   2022   2022

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  • 味覚と嗅覚の進化 脊椎動物における味覚の多様性とその遺伝的要因

    戸田安香, 石丸喜朗, 三坂巧

    科学   92 ( 12 )   2022

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  • インドリ科における甘味受容体の機能多様性

    糸井川壮大, 戸田安香, 石丸喜朗, 今井啓雄

    霊長類研究   ( Supplement (CD-ROM) )   2022

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  • 粉末あるいは固形飼料を長期間摂取させたラットの視床における発現遺伝子の比較解析

    小川真奈, 永井俊匡, 齊藤美佳, 石丸喜朗, 阿部啓子, 阿部啓子, 朝倉富子

    日本農芸化学会大会講演要旨集(Web)   2017   2017

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  • 粉末あるいは固形飼料を長期間摂取させたラットの血圧調節と視床下部遺伝子発現変動

    齊藤美佳, 永井俊匡, 小川真奈, 石丸喜朗, 阿部啓子, 阿部啓子, 朝倉富子

    日本農芸化学会大会講演要旨集(Web)   2017   2017

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  • Catecholamines facilitate fuel expenditure and protect against obesity via a novel network of the gut-brain axis in transcription factor Skn-1 -deficient mice

    Yoshiro Ishimaru, Shota Ushiama, Masataka Narukawa, Misako Yoshioka, Chisayo Kozuka, Naoki Watanabe, Makoto Tsunoda, Naomi Osakabe, Tomiko Asakura, Hiroaki Masuzaki, Keiko Abe

    CHEMICAL SENSES   41 ( 9 )   E218 - E218   2016.11

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  • Loss of brush cells and taste cells in the gastrointestinal tract alters energy metabolism in Skn-1-deficient mice.

    Ishimaru Yoshiro, S. Ushiama, M. Narukawa, M. Yoshioka, C. Kozuka, N. Watanabe, N. Osakabe, T. Asakura, H. Masuzaki, K. Abe

    CHEMICAL SENSES   41 ( 4 )   415 - 416   2016.5

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  • 咀嚼頻度の異なる餌を摂取させたラットの行動および脳内発現遺伝子の比較解析

    田熊彩子, 永井俊匡, 石丸喜朗, 阿部啓子, 朝倉富子

    日本農芸化学会大会講演要旨集(Web)   2016   2016

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  • 粉餌あるいは固形餌を長期間摂取させたラットの脳内発現遺伝子の比較解析

    小川真奈, 永井俊匡, 齊藤美佳, 石丸喜朗, 阿部啓子, 朝倉富子

    日本農芸化学会大会講演要旨集(Web)   2016   2016

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  • Olfactory receptor accessory proteins RTP1 and RTP2 play a crucial role in receptor gene choice, development and odor detection

    Ruchira Sharma, Yoshiro Ishimaru, Ian Davison, Kentaro Ikegami, Hiroaki Matsunami

    CHEMICAL SENSES   40 ( 7 )   535 - 535   2015.9

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  • ニホンザルにおける苦味受容体TAS2R38の地域特異的な感受性変異

    鈴木南美, 松井淳, 郷康広, 石丸喜朗, 三坂巧, 阿部啓子, 平井啓久, 今井啓雄

    霊長類研究   27 ( Supplement )   26   2011.7

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  • 酸味受容体PKD1L3/PKD2L1のカルシウム透過に重要な酸性アミノ酸残基の同定

    石丸喜朗, 藤本千里, 片野佑香, 山岨達也, 朝倉富子, 阿部啓子

    日本農芸化学会大会講演要旨集   2011   208   2011.3

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  • 苦味受容体TAS2R16 感受性の種間差と分子機構 Reviewed

    今井啓雄, 鈴木南美, 松井淳, 郷康広, 石丸喜朗, 三坂巧, 阿部啓子, 平井啓久

    第27回日本霊長類学会大会 (2011/07/17, 犬山)   2011

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    DOI： 10.14907/primate.27.0.55.0

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  • PKD1L3/PKD2L1チャネル複合体による酸味受容の分子機構

    富永真琴, 富永真琴, 稲田仁, 石丸喜朗, 松波宏明

    日本生理学雑誌   71 ( 5 )   2009

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  • Off-response property of an acid sensing channel complex PKD1L3/PKD2L1

    Inada Hitoshi, Kawabata Fuminori, Ishimaru Yoshiro, Fushiki Tohru, Matsunami Hiroaki, Tominaga Makoto

    Proceedings of Annual Meeting of the Physiological Society of Japan   2008   079 - 079   2008

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    An acid-activated ion channel complex PKD1L3/PKD2L1 has been reported as a candidate of sour taste receptor molecules. In mouse tongue, PKD1L3 and PKD2L1 are co-expressed in a subset of taste receptor cells. PKD1L3 and PKD2L1 proteins can interact with each other, and co-expression of the PKD1L3 and PKD2L1 is necessary for their functional cell surface expression. Large currents are evoked by both citric acid and HCl in the PKD1L3/PKD2L1 expressed HEK293 cells. These results suggest that PKD1L3/PKD2L1 channel complex may function as sour taste receptors. Here, we report a unique property of PKD1L3/PKD2L1 channel complex, named as an off-response, which implies that the channel is activated upon the removal of acid stimulus. Acid-induced responses were observed only after the removal of an acidic solution with a pH lower than 3.0. A small increase in pH as low as 1.5 unit appears to be sufficient to activate the PKD1L3/PKD2L1 channels once exposed to the acidic solution with pH 2.5. These results indicate that the PKD1L3/PKD2L1 channel belongs to a novel type of ion channels, named as off-channels, activated by the removal of stimulus. The off-response property of PKD1L3/PKD2L1 channel may explain the physiological phenomena observed in sour taste sensation. <b>[J Physiol Sci. 2008;58 Suppl:S79]</b>

    DOI： 10.14849/psjproc.2008.0_079_4

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  • 酸味受容体候補PKD1L3/PDK2L1の発見とその解析

    石丸喜朗, 石丸喜朗, 稲田仁, 片岡真司, 久保田桃加, ZHUANG Hanyi, YANG Ruibiao, KINNAMON John C., FINGER Thomas E., 富永真琴, 富永真琴, 阿部啓子, 松波宏明

    日本農芸化学会大会講演要旨集   2008   2008

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  • ヒト苦味受容体hTAS2R16のリガンド認識に及ぼす酸性物質添加効果

    櫻井敬展, 櫻井敬展, 三坂巧, 永井俊匡, 石丸喜朗, 朝倉富子, 阿部啓子

    日本農芸化学会大会講演要旨集   2008   2008

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  • ゼブラフィッシュ味覚受容体の細胞外ループへの変異導入による機能差異

    永井俊匡, 大池秀明, 岡田晋治, 石黒正路, 石丸喜朗, 阿部啓子, 三坂巧

    日本農芸化学会大会講演要旨集   2008   2008

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  • 新規酸受容チャネル複合体PKD1L3/PKD2L1の電気生理学的解析

    稲田仁, 川端二功, 石丸喜朗, 久保田桃加, HANYI Zhuang, 松波宏明, 富永真琴

    生化学   2007   3P-0812 - 227   2007

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    Acid sensation is a critical cue to avoid spoiled foods or harmful solutions in animals. It has been reported that several ion channels activated by proton such as ASIC and HCN channels are involved in sour taste sensation. However, molecular mechanisms underlying sour taste sensation remain largely unclear. Here, we report a novel class of acid-activated ion channel complex PKD1L3/PKD2L1, as a candidate of sour taste receptor molecules. PKD1L3 and PKD2L1 are similar to members of polycistin family polycystin-1 and -2, whose defects are thought to cause autosomal dominant polycystic kidney diseases. TRP2L1 also belongs to transient receptor potential (TRP) channel family. In mouse tongue, PKD1L3 and PKD2L1 are co-expressed in a subset of taste receptor cells, which are distinct from taste cells having receptors for bitter, sweet, or umami tastants. PKD1L3 and PKD2L1 proteins can interact with each other, and co-expression of the PKD1L3 and PKD2L1 is necessary for their functional cell surface expression. Large currents are evoked by both weak and strong acids (citric acid and HCl, respectively) in the PKD1L3/PKD2L1 expressed HEK293 cells. EC<SUB>50</SUB> is pH 2.9 for citric acid and pH 2.7 for HCl, respectively. These results suggest that PKD1L3/PKD2L1 may function as sour taste receptors. <b>[J Physiol Sci. 2007;57 Suppl:S227]</b>

    DOI： 10.14849/psjproc.2007.0_227_4

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  • 魚類味覚受容体T2Rファミリーの機能解析

    永井俊匡, 大池秀明, 岡田晋治, 丸井隆之, 石丸喜朗, 三坂巧, 阿部啓子

    日本農芸化学会大会講演要旨集   2007   2007

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  • Two families of candidate taste receptors in fishes

    Y. Ishimaru, S. Okada, H. Naito, T. Nagai, A. Yasuoka, I. Matsumoto, K. Abe

    CHEMICAL SENSES   31 ( 5 )   A100 - A100   2006.6

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  • 魚類の味覚受容体候補ファミリーの同定

    内藤紘子, 岡田晋治, 石丸喜朗, 永井俊匡, 安岡顕人, 松本一朗, 阿部啓子

    日本農芸化学会大会講演要旨集   2006   2006

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  • ゼブラフィッシュ味蕾に発現するT2Rファミリー分子の機能解析

    永井俊匡, 大池秀明, 岡田晋治, 内藤紘子, 石丸喜朗, 安岡顕人, 松本一朗, 阿部啓子

    日本農芸化学会大会講演要旨集   2006   2006

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  • A gustatory cyclic nucleotide-gated channels CNGgust, is expressed in the retina

    T Misaka, Y Ishimaru, K Iwabuchi, Y Kusakabe, S Arai, Y Emori, K Abe

    NEUROREPORT   10 ( 4 )   743 - 746   1999.3

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Awards

  • 連合駿台会学術奨励賞

    2019.1   連合駿台会  

    石丸 喜朗

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  • バイオインダストリー奨励賞

    2018.10   バイオインダストリー協会  

    石丸 喜朗

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  • 三島海雲学術賞

    2017.7   三島海雲記念財団   食品成分の受容・伝達と生体応答の分子基盤

    石丸 喜朗

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  • 安藤百福賞 発明発見奨励賞

    2016.3   食創会   酸味受容体の発見

    石丸 喜朗

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  • 農芸化学奨励賞

    2012.3   日本農芸化学会   酸味受容体の発見とその味覚伝達機構の解明

    石丸 喜朗

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Research Projects

  • 味覚と消化機能の進化から紐解く果実食鳥類の求愛行動

    Grant number：22KK0079  2022.10 - 2025.3

    日本学術振興会  科学研究費助成事業  国際共同研究加速基金(国際共同研究強化(B))

    戸田 安香, 石丸 喜朗, 中北 智哉

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    Grant amount：\20150000 （ Direct Cost: \15500000 、 Indirect Cost：\4650000 ）

    感覚受容のシステムは、生物が外界に適応し繁栄するために、長い年月をかけて進化してきた。これまで当国際共同研究グループは、花蜜食鳥類であるハチドリや鳴禽類を対象に研究を行い、旨味受容体が糖を受容する能力を新たに獲得したことで、これらの鳥類の繁栄に貢献してきたことを示した。
    本研究では、同じく糖を豊富に含む果実を主食とするマイコドリ科鳥類を対象に解析を行う。マイコドリは、オスのアクロバティックな求愛ダンスが性淘汰の例としてよく知られるが、高栄養価である果実を食糧源として利用できたことが、多くの運動量を要する求愛行動の進化を促したと考えられている。そこで、今回新たに解読したマイコドリのゲノム配列を元に、旨味受容体や小腸二糖分解酵素の機能を調べ、味覚や消化機能が果実食性獲得にどう貢献してきたかを明らかにする。
    本年度は、昨年度に作製した旨味受容体（T1R1及びT1R3）の培養細胞発現用プラスミドを用いて機能解析を行った。また祖先型受容体の配列推定と機能解析を行い、祖先での糖受容能の有無を明らかにした。

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  • 脊椎動物における味覚受容体TAS1Rの新規レパートリーの機能解明

    Grant number：19H03272  2019.4 - 2022.3

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    西原 秀典, 石丸 喜朗, 戸田 安香

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    Grant amount：\17030000 （ Direct Cost: \13100000 、 Indirect Cost：\3930000 ）

    本研究では顎口類の共通祖先においてTAS1R遺伝子がどのようなプロセスで多様化し、また現在の各生物種に至るまでどのような配列進化と機能進化を遂げてきたのかを解明することが目的である。今年度は機能解析のための基盤情報を揃えるため、複数の脊椎動物種について機能解析のための全遺伝子レパートリーの配列情報の収集をおこなった。アホロートルに関しては既知のゲノムおよびトランスクリプトームの一次データから独自にアセンブルをおこない、全レパートリーのほぼ完全長を決定した。肺魚に関しても既知のトランスクリプトームデータの再アセンブルにより新規TAS1R遺伝子を可能な限り再構築した。また一部の生物種については予定通りクローニングを進めており、培養細胞を用いたリガンド特定のために実験を開始することができている。ただし機能の検出が十分にできなかった遺伝子もあり、それについては今後実験条件を検討し改善する必要がある。また発現解析についてもプローブの作製が完了し順調に進行中である。これら機能解析と発現解析は次年度以降も予定通り継続する。さらに本研究の発展のために新規クレードを保有する生物種を可能な限り多く特定し、各系統におけるTAS1R遺伝子の重複と消失を含めた包括的進化史を正確に明らかにすることが不可欠である。そのために数十種の脊椎動物のゲノム情報に基づいて全TAS1Rを同定し、その遺伝子ファミリーの多様性の全体像を掴むべく研究を進める予定である。

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  • Elucidation of intestinal tuft cell-expressed receptor function in type 2 innate immunity and its application to food science

    Grant number：19H02915  2019.4 - 2022.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Ishimaru Yoshiro

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    Grant amount：\16510000 （ Direct Cost: \12700000 、 Indirect Cost：\3810000 ）

    Using transgenic mice for in vivo live imaging in which intestinal tuft cells detecting helminths are fluorescent-labeled, we detected responses to succinic acid, salicin, and nematode excretory/secretory product in tuft cells or their surrounding cells. When succinic acid was administered, the number of type 2 innate lymphoid cells present in intestinal lamina propria was larger in tuft cell-localized Gprc5c knockout mice than in wild-type mice, suggesting that Gprc5c may suppress type 2 innate immune response during inflammation.

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  • 鳥類をモデルとした食性の多様化と味覚受容体の機能との関連

    2018.10 - 2021.3

    文部科学省  科学研究費補助金（国際共同研究加速基金(国際共同研究強化(B))） 

    石丸 喜朗

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    Authorship：Principal investigator  Grant type：Competitive

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  • 小腸刷子細胞に発現する受容体の生理機能の解明と阻害物質の探索

    2016.4 - 2019.3

    文部科学省  科学研究費補助金（基盤研究(B)） 

    石丸 喜朗

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    Authorship：Principal investigator  Grant type：Competitive

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  • Obesity induced by collapsed feeding rhythm

    Grant number：16K12746  2016.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    OIKE Hideaki, ISHIMARU Yoshiro, OISHI Katsutaka

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    Grant amount：\3510000 （ Direct Cost: \2700000 、 Indirect Cost：\810000 ）

    In this study, we analyzed effects of light/dark- or feeding/fasting- pattern on body weight, energy metabolism, and circadian clocks of peripheral tissues in mice. As a result, periodic advance of light/dark cycle efficiently increased body weight gain. Under this light/dark condition, the body weight gain was correlated with decrease of circadian amplitude of respiratory quotient fluctuation and also correlated with glucose usage. It was suggested that collapse of circadian feeding rhythm due to irregular activity pattern caused suppression of lipid usage, leading to obesity.

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  • Investing the Mechanism of Salty Taste Reception and Response

    Grant number：15K12334  2015.4 - 2017.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    ABE Keiko, ISHIMARU Yoshiro

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    Grant amount：\3640000 （ Direct Cost: \2800000 、 Indirect Cost：\840000 ）

    The present study aims to develop some salt taste-enhancing compounds. We constructed Skn-1a knocked-out mice (S-KO mice) in which sweet, bitter and umami taste recepting cells disappeared and sour taste recepting cell activity was enhanced 3 times. The RNA-seq analysis of this mouse made us find several copies of a candidate ion channel expressed specifically in Type I cells. These genes included an ion channel (X-channel) which stained the taste buds of S-KO mice. This channel was expressed in humans as well. Also, this X-channel was a sodium channel. To know the physiological property of this channel, this was introduced into HEK 293 cell, which was then submitted to electrophisical experiment. However, the HEK 293 cell did not respond to sodium ion. This proposes the possibility that the cell is associated with the transport of some other ions. To analyze the phenotype of X-channel, we constructed the KO mice to design the target sequence.

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  • Peripheral Response to Tastant Signals and Central Cognition for Analysis of Their Coordination and its Application to the Science of Food for Life

    Grant number：26242007  2014.4 - 2017.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    Abe Keiko, ASAKURA Tomiko, MISAKA Takumi, ISHIMARU Yoshiro

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    Grant amount：\43810000 （ Direct Cost: \33700000 、 Indirect Cost：\10110000 ）

    We constructed Skn-1a knocked-out (S-KO) mice and found the absence of this transcription factor in the gut. The S-KO mice and wild type (WT) mice were similar in diet intake, but the former mice were distinctly lower than the latter mice in terms of body weight. While there was no difference in lipid absorption between S-KO and WT mice, the S-KO mice were characterized by a larger degree of obesity suppression at the age of 16 weeks. The S-KO mice were also characterized by the activation of hyperpressure and gastrocnemius mitochondrial copy number. Also, an oral glucose charge test showed that there was no blood glucose level difference between S-KO and WT mice, the former mice had a larger insulin secretion. This means that the lower body weight observed for S-KO mice is due to catecholamine-induced activation of lipolysis.

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  • 酸味・塩味受容機構の全容解明に向けた新規イオンチャネル型味覚受容体の探索

    2014.4 - 2016.3

    文部科学省  科学研究費補助金（挑戦的萌芽研究 ） 

    石丸 喜朗

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    Authorship：Principal investigator  Grant type：Competitive

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  • 消化管における味覚関連遺伝子発現細胞の機能解析

    2013.4 - 2016.3

    文部科学省  科学研究費補助金（基盤研究(B)） 

    石丸 喜朗

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    Authorship：Principal investigator  Grant type：Competitive

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  • Characterization of sweet taste receiving cells in the gut and analysis of their cellular functions

    Grant number：25560046  2013.4 - 2015.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    ABE Keiko, ISHIMARU Yoshiro

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    Grant amount：\3770000 （ Direct Cost: \2900000 、 Indirect Cost：\870000 ）

    The transcription factor Skn-1a was found to be expressed not only in taste cells but also in gut brush cells. Also, it was involved in their differentiation. Mice with deleted Skn-1a (S-KO) and wild type mice showed similar food intakes when fed on a standard diet (AIN 93G) and on a high-fat diet. Despite that, S-KO mice were significantly different from wild type mice is terms of body weight decrease, body fat reduction, insulin secretion decrease at the time of OGTT, serum ketone body elevation, and so on. This indicates that lipid metabolism is more activated in Skn-1a mice and also that their brush border cells function possibly as an energy sensor.

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  • Elucidation of the effect of polyphenols on the inhibition of intestinal cholesterol transport and for their clinical applications

    Grant number：24500969  2012.4 - 2015.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    KOBAYASHI Shoko, ISHIMARU Yoshiro

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    Grant amount：\5200000 （ Direct Cost: \4000000 、 Indirect Cost：\1200000 ）

    Niemann-pick C1-Like 1 (NPC1L1) mediates cholesterol absorption, and ezetimibe is a potent NPC1L1 inhibitor applicable for medication of hypercholesterolemia. Epidemiological studies demonstrated that consumption of polyphenols correlates with a decreased risk for atherosclerosis, and we hypothesized that polyphenols inhibit intestinal transport of cholesterol. We elucidated the kinetic parameters of intestinal cholesterol absorption using Caco-2 cells and screened 34 polyphenols. Luteolin and quercetin inhibited cholesterol absorption by Caco-2 cells and human embryonic kidney 293T cells expressing NPC1L1. Serum cholesterol levels significantly decreased more in rats fed both cholesterol and luteolin (or quercetin), than in those observed in the cholesterol feeding group. These results suggest that luteolin and quercetin reduce high blood cholesterol levels by specifically inhibiting intestinal cholesterol absorption mediated by NPC1L1.

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  • Integrated molecular analysis of taste signal generation, transmission and cognition

    Grant number：23248058  2011.4 - 2014.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    ABE Keiko, AIZAWA Hiroyuki, ISHIMARU Yoshiro, OKADA Shinji

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    Grant amount：\50830000 （ Direct Cost: \39100000 、 Indirect Cost：\11730000 ）

    Outline of the research: For the integrated analysis of taste systems, (1) we found the target genes AnoI, Kene3, Sec61a1 that are involved in construction of electric potential of saltiness reception (type I) cell membrane; (2) PLC-beta2-WGA medaka fish analysis led to comprehensive elucidation of the taste transmission pathway from bitterness/amino acid receiving cells to the endbrain and the visualization of saltiness-receiving cell to the NST taste area in PKD1L3-WGA mice was successive; and (3) integrated expression markers in weaning mice, SNAP25, EGr-2 and Krox-20, were distinctly activated its signal in the taste area when the mice were given a solid food at the stage of weaning in comparison with the case that they were still given a liquid food. (4) we also showed that there is a relationship between the tastant quality in diet and the food intake.

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  • 味覚情報伝達神経回路の可視化と形成維持機構の解明

    2010.4 - 2013.3

    文部科学省  科学研究費補助金（若手研究(A)） 

    石丸 喜朗

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    Authorship：Principal investigator  Grant type：Competitive

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  • 酸味受容体候補の生理機能の検証と食品科学的応用に向けた分子基盤の解明

    2008.4 - 2010.3

    文部科学省  科学研究費補助金（若手研究(B)） 

    石丸 喜朗

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    Authorship：Principal investigator  Grant type：Competitive

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  • 酸味受容体候補PKD1L3/PKD2L1の分子細胞生物学的解析

    2007.4 - 2008.3

    文部科学省  科学研究費補助金(若手研究（スタートアップ）） 

    石丸 喜朗

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    Authorship：Principal investigator  Grant type：Competitive

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  • TRP channel members, PKD1L3 and PKD2L1, in sour taste sensation

    Grant-in-Aid for Scientific Research 

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    Grant type：Competitive

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Teaching Experience

  • 食品機能化学特論

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  • 食品機能化学

    Institution：明治大学

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  • 動物資源化学

    Institution：明治大学

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  • 生化学Ⅰ

    Institution：明治大学

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  • バイオテクノロジー論

    Institution：跡見学園女子大学

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  • 現代生命科学Ⅰ

    Institution：東京大学

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  • 全学自由ゼミナール

    Institution：東京大学

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