Physiological function of the receptor expressing intestinal tuft cells and screening of its inhibitors

• Project/Area Number: 16H04919
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Food science
• Research Institution: Meiji University
• Principal Investigator: Ishimaru Yoshiro 明治大学, 農学部, 専任准教授 (10451840)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2016: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
• Keywords: 受容体 / 刷子細胞 / 代謝 / 免疫 / 遺伝子破壊マウス / 消化管

Outline of Final Research Achievements

To elucidate the function of the orphan receptor Gprc5c, which is expressed in intestinal tuft cells, in vivo, we generated its knockout mice by new genome editing methods, TALEN and CRISPER/Cas9 and analyzed its phenotypes. KO mice have reduced body weight. Infection experiments showed that Gprc5c may not be involved in type 2 innate immune response against nematode, Nippostrongylus brasiliensis, infection.

Academic Significance and Societal Importance of the Research Achievements

近年、アレルギー性疾患やメタボリックシンドロームは解決すべき重要な社会問題になっている。小腸刷子細胞の頂端部に局在するオーファン受容体の生理機能が解明され、この受容体を阻害する食品由来因子などの化合物を見つけることができれば、アレルギー性疾患や肥満・糖尿病の予防や治療に繋げることが期待される。

Research Products

• [Journal Article] Positive/Negative Allosteric Modulation Switching in an Umami Taste Receptor (T1R1/T1R3) by a Natural Flavor Compound, Methional. (2018)
  • Author(s): Toda Y, Nakagita T, Hirokawa T, Yamashita Y, Nakajima A, Narukawa M, Ishimaru Y, Uchida R, Misaka T.
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 11796-11796
  • DOI: 10.1038/s41598-018-30315-x
  • NAID: 120006546000
  • Peer Reviewed / Open Access
• [Journal Article] Gene Expression Analysis of the Effect of Ischemic Infarction in Whole Blood (2017)
  • Author(s): Takuma Ayako、Abe Arata、Saito Yoshikazu、Nito Chikako、Ueda Masayuki、Ishimaru Yoshiro、Harada Hideki、Abe Keiko、Kimura Kazumi、Asakura Tomiko
  • Journal Title: International Journal of Molecular Sciences Volume: 18 Issue: 11 Pages: 2335-2335
  • DOI: 10.3390/ijms18112335
  • Peer Reviewed / Open Access
• [Journal Article] 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 (2017)
  • Author(s): Maeda N, Narukawa M, Ishimaru Y, Yamamoto K, Misaka T and Abe K
  • Journal Title: Neuroscience Letters Volume: 印刷中 Pages: 53-58
  • DOI: 10.1016/j.neulet.2017.03.046
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Expanding frontiers in weight-control research explored by young investigators. (2017)
  • Author(s): Ishimaru Y, Kozuka C, Nakajima K, and Sasaki T
  • Journal Title: J. Physiol. Sci. Volume: 67 Issue: 1 Pages: 83-95
  • DOI: 10.1007/s12576-016-0495-7
  • NAID: 40021064558
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Olfactory receptor accessory proteins play crucial roles in receptor function and gene choice (2017)
  • Author(s): R. Sharma, Y. Ishimaru, I. Davison, K. Ikegami, M. S. Chien, H. You, Q. Chi, M. Kubota, M. Yohda, M. Ehlers, H. Matsunami
  • Journal Title: Elife Volume: 印刷中
  • DOI: 10.7554/elife.21895
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Catecholamines facilitate fuel expenditure and protect against obesity via a novel network of the gut-brain axis in transcription factor Skn-1-deficient mice. (2016)
  • Author(s): Ushiama, S., Ishimaru, Y., Narukawa, M., Yoshioka, M., Kozuka, C., Watanabe, N., Tsunoda, M., Osakabe, N., Asakura, T., Masuzaki, H., and Abe, K.
  • Journal Title: EBioMedicine Volume: 8 Pages: 60-71
  • DOI: 10.1016/j.ebiom.2016.04.031
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Variation in ligand responses of the bitter taste receptors TAS2R1 and TAS2R4 among New World monkeys. (2016)
  • Author(s): K. Tsutsui, M. Otoh, K. Sakurai, N. Suzuki-Hashido, T. Hayakawa, T. Misaka, Y. Ishimaru, F. Aureli, A. D. Melin, *S. Kawamura, *H. Imai.
  • Journal Title: BMC Evolutionary Biology Volume: 16 Issue: 1 Pages: 208-208
  • DOI: 10.1186/s12862-016-0783-0
  • NAID: 120006223634
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Spontaneous Bilateral Cervical Internal Carotid and Vertebral Artery Dissection in a Japanese Patient without Collagen Vascular Disease with Special Reference to Single-Nucleotide Polymorphisms (2016)
  • Author(s): Abe Arata、Nito Chikako、Sakamoto Yuki、Nogami Akane、Hokama Hiroyuki、Takahashi Shiro、Kirita Kumiko、Ueda Masayuki、Ishimaru Yoshiro、Kimura Kazumi
  • Journal Title: Journal of Stroke and Cerebrovascular Diseases Volume: 25 Issue: 8 Pages: e114-e117
  • DOI: 10.1016/j.jstrokecerebrovasdis.2016.04.027
  • Peer Reviewed
• [Journal Article] Amino acid residues of bitter taste receptor TAS2R16 that determine sensitivity in primates to β-glycosides (2016)
  • Author(s): Imai Hiroo, Suzuki-Hashido Nami, Ishimaru Yoshiro, Takanobu Sakurai, Lijie Yin, Wenshi Pan, Masaji Ishiguro, Masuda Katsuyoshi, Abe Keiko, Misaka Takumi, Hirai Hirohisa
  • Journal Title: Biophysics and Physicobiology Volume: 13 Issue: 0 Pages: 165-171
  • DOI: 10.2142/biophysico.13.0_165
  • NAID: 130005165371
  • ISSN: 2189-4779
  • Peer Reviewed
• [Presentation] コイ味覚受容体の発現解析 (2019)
  • Author(s): 久保園 峻、戸田 安香、石丸 喜朗
  • Organizer: 日本農芸化学会2019年度大会
• [Presentation] 霊長類T1R1/T1R3におけるグルタミン酸受容能獲得の分子基盤：クモザルに注目した検討 (2019)
  • Author(s): 戸田 安香、早川 卓志、中北 智哉、河村 正二、今井 啓雄、石丸 喜朗、三坂 巧
  • Organizer: 日本農芸化学会2019年度大会
• [Presentation] 小腸刷子細胞頂端部に局在する受容体の生体内機能の検証 (2018)
  • Author(s): 石丸 喜朗
  • Organizer: 日本味と匂学会第52回大会
  • Invited
• [Presentation] 脊椎動物における味覚受容体T1Rファミリーの進化解析 (2018)
  • Author(s): 西原 秀典、戸田 安香、工楽 樹洋、蔵本 多恵、岡部 正隆、石丸 喜朗
  • Organizer: 日本進化学会第20回大会
• [Presentation] 小腸刷子細胞頂端部に局在する受容体の生体内機能の検証 (2017)
  • Author(s): 谷下道大, 成川真隆, 戸田安香, 石渡賢治, 吉岡美紗子, 朝倉富子, 嘉糠洋陸, 益崎裕章, 阿部啓子, 石丸喜朗
  • Organizer: 第71回日本栄養・食糧学会大会
• [Presentation] 霊長類における旨味受容体の機能解析 (2017)
  • Author(s): 戸田安香, 石丸喜朗
  • Organizer: 日本味と匂学会第51回大会
• [Presentation] Intestinal tuft cells: immunity and metabolism (2017)
  • Author(s): Yoshiro Ishimaru
  • Organizer: The 16th International Symposium on Molecular and Neural Mechanisms of Taste and Olfactory Perception
  • Int'l Joint Research
• [Presentation] 小腸刷子細胞に発現する遺伝子の生体内機能の検証 (2017)
  • Author(s): 谷下 道大、成川 真隆、石渡 賢治、吉岡 美紗子、朝倉 富子、嘉糠 洋陸、阿部 啓子、石丸 喜朗
  • Organizer: 日本農芸化学会2017年度京都大会
• [Presentation] Catecholamines Facilitate Fuel Expenditure and Protect Against Obesity via a Novel Network of the Gut-Brain Axis in Transcription Factor Skn-1 -deficient Mice (2016)
  • Author(s): Ishimaru Yoshiro、Ushiama Shota、Narukawa Masataka、Yoshioka Misako、Kozuka Chisayo、Watanabe Naoki、Tsunoda Makoto、Osakabe Naomi、Asakura Tomiko、Masuzaki Hiroaki、Abe Keiko
  • Organizer: ISOT2016
  • Int'l Joint Research
• [Book] アレルギー性疾患や寄生虫感染と刷子細胞 (2019)
  • Author(s): 石丸 喜朗
  • Total Pages: 5
  • Publisher: 医歯薬出版
• [Book] 味覚と味覚受容体 (2018)
  • Author(s): 石丸 喜朗
  • Total Pages: 5
  • Publisher: 医歯薬出版
• [Book] さまざまな脊椎動物における味覚の進化 (2018)
  • Author(s): 戸田 安香、石丸 喜朗
  • Total Pages: 5
  • Publisher: 医歯薬出版
• [Book] アグリバイオ 2017年8月臨時増刊号 (2017)
  • Author(s): 阿部 啓子・中嶋 康博
  • Total Pages: 100
  • Publisher: 北隆館
• [Book] おいしさの科学的評価・測定法と応用展開 (2016)
  • Author(s): 阿部啓子、石丸喜朗
  • Total Pages: 212
  • Publisher: シーエムシー出版
  • ISBN: 9784781311777
• [Remarks] 腸脳軸を介した新しいエネルギー代謝調節機構を解明
  • URL: http://www.a.u-tokyo.ac.jp/topics/2016/20160531-1.html