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Analysis of molecules involved in exocytosis with dual FRET and fluorescent lifetime imaging

Research Project

Project/Area Number 17K08530
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General physiology
Research InstitutionKitasato University

Principal Investigator

Takahashi Noriko  北里大学, 医学部, 教授 (60332178)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords神経伝達物質 / 分泌 / 糖尿病 / インスリン / 膜融合 / レーザー顕微鏡 / 2光子励起 / シナプス / 内分泌細胞 / 蛍光 / 共焦点顕微鏡 / SNARE / 浸透圧 / 生理学 / 神経細胞 / 分泌機構 / 神経伝達機構 / 蛍光技術 / 顕微鏡 / 蛍光寿命画像 / 2光子顕微鏡 / 蛍光共鳴エネルギー移動 / 神経シナプス / PKA / 生体分子 / 画像 / 蛋白質
Outline of Final Research Achievements

We investigated the mechanism of neurotransmitter release, which is involved in cognitive function, and mechanism of insulin release, which is related to the pathogenesis of diabetes mellitus. We mainly focused in the final step of secretion, exocytosis, as well as granule movement. Various molecules involved in exocytosis were labeled with fluorescent probes, and we analyzed their dynamics and assembly utilizing fluorescent resonance energy transfer and fluorescent lifetime imaging system, in two-photon excitation system. In some species of the cells, the mechanical stress, osmotic pressure, regulated the release probability.

Academic Significance and Societal Importance of the Research Achievements

脳における神経伝達物質の放出は、人としての機能に深くかかわる事象である。また、糖尿病はわが国をはじめ、アジアならびに世界において患者数が漸増傾向にある疾患であるが、その成因に深くかかわる現象としてインスリン分泌が挙げられる。我々はこれらの現象が細胞レベルでいかに起こり、環境や状況に応じて調節されているか解明した。立ち上げた実験系は、遺伝子工学的手法を用いた分子の蛍光標識、および細胞内微細環境の実時間画像化など最先端解析手法の特徴を生かしたもので、他の細胞における研究にも応用できる汎用性の高い手法である。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (27 results)

All 2020 2019 2018 2017 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (18 results) (of which Int'l Joint Research: 8 results,  Invited: 6 results) Remarks (4 results)

  • [Journal Article] インスリン分泌のダイナミクス2020

    • Author(s)
      高橋倫子
    • Journal Title

      糖尿病・内分泌代謝科

      Volume: 50 Pages: 71-76

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Bidirectional in vivo structural dendritic spine plasticity revealed by two-photon glutamate uncaging in the mouse neocortex.2019

    • Author(s)
      Noguchi J, Nagaoka A, Hayama T, Ucar H, Yagishita S, Takahashi N, Kasai H.
    • Journal Title

      Scientific Reports.

      Volume: 9 Issue: 1 Pages: 13922-13922

    • DOI

      10.1038/s41598-019-50445-0

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Strong stimulation triggers full fusion exocytosis and very slow endocytosis of the small dense core granules in carotid glomus cells.2018

    • Author(s)
      Tse A, Lee AK, Takahashi N, Gong A, Kasai H, Tse FW.
    • Journal Title

      J Neurogenet

      Volume: 32 Issue: 3 Pages: 267-278

    • DOI

      10.1080/01677063.2018.1497629

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] In Vivo Volume Dynamics of Dendritic Spines in the Neocortex of Wild-Type and Fmr1 KO Mice.2018

    • Author(s)
      Ishii K, Nagaoka A, Kishida Y, Okazaki H, Yagishita S, Ucar H, Takahashi N, Saito N, Kasai H.
    • Journal Title

      eNeuro

      Volume: 5 Issue: 5 Pages: 1-13

    • DOI

      10.1523/eneuro.0282-18.2018

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] エクソサイトーシスの分子機構2018

    • Author(s)
      高橋倫子
    • Journal Title

      生体の科学

      Volume: 69 Pages: 227-232

    • Related Report
      2018 Research-status Report
  • [Presentation] Mechanosensing of the enlargement of dendritic spines by presynaptic terminals in rat hippocampus.2020

    • Author(s)
      Ucar Hasan、渡辺惠、野口潤、柳下祥、守本祐一、高橋倫子、河西春郎
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Renal tissue kallikrein may be involved in the regulatory Ca transport along the kidney distal nephron2020

    • Author(s)
      Yukiko Yasuoka, Tomomi Oshima, Yuichi Sato, Noriko Takahashi, Hiroshi Nonoguchi, Katsumasa Kawahara
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 膵β細胞制御におけるMek/Erkシグナルの役割の解明2019

    • Author(s)
      生島芳子、小林直樹、粟澤元晴、諏訪内浩紹、添田光太郎、村谷匡史、高橋倫子、 植木浩二郎
    • Organizer
      第62回日本糖尿病学会年次学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 基礎医学から糖尿病学へのアプローチ2019

    • Author(s)
      高橋倫子
    • Organizer
      日本糖尿病学会関東甲信越支部主催 Young Diabetologists Research Forum
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Imaging secretory cells and molecular configurations of exocytic proteins.2019

    • Author(s)
      Noriko Takahashi, Hiroyasu Hatakeyama, Tomomi Oshima, Yuichi Morimoto, Haruo Kasai.
    • Organizer
      FAOPS 2019 (The 9th Federation of Asian and Oceanian Physiological Societies Congress)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mechanical forces of spine enlargement detected by presynaptic FRET/FLIM imaging.2019

    • Author(s)
      Haruo Kasai, Hasan Ucar, Jun Noguchi, Satoshi Watanabe, Sho Yagishita, Noriko Takahashi.
    • Organizer
      FAOPS 2019 (The 9th Federation of Asian and Oceanian Physiological Societies Congress)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Low-Pi diet-induced metabolic acidosis with alkalinuria was reversed in the Pendrin KO mice.2019

    • Author(s)
      Yukiko Yasuoka, Tomomi Oshima, Yuichi Sato, Hiroshi Nonoguchi, Noriko Takahashi, Katsumasa Kawahara.
    • Organizer
      FAOPS 2019 (The 9th Federation of Asian and Oceanian Physiological Societies Congress)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Characterizations of the HCO3- transport activities of a choroid plexus-specific variant of NBC4.2019

    • Author(s)
      Hidekazu Fukuda, Noriko Takahashi.
    • Organizer
      FAOPS 2019 (The 9th Federation of Asian and Oceanian Physiological Societies Congress)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 蛍光技術を活用した生理活性物質放出機構の解析2018

    • Author(s)
      高橋倫子 守本祐一 河西春郎
    • Organizer
      第61回日本糖尿病学会年次学術集会 シンポジウム
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Molecular configuration for primed exocytosis analyzed with 2-photon FLIM.2018

    • Author(s)
      Noriko Takahashi.
    • Organizer
      Forefront of Neurotransmitter Release and Calcium Channel Signaling-A Symposium in honor of Sumiko Mochida
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Fludrocortisone stimulates erythropoietin (Epo) protein expression in the distal tubules of mouse kidney.2018

    • Author(s)
      Yukiko Yasuoka, Tomomi Oshima, Yuichiro Izumi, Yuichi Sato, Noriko Takahashi, Hiroshi Nonoguchi, Katsumasa Kawahara.
    • Organizer
      American Society of Nephrology 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Production and release of the erythropoietin (Epo) protein by the severe hypoxia.2018

    • Author(s)
      Yukiko Yasuoka, Tomomi Oshima, Yuichiro Izumi, Yuichi Sato, Noriko Takahashi, Hiroshi Nonoguchi, Katsumasa Kawahara.
    • Organizer
      American Society of Nephrology 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Potentiation of presynaptic functions by mechanical forces generated by spine enlargement.2018

    • Author(s)
      Hasan Ucar, Satoshi Watanabe, Jun Noguchi, ShoYagishita, Yuichiro Morimoto, Noriko Takahashi, Haruo Kasai.
    • Organizer
      Annual Meeting of Society of Neuroscience 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 蛍光技術と2光子顕微鏡を活用した開口放出機構の解析2018

    • Author(s)
      守本祐一, 澤田和可子, 河西春郎, 高橋倫子
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 腎皮質集合管の B 型間在細胞(側底膜)に局在する Ca 感知受容体の役割2018

    • Author(s)
      大嶋 友美, 安岡 有紀子, 福田 英一, 高橋 倫子, 河原 克雅
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 基礎医学から広がる糖尿病学2017

    • Author(s)
      高橋倫子
    • Organizer
      第60回糖尿病学会年次学術集会 シンポジウム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 画像化手法を用いた膵内分泌研究2017

    • Author(s)
      高橋倫子
    • Organizer
      第44回日本神経内分泌学会学術集会 シンポジウム「神経内分泌研究に役立つ生理研究手法」
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Configuration of SNARE proteins and calcium-dependent exocytosis2017

    • Author(s)
      Yuichi Morimoto, Wakako Sawada , Haruo Kasai, Noriko Takahashi
    • Organizer
      20th International Symposium on calcium binding proteins and calcium function in health and disease (CaBP2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Remarks] 北里大学生理学

    • URL

      https://www.kitasato-u.ac.jp/med/research/departments/medicine/seiri-kh.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 北里大学医学部生理学(高橋単位)

    • URL

      https://www.kitasato-u.ac.jp/med/research/departments/medicine/seiri-kh.html

    • Related Report
      2018 Research-status Report
  • [Remarks] 蛍光技術を活用した生理活性物質の放出機構の解明 高橋倫子 科研費News 2017年度

    • URL

      http://www.jsps.go.jp/j-grantsinaid/22_letter/data/news_2017_vol3/p17.pdf

    • Related Report
      2017 Research-status Report
  • [Remarks] 生理学(高橋単位) 北里大学医学部

    • URL

      https://www.kitasato-u.ac.jp/med/research/departments/medicine/seiri-kh.html

    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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