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Artificial activation of Ca2+ channel subtypes by chemical biology approach

Research Project

Project/Area Number 25282238
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Chemical biology
Research InstitutionKyoto University

Principal Investigator

KIYONAKA Shigeki  京都大学, 地球環境学堂, 准教授 (90422980)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2013: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
KeywordsCa2+チャネル / グルタミン酸受容体 / AMPA受容体 / サブタイプ / ケミカルバイオロジー / 活性化 / イオンチャネル
Outline of Final Research Achievements

In central nervous systems, excitatory neurotransmission is essential for our memory and learning. Glutamate, a typical excitatory neurotransmitter in animals, is recognized by glutamate receptors in synapses. Glutamate receptors are categorized into ionotropic- or metabotropic-types. These are composed of 25 subtypes, each of which has essential roles in neurotransmission and synaptic plasticity, a putative molecular mechanism of our memory. For subtype-selective activation of glutamate receptors, we here developed a novel method for selective activation of the receptor subtypes using genetic manipulation and coordination chemistry,. In this method, we introduced two His mutations in the vicinity of the ligand binding pockets in glutamate receptors. These His mutations acted as an allosteric site upon complexation with a Pd complex in a bidentate coordination fashion to stabilize the active conformation of the ligand binding pockets.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (18 results)

All 2016 2015 2014 2013 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (13 results) (of which Invited: 2 results)

  • [Journal Article] Validating subcellular thermal changes revealed by fluorescent thermosensors2015

    • Author(s)
      Kiyonaka S, Sakaguchi R, Hamachi I, Morii T, Yoshizaki T, Mori Y
    • Journal Title

      Nature Method.

      Volume: 12 Issue: 9 Pages: 801-802

    • DOI

      10.1038/nmeth.3548

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Live Cell Off-target Identification of Lapatinib Using Ligand-Directed Tosyl Chemistry.2014

    • Author(s)
      Yamaura K, Kuwata K, Tamura T, Kioi Y, Takaoka Y, Kiyonaka S, Hamachi I.
    • Journal Title

      Chem. Commun.

      Volume: 50 Issue: 91 Pages: 14097-14100

    • DOI

      10.1039/c4cc05885b

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LDAI-Based Chemical Labeling of Intact Membrane Proteins and Its Pulse-Chase Analysis under Live Cell Conditions2014

    • Author(s)
      Takayuki Miki, Sho-hei Fujishima, Kazuhiro Komatsu, Keiko Kuwata, Shigeki Kiyonaka, Itaru Hamachi
    • Journal Title

      Chemistry & Biology (Cell press)

      Volume: 21 Issue: 8 Pages: 1013-1022

    • DOI

      10.1016/j.chembiol.2014.07.013

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Transnitrosylation directs TRPA1 selectivity in N-nitrosamine activators.2014

    • Author(s)
      Kozai D, Kabasawa Y, Ebert M, Kiyonaka S ; Finnan, Otani Y, Numata T, Takahashi N, Mori Y, Ohwada T.
    • Journal Title

      Molecular Pharmacology

      Volume: 85 Issue: 1 Pages: 175-185

    • DOI

      10.1124/mol.113.088864

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetically encoded fluorescent thermosensors visualize subcellular thermoregulation in living cells2013

    • Author(s)
      Shigeki Kiyonaka, Taketoshi Kajimoto, Reiko Sakaguchi, Daisuke Shinmi, Mariko Omatsu-Kanbe, Hiroshi Matsuura, Hiromi Imamura, Takenao Yoshizaki, Itaru Hamachi, Takashi Morii, Yasuo Mori
    • Journal Title

      Nature Methods

      Volume: 10 Issue: 12 Pages: 1232-1238

    • DOI

      10.1038/nmeth.2690

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Neuro Chemical Biology: chemical approaches for visualization or activation of neurotransmitter receptors2016

    • Author(s)
      Shigeki Kiyonaka
    • Organizer
      日本化学会第96春季年会 (同志社大学・京田辺キャンパス) 3/24-27
    • Place of Presentation
      同志社大学(京都府、京田辺市)
    • Year and Date
      2016-03-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] 神経細胞におけるグルタミン酸受容体の可視化と活性制御の新手法2016

    • Author(s)
      清中 茂樹
    • Organizer
      「分子ロボティクス研究会」2016年1月定例研究会
    • Place of Presentation
      京都大学(京都府、京都市)
    • Year and Date
      2016-01-23
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Visualization of Native AMPA Receptors in Central Nervous Systems Using a Novel Chemical Labeling Technique2015

    • Author(s)
      Shigeki Kiyonaka, Sho Wakayama, Michisuke Yuzaki, Itaru Hamachi
    • Organizer
      BMB2015(第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会)
    • Place of Presentation
      神戸国際会議場(兵庫県、神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] On-cell Coordination Chemistry (OcCC)によるグルタミン酸受容体の選択的活性化2015

    • Author(s)
      窪田 亮、清中 茂樹、浜地 格
    • Organizer
      第9回バイオ関連化学シンポジウム
    • Place of Presentation
      熊本大学(熊本県、熊本市)
    • Year and Date
      2015-09-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] Chemical Biology of Neuronal Synapses(1):Dynamics of the ionotropic glutamate receptors endogenously expressed in neurons2015

    • Author(s)
      Shigeki Kiyonaka, Sho Wakayama, Kazuhiro Komatsu, Itaru Hamachi
    • Organizer
      日本化学会第95春季年会
    • Place of Presentation
      日本大学(千葉県、船橋市)
    • Year and Date
      2015-03-26 – 2015-03-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] 神経シナプスのケミカルバイオロジー研究2015

    • Author(s)
      清中 茂樹
    • Organizer
      第17回生命化学研究会
    • Place of Presentation
      三翠園(高知県、高知市)
    • Year and Date
      2015-01-08 – 2015-01-09
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 神経細胞内在性AMPA受容体の特異的ケミカルラベルとライブイメージングへの展開2014

    • Author(s)
      若山 翔、清中 茂樹、松田 信爾、柚崎 通介、浜地 格
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都国際会館(京都府、京都市)
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 神経化学生物学(1):LDAI化学によるAMPA型グルタミン酸受容体(AMPAR)のケミカルラベル化戦略

    • Author(s)
      清中 茂樹・若山 翔・松田 信爾・柚﨑 道介・浜地 格
    • Organizer
      日本化学会第94春季年会
    • Place of Presentation
      名古屋大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] 神経化学生物学(2) : 神経細胞シナプスAMPARの蛍光ラベル化

    • Author(s)
      森川 祐真・若山 翔・清中 茂樹・浜地 格
    • Organizer
      日本化学会第94春季年会
    • Place of Presentation
      名古屋大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] 神経化学生物学(3) ラベル化AMPARによるリガンドセンシング

    • Author(s)
      若山 翔・清中 茂樹・浜地 格
    • Organizer
      日本化学会第94春季年会
    • Place of Presentation
      名古屋大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] 神経化学生物学 (4) : AGD化学によるAMPAR複合体のケミカルラベリング

    • Author(s)
      道籏友紀子・若山 翔・清中 茂樹・浜地 格
    • Organizer
      日本化学会第94春季年会
    • Place of Presentation
      名古屋大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] 神経化学生物学(5):神経伝達物質受容体の機能解析を指向したNMDA受容体のケミカルラベル

    • Author(s)
      小松 和弘・清中 茂樹・浜地 格
    • Organizer
      日本化学会第94春季年会
    • Place of Presentation
      名古屋大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] 神経化学生物学(6):細胞表層配位化学によるAMPARの活性制御

    • Author(s)
      窪田 亮・清中 茂樹・浜地 格
    • Organizer
      日本化学会第94春季年会
    • Place of Presentation
      名古屋大学
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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