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Elucidation of regulatory mechanisms of type 2 ryanodine receptors by introducing artificial amino acids

Research Project

Project/Area Number 24590330
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General pharmacology
Research InstitutionJuntendo University

Principal Investigator

MURAYAMA Takashi  順天堂大学, 医学部, 准教授 (10230012)

Co-Investigator(Renkei-kenkyūsha) KUREBAYASHI Nagomi  順天堂大学, 医学部, 准教授 (50133335)
SAKAMOTO Kensaku  理化学研究所, 拡張遺伝暗号システム研究チーム, チームリーダー (50240685)
OBA Toshiharu  中部大学, 応用生物学部, 教授 (50008330)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsリアノジン受容体 / 筋小胞体 / カルシウムチャネル / 相互作用 / 人工アミノ酸 / 興奮収縮連関 / 不整脈 / S4-S5リンカー
Outline of Final Research Achievements

Type 2 ryanodine receptor is a Ca2+ release channel in the sarcoplasmic reticulum and plays an important role in excitation-contraction coupling in heart. Mutations in RyR2 cause hyperactivate the channel, leading to arrhythmogenic diseases. Here, we examined molecular mechanism of disease-cuasing mutations on the channel activity by determining the properties of the mutant channels. Furthermore, we tried to detect possible interactions within or between subdomains by introducing photo-crosslinkable artificial amino acids. We found that disease-causing mutations affect various parameters of the channel activity. Possible alterations of interactions within the domains are also suggested.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (16 results)

All 2015 2014 2013 2012 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 1 results) Presentation (7 results) Remarks (1 results)

  • [Journal Article] Multifunctional GFP Tag2014

    • Author(s)
      Murayama T, Kobayashi T
    • Journal Title

      Methods Mol Biol

      Volume: 1177 Pages: 151-161

    • DOI

      10.1007/978-1-4939-1034-2_12

    • ISBN
      9781493910335, 9781493910342
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mg2+- and ATP-dependent inhibition of TRPM7 by oxidative stress.2014

    • Author(s)
      Inoue H, Murayama T, Tashiro M, Sakurai T, Konishi M.
    • Journal Title

      Free Radic Biol Med,

      Volume: 72 Pages: 257-266

    • DOI

      10.1016/j.freeradbiomed.2014.04.015

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Usefulness of running wheel for detection of congestive heart failure in dilated cardiomyopathy mouse model2014

    • Author(s)
      Sugihara M, Odagiri F, Suzuki T, Murayama T, Nakazato Y, Unuma K, Yoshida K, Daida H, Sakurai T, Morimoto S, Kurebayashi N.
    • Journal Title

      PLoS One

      Volume: 8(1) Issue: 1 Pages: e55514-e55514

    • DOI

      10.1371/journal.pone.0055514

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Overexpression of ryanodine receptor type 1 enhances mitochondrial fragmentation and Ca2+-induced ATP production in cardiac H9c2 myoblasts2013

    • Author(s)
      O-Uchi J, Jhun BS, Hurst S, Bisetto S, Gross P, Chen M, Kettlewell S, Park J, Oyamada H, Smith GL, Murayama T, Sheu SS
    • Journal Title

      Am J Physiol Heart Circ Physiol

      Volume: 305 Issue: 12 Pages: H1736-H1751

    • DOI

      10.1152/ajpheart.00094.2013

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mitosis-Coupled, Microtubule-Dependent Clustering of Endosomal Vesicles around Centrosomes2013

    • Author(s)
      Takatsu, H., Katoh, Y., Ueda, T., Waguri, S., Murayama, T., Takahashi, S., Shin, H.-W. &Nakayama, K.
    • Journal Title

      Cell Structure and Function

      Volume: 38 Issue: 1 Pages: 31-41

    • DOI

      10.1247/csf.12028

    • NAID

      130004053889

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sperm-associated antigen 4, a novel hypoxia-inducible factor 1 target, regulates eytokinesis, and its expression correlates with the prognosis of renal cell earcinoma.2013

    • Author(s)
      Shoji K, Mimura I, Murayama T, Wada T, Kume H, Goto A, Ohse T, Tanaka T, Inagi R, van der Hoorn FA, Manabe I, Homma Y, Fukayama M, Sakurai T, Hasegawa T, Aburatani H, Kodama T, Nangaku M.
    • Journal Title

      American Journal of Pathology

      Volume: 182 Issue: 6 Pages: 2191-2203

    • DOI

      10.1016/j.ajpath.2013.02.024

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nitric oxide-induced calcium release via ryanodine receptors regulates neuronal function2012

    • Author(s)
      Kakizawa, Sho ; Yamazawa, Toshiko ; Chen, Yili, et al
    • Journal Title

      Embo Journal

      Volume: 31 Issue: 2 Pages: 417

    • DOI

      10.1038/emboj.2011.386

    • URL

      https://localhost/en/publications/c3b06cf2-02ee-43e7-9469-16ff89f843db

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multistep ion channel remodeling and lethal arrhythmia precede heart failure in a mouse model of inherited dilated cardiomyopathy2012

    • Author(s)
      Suzuki T, Shioya T, Murayama T, Sugihara M, Odagiri F, Nakazato Y, Nishizawa H, Chugun A, Sakurai T, Daida H, Morimoto S, Kurebayashi N
    • Journal Title

      PLoS ONE

      Volume: 7 Issue: 4 Pages: e35353-e35353

    • DOI

      10.1371/journal.pone.0035353

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 1型リアノジン受容体チャネルに対する中央領域疾患変異の効果2015

    • Author(s)
      村山 尚、呉林なごみ、山澤徳志子、小山田英人、鈴木純二、金丸和典、小口勝司、飯野正光、櫻井 隆
    • Organizer
      第120回日本解剖学会総会全国学術集会・第92回日本生理学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] 1型リアノジン受容体チャネル活性に対する中央領域疾患変異の効果2015

    • Author(s)
      村山 尚、呉林なごみ、山澤徳志子、小山田英人、鈴木純二、金丸和典、小口勝司、飯野正光、櫻井 隆
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 2型リアノジン受容体の不整脈原性変異はCICR活性とCa2+動態にどのような影響を及ぼすか?2015

    • Author(s)
      呉林なごみ, 村山 尚, 太田亮作, 山下富義, 鈴木純二, 金丸和典, 飯野正光, 櫻井 隆
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-03-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Effects of arrhythmogenic mutations on Ca2+-induced Ca2+ release activities of type 2 ryanodine receptors.2015

    • Author(s)
      Kurebayashi, N., T. Murayama, J. Suzuki, K. Kanemaru, M. Iino, T. Sakurai
    • Organizer
      Biophysical society, 59th Annual Meeting
    • Place of Presentation
      Baltimore
    • Year and Date
      2015-02-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Effects of MH and CCD mutations in the central region on RyR1 channels.2015

    • Author(s)
      Takashi Murayama, Nagomi Kurebayashi, Toshiko Yamazawa, Hideto Oyamada, Junji Suzuki, Kazunori Kanemaru, Katsuji Oguchi, Masamitsu Iino, and Takashi Sakurai
    • Organizer
      Biophysical Society 59th Annual Meeting
    • Place of Presentation
      Baltimore
    • Year and Date
      2015-02-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] 1型リアノジン受容体チャネルに対する疾患変異の多様な効果

    • Author(s)
      村山 尚、呉林なごみ、小山田英人、鈴木純二、金丸和典、小口勝司、飯野正光、櫻井 隆
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡
    • Related Report
      2013 Research-status Report 2012 Research-status Report
  • [Presentation] C末端悪性高熱変異を有する1型リアノジン受容体チャネルの機能解析

    • Author(s)
      村山 尚、青木良輔、赤塚祐介、呉林なごみ、小山田英人、小口勝司、櫻井 隆
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      船堀
    • Related Report
      2013 Research-status Report 2012 Research-status Report
  • [Remarks] 順天堂大学大学院細胞・分子薬理学ホームページ

    • URL

      http://pharmacology.sakura.ne.jp

    • Related Report
      2014 Annual Research Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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