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Therapeutic strategy for muscular dystrophy via regulation of STIM1 mediated Ca2+ homeostasis

Research Project

Project/Area Number 15K09328
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionTeikyo University

Principal Investigator

Shimizu Teruo  帝京大学, 医療技術学部, 特任教授 (00107666)

Co-Investigator(Kenkyū-buntansha) 真先 敏弘  帝京科学大学, 医療科学部, 教授 (00585028)
萩原 宏毅  帝京科学大学, 医療科学部, 教授 (80276732)
Co-Investigator(Renkei-kenkyūsha) Matsumura Kiichiro  帝京大学, 医学部, 教授 (50260922)
Saito Fumiaki  帝京大学, 医学部, 准教授 (40286993)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords筋ジストロフィー / 細管集合体ミオパチー / カルシウムホメオスタシス / STIM1 / ORAI1
Outline of Final Research Achievements

Recently, STIM1-ORAI1 signaling is receiving attention as molecules regulating calcium homeostasis in skeletal muscle. In this study, we investigated the pathomechanism of a novel mutation of STIM1 we identified in a family with tubular aggregate myopathy. In contrast to the previous reports, this novel mutation resides in the cytoplasmic domain of STIM1. Gene transfer experiments using cultured myoblasts exhibit that the mutant STIM1 induces marked reduction of intracellular calcium concentration and inhibits puncta formation of STIM1 with tapsigargin, which is necessary for ORAI1 activation. Taken together, in the family with the novel mutation, tubular aggregate myopathy is caused by a distinct pathomechanism from that previously proposed, i.e. excessive influx of calcium.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (8 results)

All 2017 2016 2015

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Tubular aggregate myopathy caused by a novel mutation in the cytoplasmic domain of STIM12016

    • Author(s)
      Oakum H, Saito F, Jun Mitsui J, Hara Y, Hatanaka Y, Ikeda M, Shimizu T, Matsumura K, Shimizu J, Tsui S, Sonoo M.
    • Journal Title

      Neurol Genet

      Volume: 2 Issue: 1 Pages: 50-50

    • DOI

      10.1212/nxg.0000000000000050

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Excision of myotonic dystrophy CTG repeat using CRISPR/Cas9 genome editting2017

    • Author(s)
      斉藤史明、池田美樹、萩原宏毅、真先敏弘、清水輝夫、松村喜一郎、園生雅弘
    • Organizer
      第3回日本筋学会学術終会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 筋強直性ジストロフィーに対するゲノム編集治療の基礎的研究2017

    • Author(s)
      斉藤史明、池田美樹、萩原宏毅、真先敏弘、清水輝夫、松村喜一郎、園生雅弘
    • Organizer
      第2回日本ゲノム編集学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Tubular aggregate myopathy caused by a novel mutation in the cytoplasmic domain of STIM1.2016

    • Author(s)
      Saito F, Okuma H, Mitsui J, Hara Y, Hatanaka Y, Ikada M, Shimizu T, Matsumura K, Shimizu J, Tsuji S, Sonoo M
    • Organizer
      21st International congress of the World Muscle Society
    • Place of Presentation
      スペイン・グラナダ
    • Year and Date
      2016-10-04
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Novel mutation of STIM1 causes dysregulation of Ca2+ homeostasis in tubular aggregate myopathy.2016

    • Author(s)
      斉藤史明、原雄二、三井純、畑中裕己、萩原宏毅、真先敏弘、清水輝夫、清水潤、辻省次、松村喜一郎、園生雅弘
    • Organizer
      第57回日本神経学会学術大会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県神戸市)
    • Year and Date
      2016-05-18
    • Related Report
      2016 Research-status Report
  • [Presentation] α-dystroglycan N末端ドメインの過剰発現がマウス骨格筋に及ぼす影響に関する検討2015

    • Author(s)
      斉藤史明、大熊秀彦、池田美樹、萩原宏毅、真先敏弘、清水輝夫、松村喜一郎、園生雅弘.
    • 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
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Tubular aggregate myopathyにおける新規STIM1変異と筋芽細胞に及ぼす影響2015

    • Author(s)
      大熊秀彦、三井純、大森亜希、肥田あゆみ、畑中裕己、松村喜一郎、清水潤、 辻省次、園生雅弘、斉藤史明.
    • Organizer
      第56回日本神経学会学術大会
    • Place of Presentation
      新潟コンベンションセンター(新潟県新潟市)
    • Year and Date
      2015-05-20
    • Related Report
      2015 Research-status Report
  • [Presentation] Analysis of the functional role of α-dystroglycan N-terminal domain in vivo2015

    • Author(s)
      斉藤史明、大熊秀彦、萩原宏毅、真先敏弘、池田美樹、清水輝夫、園生雅 弘、松村喜一郎.
    • Organizer
      第56回日本神経学会学術大会
    • Place of Presentation
      新潟コンベンションセンター(新潟県新潟市)
    • Year and Date
      2015-05-20
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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