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Molecular mechanisms of muscle mass regulation : Identification of a novel protease involved in myostatin activation.

Research Project

Project/Area Number 21500632
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Sports science
Research InstitutionThe University of Tokushima

Principal Investigator

OKUMURA Yuushi  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授 (70294725)

Co-Investigator(Kenkyū-buntansha) NIKAWA Takeshi  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (20263824)
NAKAYA Yutaka  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (50136222)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords筋量決定サイトカイン / 膜結合型プロテアーゼ / 筋萎縮 / 筋委縮
Research Abstract

Muscle mass was decreased by disuse and this condition was thought to regulate by myostatin. Myostatin, a member of TGF-βsuperfamily, has been well characterized as a negative regulator of muscle growth and development. Myostatin is synthesized as a precursor protein and activated by cellular proteases on the cell surface. In this study, as candidate processing proteases for myostatin activation, we could identify a novel protease, MSPL(type II transmembrane serine protease). Interestingly, treatment with MSPL inhibitor to the cells expressing myostatin revealed that a part of it could start differentiation. This result suggested that myostatin activation was regulated by the regulation of MSPL enzymatic activity. To confirm the involvement of MSPL for myostatin activation in vivo, we generated MSPL deficient(MSPL-/-) mice. Unfortunately, from the studies of MSPL-/-mice in unloading condition, no significant differences were observed in the wet weight muscle volume in MSPL-/-mouse compared than in MSPL+/+(Wild-type) mouse(n=1). However, we need to confirm this result by repeating experiments(at least n> 3). The expression and activation of myostatin in MSPL-/-mice are currently being investigated.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (43 results)

All 2011 2010 2009

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (26 results) Book (6 results)

  • [Journal Article] Role of host cellular proteases in the pathogenesis of influenza and influenza-induced multiple organ failure2011

    • Author(s)
      Kido H, Okumura Y, Takahashi E., et al
    • Journal Title

      Biochim Biophys Acta

      Volume: 1824(1) Issue: 1 Pages: 186-194

    • DOI

      10.1016/j.bbapap.2011.07.001

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] RANTES Secreted from Macrophages Disturbed Skeletal Muscle Regeneration after Cardiotoxin Injection in Cbl-b-Deficient Mice2011

    • Author(s)
      Kohno S, Okumura Y, Nikawa T(他10名, 12番目)
    • Journal Title

      Muscle & Nerve

      Volume: 43(2) Issue: 2 Pages: 223-229

    • DOI

      10.1002/mus.21829

    • Related Report
      2011 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] "Hybrid Exercise" prevents muscle atrophy in association with a distinct gene expression pattern2010

    • Author(s)
      Matsugaki T, Nikawa T, Okumura Y(他7名, 6番目)
    • Journal Title

      Kurume Medical Journal

      Volume: 57(4) Pages: 1-8

    • NAID

      130001055545

    • URL

      http://dx.doi.org/10.2739/kurumemedj.57.101

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Novel type II transmembrane serine proteases, MSPL and TMPRSS13, proteolytically activate membrane fusion activity of hemagglutinin of highly pathogenic avian influenza viruses and induce their multicycle replication2010

    • Author(s)
      Okumura Y, Takahashi E, Kido H(他7名, 1番目)
    • Journal Title

      Journal of Virology

      Volume: 84(10) Issue: 10 Pages: 5089-5096

    • DOI

      10.1128/jvi.02605-09

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] "Hybrid Exercise" prevents muscle atrophy in association with a distinct gene expression pattern.2010

    • Author(s)
      Takeshi Nikawa, et al.
    • Journal Title

      Kurume Medical Journal

      Volume: 57(4) Pages: 1-8

    • NAID

      130001055545

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel type II transmembrane serine proteases, MSPL and TMPRSS13, proteolytically activate membrane fusion activity of hemagglutinin of highly pathogenic avian influenza viruses and induce their multicycle replication.2010

    • Author(s)
      Yuushi Okumura, et al.
    • Journal Title

      Journal of Virology

      Volume: 84(10) Pages: 5089-5096

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel type II transmembrane serine proteases, MSPL and TMPRSS13, proteolytically activate membrane fusion activity of hemagglutinin of highly pathogenic avian influenza viruses and induce their multicycle replication.2010

    • Author(s)
      Yuushi Okumura, et al.
    • Journal Title

      Journal of Virology 84(10)(in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ubiquitin ligase Cbl-b is a negative regulator for IGF-1 signaling during muscle atrophy caused by unloading2009

    • Author(s)
      N akao R, Hirasaka K, Goto J, Ishidoh K, Yamada C, Ohno A, Okumura Y, Nonaka I, Yasutomo K, Baldwin KM, Kominami E, Higashibata A, Nagano K, Tanaka K, Yasui N, Mills EM, Takeda S, Nikawa T
    • Journal Title

      Mol Cell Biol

      Volume: 17 Issue: 17 Pages: 4798-4811

    • DOI

      10.1128/mcb.01347-08

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cleavage of the SARS coronavirus spike glycoprotein by airway proteases enhances virus entry into human bronchial epithelial cells in vitro2009

    • Author(s)
      Kam YW, Okumura Y, Kido H(他3名, 2番目)
    • Journal Title

      PLoS One

      Volume: 4(11)

    • URL

      http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007870

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ubiquitin ligase Cbl-b is a negative regulator for insulin-like growth factor 1 signaling during muscle atrophy caused by unloading.2009

    • Author(s)
      Takeshi Nikawa, et al.
    • Journal Title

      Molecular and Cellular Biology. 29(17)

      Pages: 4798-4811

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cleavage of the SARS coronavirus spike glycoprotein by airway proteases enhances virus entry into human bronchial epithelial cells in vitro.2009

    • Author(s)
      Yuushi Okumura, et al.
    • Journal Title

      PLoS One 4(11)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] TYPE II TRANSMEMBRANE SERINE PROTEASES MSPL AND TMPRSS13 PROTEOLYTICALLY ACTIVATE MEMBRANE FUSION ACTIVITY OF HIGHLY PATHOGENIC AVIAN INFLUENZA VIRUS AND INDUCE THEIR MULTICYCLE REPLICATION2011

    • Author(s)
      Yuushi Okumura et al
    • Organizer
      7th General Meeting of the International Proteolysis Society
    • Place of Presentation
      San Diego, CA, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] 高病原性鳥インフルエンザウイルスヘマグルチニンの新規活性化酵素、II型膜結合型セリンプロテアーゼのMSPL/ TMPRSS13の性状解析2011

    • Author(s)
      奥村裕司, 他
    • Organizer
      日本生化学会
    • Place of Presentation
      京都国際会議場(京都府)
    • Related Report
      2011 Final Research Report
  • [Presentation] Unloadingストレス下における筋固有の生体反応機構:オステオアクチビンの発現調節と作用機序について2011

    • Author(s)
      奥村裕司, 他
    • Organizer
      日本栄養・食糧学会
    • Place of Presentation
      御茶の水女子大(東京都)
    • Related Report
      2011 Final Research Report
  • [Presentation] Unloadingストレス下における筋固有の生体反応機構:オステオアクテビンの発現調節と作用機序について2011

    • Author(s)
      奥村裕司, 他
    • Organizer
      日本栄養・食糧学会
    • Place of Presentation
      御茶の水女子大(東京都)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 高病原性鳥インフルエンザウイルスヘマグルテニンの新規活性化酵素、II型膜結合型セリンプロテアーゼのMSPL/TMRSS13の性状解析2011

    • Author(s)
      奥村裕司, 他
    • Organizer
      日本生化学会
    • Place of Presentation
      京都国際会議場(京都府)
    • Related Report
      2011 Annual Research Report
  • [Presentation] TYPE II TRANSMEMBRANE SERINE PROTEASES MSPL AND TMPRSS13 PROTEOLYTICALLY ACTIVATE MEMBRANE FUSION ACTIVITY OF HIGHLY PATHOGENIC AVIAN INFLUENZA VIRUS AND INDUCE2011

    • Author(s)
      Yuushi Okumura, et al
    • Organizer
      7th General Meeting of the International Proteolysis Society
    • Place of Presentation
      San Diego, CA, USA
    • Related Report
      2011 Annual Research Report
  • [Presentation] Sensing mechanism of unloading stress in skeletal muscle : Regulation of ubiquitin ligase, Cbl-b, expression2010

    • Author(s)
      二川健, 他
    • Organizer
      日本分子生物学会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Related Report
      2011 Final Research Report
  • [Presentation] Novel type II transmembrane serine proteases, MSPL and TMPRSS13, proteolytically activate membrane fusion activity of hemagglutinin of highly pathogenic avian influenza viruses and induce their multicycle replication2010

    • Author(s)
      Yuushi Okumura et al
    • Organizer
      Cell Symposia, Influenza ; translating basic insights
    • Place of Presentation
      Washington Marriott Hotel, Washington D. C., USA
    • Related Report
      2011 Final Research Report
  • [Presentation] 高病原性鳥インフルエンザウイルスはII型膜結合型セリンプロテアーゼのMSPL/ TMPRSS13によってヘマグルチニンが切断され、膜融合が活性化される2010

    • Author(s)
      奥村裕司, 他
    • Organizer
      日本ウイルス学会2010
    • Place of Presentation
      あわぎんホール(徳島県)
    • Related Report
      2011 Final Research Report
  • [Presentation] II型膜結合型セリンプロテアーゼ、MSPL/ TMPRSS13による高病原性鳥インフルエンザウイルス感染活性化と、その阻害剤の検討2010

    • Author(s)
      奥村裕司, 他
    • Organizer
      日本病態プロテアーゼ学会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪府)
    • Related Report
      2011 Final Research Report
  • [Presentation] 骨格筋における無重力感知の分子機構:ユビキチンリガーゼCbl-bの発現調節について2010

    • Author(s)
      奥村裕司, 他
    • Organizer
      日本栄養・食糧学会
    • Place of Presentation
      アスティとくしま(徳島県)
    • Related Report
      2011 Final Research Report
  • [Presentation] 骨格筋における無重力感知の分子機構:ユビキチンリガーゼCb1-bの発現調節について2010

    • Author(s)
      奥村裕司, 他
    • Organizer
      日本栄養・食糧学会
    • Place of Presentation
      アスティとくしま(徳島県)
    • Related Report
      2010 Annual Research Report
  • [Presentation] II型膜結合型セリンプロテアーゼ、MSPL/TMPRSS13による高病原性鳥インフルエンザウイルス感染活性化と、その阻害剤の検討2010

    • Author(s)
      奥村裕司, 他
    • Organizer
      日本病態プロテアーゼ学会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪府)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 高病原性鳥インフルエンザウイルスはII型膜結合型セリンプロテアーゼのMSPL/TMPRSS13によってヘマグルチニンが切断され、膜融合が活性化される2010

    • Author(s)
      奥村裕司, 他
    • Organizer
      日本ウイルス学会
    • Place of Presentation
      あわぎんホール(徳島県)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Novel type II transmembrane serine proteases, MSPL and TMPRSS13, proteolytically activate membrane fusion activity of hemagglutinin of highly pathogenic avian influenza viruses and induce their multicycle replication2010

    • Author(s)
      Yuushi Okumura, et al.
    • Organizer
      Cell Symposia, Influenza ; translating basicinsights
    • Place of Presentation
      Washington Marriott Hotel, Washington D.C., USA
    • Related Report
      2010 Annual Research Report
  • [Presentation] Sensing mechanism of unloading stress in skeletal muscle : Regulation of ubiquitin ligase, Cb1-b, expression.2010

    • Author(s)
      二川健, 他
    • Organizer
      日本分子生物学会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Related Report
      2010 Annual Research Report
  • [Presentation]2009

    • Author(s)
      二川健, 他
    • Organizer
      骨格筋のUnloadingストレス感知としての細胞膜上蛋白質分解日本分子生物学会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2011 Final Research Report
  • [Presentation] Role of the host cellular processing proteases in influenza virus infection2009

    • Author(s)
      Yuushi Okumura
    • Organizer
      6th General Meeting of the International Proteolysis Society
    • Place of Presentation
      Surfers Paradise Marriott Resort(Australia)
    • Related Report
      2011 Final Research Report
  • [Presentation] 高病原性鳥インフルエンザウイルスはII型膜結合型セリンプロテアーゼ、MSPL/ TMPRSS13により活性化され、その膜融合活性はインヒビターによって低下する2009

    • Author(s)
      奥村裕司, 他
    • Organizer
      日本生化学会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Related Report
      2011 Final Research Report
  • [Presentation] 高病原性鳥インフルエンザウイルス感染活性化酵素として新たに見出されたII型膜結合型セリンプロテアーゼ、MSPL/ TMPRSS13による膜融合活性の証明2009

    • Author(s)
      奥村裕司, 他
    • Organizer
      日本病態プロテアーゼ学会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪府)
    • Related Report
      2011 Final Research Report
  • [Presentation] 寝たきりにおける筋固有の応答機構:オステオアクチビンの発現調節と活性化、作用機構について2009

    • Author(s)
      奥村裕司, 他
    • Organizer
      日本栄養・食糧学会
    • Place of Presentation
      日本ブリックホール(長崎県)
    • Related Report
      2011 Final Research Report
  • [Presentation] 寝たきりにおける筋固有の応答機構:オステオアクチビンの発現調節と活性化、作用機構について2009

    • Author(s)
      奥村裕司, 他
    • Organizer
      日本栄養・食糧学会
    • Place of Presentation
      ブリックホール(長崎県)
    • Related Report
      2009 Annual Research Report
  • [Presentation] 高病原性鳥インフルエンザウイルス感染活性化酵素として新たに見出されたII型膜結合型セリンプロテアーゼ、MSPL/TMPRSS13による膜融合活性の証明2009

    • Author(s)
      奥村裕司, 他
    • Organizer
      日本病態プロテアーゼ学会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪府)
    • Related Report
      2009 Annual Research Report
  • [Presentation] 高病原性鳥インフルエンザウイルスはII型膜結合型セリンプロテアーゼ、MSPL/TMPRSS13により活性化され、その膜融合活性はインヒビターによって低下する2009

    • Author(s)
      奥村裕司, 他
    • Organizer
      日本生化学会
    • Place of Presentation
      神戸国際会議場(兵庫県〉
    • Related Report
      2009 Annual Research Report
  • [Presentation] Role of the host cellular processing proteases in influenza virus infection2009

    • Author(s)
      Yuushi Okumura
    • Organizer
      6^<th> General Meeting of the International Proteolysis Society
    • Place of Presentation
      Surfers Paradise Marriott Resort (Australia)
    • Related Report
      2009 Annual Research Report
  • [Presentation] 骨格筋のUnloadingストレス感知としての細胞膜上蛋白質分解2009

    • Author(s)
      二川健, 他
    • Organizer
      日本分子生物学会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2009 Annual Research Report
  • [Book] Mechanobiology in Space : Mechanosensing Biology(Ed M. Noda)2011

    • Author(s)
      Yuushi Okumura, and Takeshi Nikawa
    • Total Pages
      8
    • Publisher
      Springer社
    • Related Report
      2011 Final Research Report
  • [Book] Surgery Frontier-蛋白質の構造、性質、分類-2011

    • Author(s)
      奥村裕司、二川健
    • Total Pages
      3
    • Publisher
      メディカルレビュー社
    • Related Report
      2011 Final Research Report
  • [Book] Surgery Frontier-蛋白質の合成と分解-2011

    • Author(s)
      奥村裕司、二川健
    • Total Pages
      3
    • Publisher
      メディカルレビュー社
    • Related Report
      2011 Final Research Report
  • [Book] Surgery Frontier-蛋白質の構造、性質、分類-2011

    • Author(s)
      奥村裕司, 他
    • Total Pages
      3
    • Publisher
      メディカルレビュー社
    • Related Report
      2011 Annual Research Report
  • [Book] Surgery Frontier-蛋白質の合成と分解-2011

    • Author(s)
      奥村裕司, 他
    • Total Pages
      3
    • Publisher
      メディカルレビュー社
    • Related Report
      2011 Annual Research Report
  • [Book] Mechanobiology in Space : In Mechanosensing Biology(Ed M.Noda)2011

    • Author(s)
      Yuushi Okumura, Takeshi NikaWa
    • Total Pages
      8
    • Publisher
      Springer
    • Related Report
      2010 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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