Skeletal muscle specific calpain p94 mediated signal transduction system

• Project/Area Number: 20500369
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurophysiology and muscle physiology
• Research Institution: National Agricultural Research Organization
• Principal Investigator: OJIMA Koichi National Agricultural Research Organization, 畜産草地研究所, 研究員 (60415544)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: カルパイン / 骨格筋 / 筋ジストロフィー / タンパク質分解酵素 / 蛋白質分解酵素 / p94

Research Abstract

p94 is predominantly expressed in skeletal muscle and is a member of calpains that are Ca^<2+>-requiring intracellular cysteine proteases. In this study, we revealed that loss of p94 proease activity impaired adaptation to physical stress, accompanied by deficiency in exercise-dependent up-regulation of muscle ankyrin-repeat protein-2 and heat-shock proteins. Furthermore, p94 changes its localization in myocytes depending on sarcomere conditions to mediate signal transduction in response to external stress, and its protease activity maintains myocyte homeostasis, disruption of which leads to muscular dystrophy.

Research Products

• [Journal Article] Non-proteolytic functions of calpain-3 in sarcoplasmic reticulum in skeletal muscles. (2011)
  • Author(s): K.Ojima, Y.Ono, C.Ottenheijm, S.Hata, H.Suzuki, H.Granzier, H.Sorimachi.
  • Journal Title: J.Mol.Biol. 407 Pages: 439-449
  • Peer Reviewed
• [Journal Article] Non-proteolytic functions of calpain-3 in sarcoplasmic reticulum in skeletal muscles (2011)
  • Author(s): Ojima, K., Ono, Y., Ottenheijm, C., Hata, S., Suzuki, H., Granzier, H., Sorimachi, H.
  • Journal Title: Journal of Molecular Biology Volume: 407 Pages: 439-449
  • Peer Reviewed
• [Journal Article] Dynamic distribution of muscle-specific calpain in mice has a key role in physical-stress adaptation and is impaired in muscular dystrophy. (2010)
  • Author(s): K.Ojima, Y.Kawabata, H.Nakao, K.Nakao, N.Doi, F.Kitamura, Y.Ono, S.Hata, H.Suzuki, H.Kawahara, J.Bogomolovas, C.Witt, C.Ottenheijm, S.Labeit, H.Granzier, N.Toyama-Sorimachi, M.Sorimachi, K.Suzuki, T.Maeda, K.Abe, A.Aiba, H.Sorimachi.
  • Journal Title: J.Clin.Invest. 120 Pages: 2672-2683
  • Peer Reviewed
• [Journal Article] Skeletal muscle-specific calpain is an intracellular Na+-dependent protease. (2010)
  • Author(s): Y.Ono, K.Ojima, F.Torii, E.Takaya, N.Doi, K.Nakagawa, S.Hata, K.Abe, H. Sorimachi.
  • Journal Title: J.Biol.Chem. 285 Pages: 22986-22998
  • Peer Reviewed
• [Journal Article] Dynamic distribution of muscle-specific calpain in mice has a key role in physical-stress adaptation and is impaired in muscular dysirophy (2010)
  • Author(s): Ojima, K., Kawabata, Y., Nakao, H., Nakao, K., Doi, N., Kitamura, F., Ono, Y., Hata, S., Suzuki, H., Kawahara, H., Bogomolovas, J., Witt, C., Ottenbeijm, C., Labeit, S., Granzier, H., Toyama-Smorimachi, N., Sorimachi, M., Suzuki, K., Macda, T., Abe, K., Aiba, A., Sorimachi, H.
  • Journal Title: Journal of Clinical Investigation Volume: 120 Pages: 2672-2683
  • Peer Reviewed
• [Journal Article] Skeletal muscle-specific calpain is an intracellular Na+-dependent protease (2010)
  • Author(s): Ono, Y., Ojima, K., Torii, F., Takaya, E., Doi, N., Nakagawa, K., Hata, S., Abe, K., Sorimachi, H.
  • Journal Title: Journal of Biological Chemistry Volume: 285 Pages: 22986-22998
  • Peer Reviewed
• [Presentation] Dynamic distribution of muscle-specific calpain 3/p94 plays a key role in physical-stress adaptation and its defects by loss of activity cause muscular dystrophy. (2010)
  • Author(s): K.Ojima, Y.Kawabata, H.Nakao, K.Nakao, N Doi, F.Kitamura, Y.Ono, S.Hata, H.Kawahara, S.Labeit, N.Toyama-Sorimachi, M.Sorimachi, K.Suzuki, T.Maeda, A.Aiba, H.Sorimachi.
  • Organizer: The Biology of Calpians in Health and Disease. FASEB Summer Research Conference.
  • Place of Presentation: Carefree, AZ, USA
• [Presentation] Loss of calpain-3 protease activity impairs its distribution and muscle physical-stress adaption, resulting in muscular dystrophy. (2010)
  • Author(s): K.Ojima, Y.Kawabata, H.Nakao, K.Nakao, N.Doi, F.Kitamura, Y.Ono, S.Hata, H.Kawahara, S.Labeit, N.Toyama-Sorimachi, M.Sorimachi, T.Maeda, A.Aiba, H.Sorimachi.
  • Organizer: The 50th Annual Meeting of the American Society for Cell Biology.
  • Place of Presentation: Philadelphia, PA, USA
• [Presentation] Loss of calpain-3 protease activity impairs its distribution and muscle physical-stress adaption, resulting in muscular dystrophy. (2010)
  • Author(s): Ojima, K., Kawabata, Y., Nakao, H., Nakao, K., Doi, N., Kitamura, F., Ono, Y., Hata, S., Kawahara, H., Labeit, S., Toyama-Sorimachi, N., Sorimachi, M., Maeda, T., Aiba, A., Sorimachi., H.
  • Organizer: The 50th Annual Meeting of the American Society for Cell Biology
  • Place of Presentation: Philadelphia, PA.USA
• [Presentation] Dynamic distribution of muscle-specific calpain 3/p94 plays a key role in physical-stress adaptation and its defects by loss of activity cause muscular dystrophy. (2010)
  • Author(s): Ojima, K., Kawabata, Y., Nakao, H., Nakao, K., Doi, N., Kitamura, F., Ono, Y., Hata, S., Kawahara, H., Labeit, S., Toyama-Sorimachi, N., Sorimachi, M., Suzuki, K., Maeda, T., Aiba, A., Sorimachi, H.
  • Organizer: The Biology of Calpians in Health and Disease. FASEB Summer Research Conference
  • Place of Presentation: Carefree, AZ, USA
• [Presentation] Quantitative mass spectrometry-based protein profiling of skeletal muscle cell differentiation in vitro. (2009)
  • Author(s): Koichi Ojima
  • Organizer: The 49th Annual Meeting of the American Society for Cell Biology
  • Place of Presentation: San Diego, CA.USA
  • Year and Date: 2009-12-07
• [Presentation] 骨格筋特異的カルパインの筋小胞体における機能 (2009)
  • Author(s): 尾嶋孝一
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2009-10-23
• [Presentation] 骨格筋特異的カルパインの筋小胞体における機能 (2009)
  • Author(s): 尾嶋孝一,小野弥子,土井菜穂子,北村ふじ子,秦勝志, S.Labeit, H.Granzier,千国幸一, 反町洋之
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸(兵庫)
• [Presentation] Quantitative mass spectrometry-based protein profiling of skeletal muscle cell differentiation in vitro. (2009)
  • Author(s): K.Ojima, I.Nakajima, M.Oe, M.Shibata, H.Sorimachi, K.Chikuni.
  • Organizer: The 49th Annual Meeting of the American Society for Cell Biology
  • Place of Presentation: San Diego, CA
• [Presentation] Quantitative proteomic analysis of skeletal muscles subjected to exercise (2008)
  • Author(s): Koichi Ojima
  • Organizer: The 48th Annual Meeting of the American Society for Cell Biology
  • Place of Presentation: San Francisco, CA. USA
  • Year and Date: 2008-12-15
• [Presentation] 骨格筋特異的カルパインは運動負荷による筋損傷をプロテアーゼ活性により防御する (2008)
  • Author(s): 尾嶋孝一
  • Organizer: 第8回日本蛋白質科学会
  • Place of Presentation: 東京都江戸川区
  • Year and Date: 2008-06-11
• [Presentation] 骨格筋特異的カルパインは運動負荷による筋損傷をプロテアーゼ活性により防御する (2008)
  • Author(s): 尾嶋孝一,川畑順子,中尾晴美,小野弥子,土井菜穂子,北村ふじ子,秦勝志,川原裕之,C.Witt, S.Labeit,鈴木紘一,阿部啓子,前田達哉,餐場篤, 反町洋之
  • Organizer: 第8回日本蛋白質科学会
  • Place of Presentation: 江戸川区
• [Presentation] Quantitative proteomic analysis of skeletal muscles subjected to exercise. (2008)
  • Author(s): K.Ojima, H.Sorimachi.
  • Organizer: The 48th Annual Meeting of the American Society for Cell Biology
  • Place of Presentation: San Francisco, CA
• [Remarks] 朝日新聞(科学欄)2010年7月16日
• [Remarks] 都政新報(第一面)2010年7月9日