Functional aspect of skeletal muscle-specific calpain system

• Project/Area Number: 22770139
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: 公益財団法人東京都医学総合研究所 (2011); Tokyo Metropolitan Organization for Medical Research (2010)
• Principal Investigator: ONO Yasuko 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 主席研究員 (20392376)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: カルパイン / 骨格筋 / プロテアーゼ / 自己消化活性 / サルコメア / 筋ジストロフィー / ノックインマウス / プロテオーム

Research Abstract

Regulatory mechanism of calpain3 (p94), a responsible gene product for LGMD2A, in skeletal muscle was investigated. It was demonstrated that Na^+ as well as Ca^<2+> activates calpain3. In addition, a novel protein, PLEIAD/SIMC1/C5orf25, was found to be a potential scaffold for calpain3.

Research Products

• [Journal Article] PLEIAD/SIMC1/C5orf25, a Novel Autolysis Regulator for a Skeletal-Muscle-Specific Calpain, CAPN3, Scaffolds a CAPN3 Substrate, CTBP1 (2013)
  • Author(s): Ono, Y., Iemura, SI., Novak, S. M., Doi, N., Kitamura, F., Natsume, T., Gregorio, C. C., Sorimachi H
  • Journal Title: J. Mol. Biol Volume: (in press) Issue: 16 Pages: 2955-2972
  • DOI: 10.1016/j.jmb.2013.05.009
  • Peer Reviewed
• [Journal Article] Understanding the substrate specificity of conventional calpains (2012)
  • Author(s): Sorimachi, H., Mamitsuka, H., Ono, Y
  • Journal Title: Biol. Chem Volume: 393 Issue: 9 Pages: 853-871
  • DOI: 10.1515/hsz-2012-0143
  • Peer Reviewed
• [Journal Article] Regulation and physiological roles of the calpain system in muscular disorders (2012)
  • Author(s): Sorimachi, H., Ono, Y
  • Journal Title: Cardiovasc. Res Volume: 96 Issue: 1 Pages: 11-22
  • DOI: 10.1093/cvr/cvs157
  • Peer Reviewed
• [Journal Article] Calpains - An elaborate proteolytic system (2012)
  • Author(s): Ono Y, Sorimachi H
  • Journal Title: Biochim Biophys Acta Volume: 1824 Issue: 1 Pages: 224-236
  • DOI: 10.1016/j.bbapap.2011.08.005
  • Peer Reviewed
• [Journal Article] Does the severity of the LGMD2A phenotype in compound heterozygotes depend on the combination of mutations? (2011)
  • Author(s): Saenz A, Ono Y, Sorimachi H, Goicoechea M, Leturcq F, Blazquez L, Garcia-Bragado F, Marina A, Poza JJ, Azpitarte M, Doi N, Urtasun M, Kaplan JC, Lopez de Munain A
  • Journal Title: Muscle and Nerve Volume: 44 Issue: 5 Pages: 710-714
  • DOI: 10.1002/mus.22194
  • Peer Reviewed
• [Journal Article] Calpain chronicle-an enzyme family under multidisciplinary characterization (2011)
  • Author(s): Sorimachi, H., Hata, S., Ono, Y
  • Journal Title: Proc Jpn Acad Ser B Phys Biol Sci Volume: 87 Pages: 287-327
  • NAID: 130000903736
  • URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153876/
  • Peer Reviewed
• [Journal Article] Impact of genetic insights into calpain biology (2011)
  • Author(s): Sorimachi H, Hata S, Ono Y
  • Journal Title: J Biochem Volume: 150 Issue: 1 Pages: 23-37
  • DOI: 10.1093/jb/mvr070
  • NAID: 10030586192
  • Peer Reviewed
• [Journal Article] Calpain cleavage prediction using multiple kernel learning. (2011)
  • Author(s): duVerle DA, Ono Y, Sorimachi H, Mamitsuka H
  • Journal Title: PLoS One Volume: 6 Issue: 5 Pages: e19035-e19035
  • DOI: 10.1371/journal.pone.0019035
  • 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, HataS, Suzuki H, Granzier H, Sorimachi H
  • Journal Title: J Mol Biol Volume: 407 Issue: 3 Pages: 439-449
  • DOI: 10.1016/j.jmb.2011.01.057
  • Peer Reviewed
• [Journal Article] 肢帯型筋ジストロフィーの発症機構 (2011)
  • Author(s): 反町洋之,小野弥子
  • Journal Title: 生体の科学 Volume: 62-2 Pages: 95-99
• [Journal Article] 骨格筋特異的カルパイン-3の活性制御因子は細胞内Na^+～例外か多様性か (2011)
  • Author(s): 小野弥子,反町洋之
  • Journal Title: 化学と生物 Volume: 49-4 Pages: 229-231
  • NAID: 10028117186
• [Journal Article] カルパインの組織機能論 (2011)
  • Author(s): 反町洋之,秦勝志,小野弥子
  • Journal Title: 実験医学 Volume: 29 Pages: 1882-1890
• [Journal Article] Calpain chronicle-an enzyme family under multidisciplinary characterization. (2011)
  • Author(s): 反町洋之
  • Journal Title: Proc Jpn Acad Ser B Phys Biol Sci Volume: 87 Pages: 287-327
  • Peer Reviewed
• [Journal Article] Expanding members and roles of the calpain superfamily and their genetically modified animals (2010)
  • Author(s): Sorimachi, H., Hata, S., and Ono, Y
  • Journal Title: Exp. Anim Volume: 59 Pages: 549-566
  • NAID: 130000419250
  • URL: https://www.jstage.jst.go.jp/article/expanim/59/5/59_5_549/_article
  • 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): Ojima K, Kawabata Y, Nakao H, Nakao K, Doi N, Kitamura F, Ono Y, HataS, Suzuki H, Kawahara H, Bogomolovas J,Will C, Ottenheijm C, LabeitS, Granzier H, Toyama-Sorimachi N, Sorimachi M, Suzuki K, Maeda T, Abe K, Aiba A, Sorimachi H
  • Journal Title: J Clin Invest Volume: 120 Issue: 8 Pages: 2672-2683
  • DOI: 10.1172/jci40658
  • 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: J Biol Chem Volume: 285 Issue: 30 Pages: 22986-22998
  • DOI: 10.1074/jbc.m110.126946
  • 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: J.Biol.Chem. Volume: 285 Pages: 22986-22998
  • Peer Reviewed
• [Journal Article] Redundant and non-redundant effects of Ca^<2+> and Na^+ on the activation of p94/calpain-3 (2010)
  • Author(s): Ono, Y., Ojima, K., Torii, F., Takaya, E., Doi, N., Nakagawa, K., Hata, S., Abe, K., Sorimachi, H.
  • Journal Title: Neuromuscul.Disord. Volume: 20 Pages: 608-608
• [Presentation] 筋特異的カルパインCAPN3/p94活性化機構における分子間相補の解析 (Inter-molecular interaction involved in the activation of CAPN3/p94) (2012)
  • Author(s): 小野弥子,田尾あすみ,北村ふじ子,反町洋之
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] STRUCTURE-FUNCTION RELATIONSHIP OF Na^+-DEPENDENT ACTIVITY OF MUSCLE-SPECIFIC CALPAIN (2012)
  • Author(s): Ono,Y., Takaya, E., Doi, N., Kitamura, F., Sorimachi, H
  • Organizer: SPIBC 2012(第13回プロテアーゼおよびその阻害剤と生体制御に関する国際会議)
  • Place of Presentation: Portoroz, Slovenia
• [Presentation] Characterization of sodium-dependent protease activity of muscle-specific calpain (2012)
  • Author(s): Ono,Y., Ouchi, F., Kitamura, F., Sorimachi, H
  • Organizer: CAPN3. EMC2012(第41回ヨーロッパ筋機能研究学会)
  • Place of Presentation: Rhodes, Greek
• [Presentation] 筋特異的カルパインCAPN3/p94の新奇活性化機構の解析 (2011)
  • Author(s): 小野弥子,田尾あすみ,北村ふじ子,反町洋之
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-14
• [Presentation] Functional aspects of unique autolytic activity of CAPN3 (2011)
  • Author(s): Ono, Y
  • Organizer: Department of Cellular and Molecular Medicine
  • Place of Presentation: University of Arizona, Tucson, USA
  • Year and Date: 2011-02-11
• [Presentation] Structure-function relationship of Na^+-dependent activity of calpain-3/p94 (2011)
  • Author(s): Ono, Y
  • Organizer: Korea-Japan symposium on protein metabolism
  • Place of Presentation: Seoul National University, Seoul, Korea
  • Year and Date: 2011-01-28
• [Presentation] Structure-function relationship of Na^+-dependent activity of calpain-3/p94 (2011)
  • Author(s): Ono, Y.
  • Organizer: Korea-Japan symposium on protein metabolism
  • Place of Presentation: ソウル大学(韓国)(招待講演)
  • Year and Date: 2011-01-28
• [Presentation] Does the severity of the LGMD2A phenotype in compound heterozygotes depend on the combination of mutations? (2011)
  • Author(s): Ono, Y., Saenz, A., Sorimachi, H., Lopez de Munain, A
  • Organizer: The 7th International Proteolysis Society meeting
  • Place of Presentation: San Diego, USA
• [Presentation] Autolytic activity of skeletal muscle-specific calpain, CAPN3, diversifies its functions? (2011)
  • Author(s): Ono, Y., Doi, N., Kitamura, F., Sorimachi, H
  • Organizer: CMM, MCB, and CBC joint retreat, Biosphere 2
  • Place of Presentation: University of Arizona, Tucson, USA
• [Presentation] Structure-Function relationship of Na^+-dependent activity of calpain-3/p94 (2011)
  • Author(s): Ono, Y., Takaya, E., Doi, N., Kitamura, F., Sorimachi, H
  • Organizer: The 17th Symposium on Ca^<2+>-Binding Proteins and Ca^<2+> Function in Health and Disease
  • Place of Presentation: Beijing, China
• [Presentation] Calpain-3/p94のNa依存性について (2011)
  • Author(s): 小野弥子
  • Organizer: 平成22年度科学研究費補助金特定領域研究「タンパク質分解による細胞・個体機能の制御」班会議
  • Place of Presentation: 札幌
• [Presentation] Structure-Function relationship of Na+-dependent activity of calpain-3/p94. (2011)
  • Author(s): 小野弥子
  • Organizer: The 17th Symposium on Ca2+-Binding Proteins and Ca2+ Function in Health and Disease
  • Place of Presentation: Beijing, China
• [Presentation] Calpain3/p94自己消化機構の解析 (2010)
  • Author(s): 小野弥子, 土井奈穂子, 高谷恵美, 北村ふじ子, 反町洋之
  • Organizer: BMB2010(第33回日本分子生物学会年会・第83回日本生化学会大会合同大会)
  • Place of Presentation: ポートピアホテル(神戸)
  • Year and Date: 2010-12-10
• [Presentation] Functions of calpain-3/p94 indicated by its unique properties (2010)
  • Author(s): Ono, Y
  • Organizer: CHUV (Le Centre Hospitalier Universitaire Vaudois) Special Seminar
  • Place of Presentation: Lausanne, Switzerland
  • Year and Date: 2010-10-01
• [Presentation] Functions of calpain-3/p94 indicated by its unique properties (2010)
  • Author(s): Ono, Y.
  • Organizer: CHUV (Le Centre Hospitalier Universitaire Vaudois) Special Seminar
  • Place of Presentation: CHUV大学(スイス)(招待講演)
  • Year and Date: 2010-10-01
• [Presentation] Skeletal muscle-specific calpain, p94/calpain-3, 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.
  • Organizer: XIIth Symposium on Proteases, Inhibitors and Biological Control
  • Place of Presentation: Portoroz(スロベニア)
  • Year and Date: 2010-09-28
• [Presentation] Characteristics of p94/calpain-3 as an intracellular Na^+-dependent protease (2010)
  • Author(s): Ono, Y., Ojima, K., Torii, F., Takaya, E., Doi, N., Nakagawa, K., Hata, S., Abe, K., and Sorimachi, H
  • Organizer: FASEB Summer Research Conferences . Biology of the calpains in Health and Disease, Carefree, AZ
  • Place of Presentation: USA
  • Year and Date: 2010-07-28
• [Presentation] Characteristics of p94/calpain 3 as 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.
  • Organizer: FASEB Summer Research Conferences
  • Place of Presentation: Carefree, AZ(米国)
  • Year and Date: 2010-07-28
• [Presentation] p94/calpain3自己消化機構の解析 (2010)
  • Author(s): 小野弥子、土井奈穂子、高谷恵美、北村ふじ子、反町洋之
  • Organizer: 第10回日本蛋白質科学会年会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2010-06-18
• [Presentation] Calpain3/p94自己消化機構の解析 (2010)
  • Author(s): 小野弥子,土井奈穂子,高谷恵美,北村ふじ子,反町洋之
  • Organizer: BMB2010 (第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会)
  • Place of Presentation: 神戸
• [Presentation] Redundant and non-redundant effects of Ca^<2+> and Na^+ on the activation of p94/calpain 3 (2010)
  • Author(s): Ono, Y., Ojima, K., Torii, F., Takaya, E., Doi, N., Nakagawa, K., Hata, S., Abe, K., Sorimachi, H
  • Organizer: The 15th International Congress of the World Muscle Society
  • Place of Presentation: Kumamoto, Japan
• [Presentation] Skeletal muscle-specific calpain, p94/calpain-3, 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
  • Organizer: XIIth Symposium on Proteases, Inhibitors and Biological Control
  • Place of Presentation: Portoroz, Slovenia
• [Presentation] p94/calpain3自己消化機構の解析, Inter/Intra molecular interaction involved in the autocatalytic proteolysis of p94/calpain 3 (2010)
  • Author(s): 小野弥子,土井奈穂子,高谷恵美,北村ふじ子,反町洋之
  • Organizer: 第10回日本蛋白質科学会年会
  • Place of Presentation: 札幌
• [Presentation] 筋特異的カルパインCAPN3/p94の新奇活性化機構の解析
  • Author(s): 小野弥子
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Book] Chapter 471: μ-calpain, Chapter 472: m-calpain, Chapter 473: Muscle calpain, Chapter 474: Gastrointestinal calpain, Chapter 476: Other calpains. in: Handbook of Proteolytic enzymes, 3rd Edition. N.D. RawlIngs, G. Salvesen, editors (2013)
  • Author(s): Sorimachi, H., Hata, S., Ono, Y
  • Total Pages: 3932
  • Publisher: Elsevier Academic Press (Oxford)
• [Book] In "Encyclopedia of Biological Chemistry 2^<nd> Edition (2013)
  • Author(s): Sorimachi, H., Hata, S., and Ono, Y. Calpain
  • Total Pages: 3232
  • Publisher: Elsevier, Oxford; eds., M.D. Lane and W. J. Lennarz
• [Book] 「カルパイン」,モデル動物利用マニュアル…<生物機能モデルと新しいリソース・リサーチツール> (2011)
  • Author(s): 反町洋之,秦勝志,小野弥子
  • Total Pages: 671
  • Publisher: 株式会社LIC
• [Book] 肢帯型筋ジストロフィーの発症機構 （生体の科学 62-2） (2011)
  • Author(s): 反町洋之
  • Total Pages: 5
  • Publisher: 医学書院
• [Book] 骨格筋特異的カルパイン-3の活性制御因子は細胞内Na+～例外か多様性か（化学と生物 49-4）） (2011)
  • Author(s): 小野弥子
  • Total Pages: 3
  • Publisher: 学会出版センター
• [Book] カルパインの組織機能論（実験医学 29） (2011)
  • Author(s): 反町洋之
  • Total Pages: 9
  • Publisher: 羊土社
• [Book] カルパイン（生物機能モデルと新しいリソース・リサーチマニュアル） (2011)
  • Author(s): 反町洋之
  • Total Pages: 17
  • Publisher: 株式会社LIC
• [Remarks]
  • URL: http://www.igakuken.or.jp/calpain/
• [Remarks] 所属機関ホームページ
  • URL: http://www.igakuken.or.jp/calpain/
• [Remarks]
  • URL: http://www.rinshoken.or.jp/ER/