Novel functions of evolutionarily conserved calpain-7/PalBH in membrane trafficking system.

• Project/Area Number: 20370055
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Tokyo Metropolitan Organization for Medical Research
• Principal Investigator: SORIMACHI Hiroyuki Tokyo Metropolitan Organization for Medical Research, 東京都臨床医学総合研究所, 参事研究員 (10211327)
• Co-Investigator(Kenkyū-buntansha): 小野 弥子 (財)東京都医学研究機構, 東京都臨床医学総合研究所, 主任研究員 (20392376)
• Co-Investigator(Renkei-kenkyūsha): ONO Yasuko 財団法人東京都医学研究機構, 東京都臨床医学総合研究所, 主席研究員 (20392376) ; HATA Shoji 財団法人東京都医学研究機構, 東京都臨床医学総合研究所, 主席研究員 (10392375)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥20,410,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥4,710,000); Fiscal Year 2010: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2009: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2008: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
• Keywords: 細胞内タンパク質分解 / カルパイン / カルシウム / 内膜輸送系 / 胃腸 / 酵素 / 蛋白質 / プロテオリシス / メンブレン・トラフィック / 骨格筋

Research Abstract

Calpains, which are encoded by 15 genes in humans, constitute a family of intracellular Ca^<2+>-dependent proteases. They function to protect living organisms, and, therefore, defects in calpain functions result in lethality or diseases like muscular dystrophy. In this study, we focused on calpain-7/PalBH, which is conserved from human to yeast but has not been studied well so far. As a result, it was suggested that calpain-7 also plays essential roles for mammalian life like calpain-2 and-3.

Research Products

• [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 J.J., Azpitarte M., Doi N., Urtasun M., Kaplan J.C., Lopez de Munain A.
  • Journal Title: Muscle Nerve (in press)
  • Peer Reviewed
• [Journal Article] Calpain cleavage prediction using multiple kernel learning. (2011)
  • Author(s): duVerle D. A., Ono Y., Sorimachi H., Mamitsuka H.
  • Journal Title: PLoS One (in press)
  • Peer Reviewed
• [Journal Article] Calpain chronicle-an enzyme family under multidisciplinary characterization. (2011)
  • Author(s): 反町洋之, 秦勝志, 小野弥子
  • Journal Title: Proc.Jpn.Acad.Ser.B 87(in press)
  • NAID: 130000903736
  • Peer Reviewed
• [Journal Article] Calpain 6, a microtubule-stabilizing protein, regulates Rac1 activity and cell motility through interaction with GEF-H1. (2011)
  • Author(s): Tonami K., Kurihara Y., Arima S., Nishiyama K., Uchijima Y., Asano T., Sorimachi H., Kurihara H.
  • Journal Title: J.Cell Sci. 124(in press) Pages: 2011-2011
• [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: J.Mol.Biol. 407 Pages: 439-449
  • Peer Reviewed
• [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 29(in press)
• [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 62(in press)
• [Journal Article] 胃粘膜防御に果たすカルパインの役割 (2011)
  • Author(s): 秦勝志、反町洋之
  • Journal Title: 日本臨床 69(in press)
• [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 49 Pages: 229-231
  • NAID: 10028117186
• [Journal Article] Non-proteolytic functions of calpain-3 in sarcoplasmic reticulum in skeletal muscles. (2011)
  • Author(s): Ojima, K.
  • Journal Title: J.Mol.Biol. 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): Ojima K., Kawabata Y., Nakao H., Nakao K., Doi N., Kitamura F., Ono Y., Hata S., Suzuki H., Kawahara H., Bogomolovas J., Witt C., Ottenheijm C., Labeit S., Granzier H., Toyama-Sorimachi N., Sorimachi M., Suzuki K., Maeda T., Abe K., Aiba A., Sorimachi H.
  • Journal Title: J.Clin.Invest. 120 Pages: 2672-2683
  • Peer Reviewed
• [Journal Article] Calpain 8/nCL-2 and Calpain 9/nCL-4 constitute an active protease complex, G-calpain, involved in gastric mucosal defense. (2010)
  • Author(s): Hata S., Abe M., Suzuki H., Kitamura F., Toyama-Sorimachi N., Abe K., Sakimura K., Sorimachi H.
  • Journal Title: PLoS Genet.(PLoS Genet. Featured Research選出;SciBX 3(31); doi:10.1038/scibx.2010.956で紹介された) 6
  • 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. 285 Pages: 22986-22998
  • Peer Reviewed
• [Journal Article] Expanding members and roles of the calpain superfamily and their genetically modified animals. (2010)
  • Author(s): 反町洋之, 秦勝志, 小野弥子
  • Journal Title: Exp.Anim. 59 Pages: 549-566
  • NAID: 130000419250
  • Peer Reviewed
• [Journal Article] Une contribution a l'histoire de la decouverte des calpainopathies. (2010)
  • Author(s): Fardeau M., Beckmann J.S., Sorimachi H., Urtizberea J.A.
  • Journal Title: Les Cahiers de Myologie 2 Pages: 5-10
• [Journal Article] Redundant and non-redundant effects of Ca^<2+> and Na^+ on the activation of p94/calpain-3. (2010)
  • Author(s): Ono, Y.
  • Journal Title: Neuromuscul.Disord. Volume: 20 Pages: 608-608
  • Peer Reviewed
• [Journal Article] Skeletal muscle-specific calpain, p94/calpain-3, dynamically distributes in skeletal muscle cells to adapt to physical stress, defects of which cause muscular dystrophy. (2010)
  • Author(s): Ojima, K.
  • Journal Title: Neuromuscul.Disord. Volume: 20 Pages: 598-599
  • Peer Reviewed
• [Journal Article] CaMPDB : a Resource for Calpain and Modulatory Proteolysis. (2010)
  • Author(s): duVerle, D.A.
  • Journal Title: Genome Informatics Volume: 22 Pages: 202-214
  • 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.
  • Journal Title: Neuromuscul. Disord. Volume: 20 Pages: 608-608
  • Peer Reviewed
• [Journal Article] Skeletal muscle-specific calpain, p94/calpain-3, dynamically distributes in skeletal muscle cells to adapt to physical stress, defects of which cause muscular dystrophy. (2010)
  • Author(s): Ojima, K.
  • Journal Title: Neuromuscul. Disord. Volume: 20 Pages: 598-599
  • Peer Reviewed
• [Journal Article] Inhibition of calpain increases LIS1(PAFAH1B1) and partially rescues in vivo phenotypes in a mouse model of lissencephaly. (2009)
  • Author(s): Yamada M., Yoshida Y., Mori D., Takitoh T., Kengaku M., Umeshima H., Takao K., Miyakawa T., Sato M., Sorimachi H., Wynshaw-Boris A., Hirotsune S.
  • Journal Title: Nature Med. 15 Pages: 1202-1207
  • Peer Reviewed
• [Journal Article] CaMPDB : a Resource for Calpain and Modulatory Proteolysis. (2009)
  • Author(s): duVerle D. A., Takigawa I. Ono Y., Sorimachi H., Mamitsuka H.
  • Journal Title: Genome Informatics 22 Pages: 202-214
  • Peer Reviewed
• [Journal Article] A simple single-cell chemical lysis method for analyses of intracellular molecules using an array of picoliter-scale microwells. (2008)
  • Author(s): Sasuga Y., Iwasawa T., Terada K., Oe Y., Sorimachi H., Ohara O., Harada Y.
  • Journal Title: Anal.Chem. 80 Pages: 9141-9149
  • Peer Reviewed
• [Journal Article] Multiple molecular interactions implicate connectin/titin N2A region as a modulating scaffold for p94/calpain 3 activity in skeletal muscle. (2008)
  • Author(s): Hayashi C., Ono Y., Doi N., Kitamura F., Tagami M., Mineki R., Arai T., Taguchi H., Yanagida M., Hirner S., Labeit D., Labeit S., Sorimachi H.
  • Journal Title: J.Biol.Chem. 283 Pages: 14801-14814
  • Peer Reviewed
• [Journal Article] The importance of conserved amino acid residues in protease sub-domain IIb and the IS2 region in p94 for constitutive autolysis. (2008)
  • Author(s): Ono Y., Hayashi C., Doi N., Tagami M., Sorimachi H.
  • Journal Title: FEBS Lett. 582 Pages: 691-698
  • Peer Reviewed
• [Journal Article] Muscle RING-finger protein MuRF1 as a connector of muscle energy metabolism and protein synthesis. (2008)
  • Author(s): Koyama S., Hata S., Witt C. C., Ono Y., Lerche S., Ojima K., Chiba T., Doi N., Kitamura F., Tanaka K., Abe K., Witt S., Rybin V., Gasch A., Franz T., Labeit S., Sorimachi H.
  • Journal Title: J.Mol.Biol. 376 Pages: 1224-1236
  • Peer Reviewed
• [Journal Article] カルパインの生理機能とその不全による病態「カルパイノパチー」 (2008)
  • Author(s): 小野弥子,反町洋之
  • Journal Title: 実験医学 26 Pages: 306-315
• [Journal Article] Multiple molecular interactions implicate connectin/titin N2A region as a modulating scaffold for p94/calpain 3 activity in skeletal muscle (2008)
  • Author(s): Hayashi, C., Ono, Y., Doi, N., Kitamura, F., Tagami, M., Mineki, R., Arai, T., Taguchi, H., Yanagida, M., Hirner, S., Labeit, D., Labeit, S., Sorimachi, H.
  • Journal Title: J. Biol. Chem. 283 Pages: 14801-14814
  • Peer Reviewed
• [Journal Article] A simple single-cell chemical lysis method for analyses of intracellular molecules using an array of picoliter-scale microwells (2008)
  • Author(s): Sasuga, Y., Iwasawa, T., Terada, K., Oe, Y., Sorimachi, H., Ohara, O., Harada, Y.
  • Journal Title: Anal. Chem. 80 Pages: 9141-9149
  • Peer Reviewed
• [Journal Article] The importance of conserved amino acid residues in protease sub-domain IIb and the IS2 region in p94 for constitutive autolysis (2008)
  • Author(s): Ono, Y., Hayashi, C., Doi, N., Tagami, M., Sorimachi, H.
  • Journal Title: FEBS Lett. 582 Pages: 691-698
  • Peer Reviewed
• [Presentation] 胃腸特異的カルパインはストレス性胃粘膜防御に関与する (2011)
  • Author(s): 秦勝志、反町洋之
  • Organizer: 第29回Cytoprotection研究会特別講演
  • Place of Presentation: 京都
  • Year and Date: 2011-03-11
• [Presentation] 胃腸特異的カルパインはストレス性胃粘膜防御に関与する (2011)
  • Author(s): 反町洋之
  • Organizer: 第29回Cytoprotection研究会
  • Place of Presentation: メルパルク京都(京都府)(招待講演)
  • Year and Date: 2011-03-11
• [Presentation] 胃腸特異的カルパインはストレス性胃粘膜防御に関与する (2011)
  • Author(s): 反町洋之
  • Organizer: 第29回Cytoprotection研究会
  • Place of Presentation: メルパルク京都(京都府)
  • Year and Date: 2011-03-11
• [Presentation] 胃腸特異的G-カルパインはカルパイン8と9のヘテロ二量体であり胃粘膜保護に機能する (2010)
  • Author(s): 秦勝志,阿部学,鈴木英紀,北村ふじ子,反町典子,阿部啓子,崎村建司,反町洋之
  • Organizer: BMB2010シンポジウム「生命の鍵を握るタンパク質分解」
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] Skeletal muscle-specific calpain, p94/calpain-3, dynamically distributes in skeletal muscle cells to adapt to physical stress, defects of which cause muscular dystrophy. (2010)
  • Author(s): Ono Y., Ojima K., Torii F., Takaya E., Doi N., Nakagawa K., Hata S., Abe K., Sorimachi H.
  • Organizer: 15th International Congress of the World Muscle Society
  • Place of Presentation: Kumamoto, Japan
  • Year and Date: 2010-10-13
• [Presentation] [Selected for oral presentation] Skeletal muscle-specific calpain, p94/calpain-3, dynamically distributes in skeletal muscle cells to adapt to physical stress, defects of which cause muscular dystrophy. (2010)
  • Author(s): Ojima K., Ono Y., Doi N., Kitamura F., Hata S., Kawabata Y., Suzuki K., Maeda T., Abe K., Nakao H., Aiba A., Nakao K., Suzuki H., Kawahara H., Witt C., Labeit S., Ottenheijm, C., Granzier H., Toyama-Sorimachi N., Sorimachi M., Sorimachi H.
  • Organizer: 15th International Congress of the World Muscle Society
  • Place of Presentation: Kumamoto, Japan
  • Year and Date: 2010-10-13
• [Presentation] Calpains-introduction CHUV (Le Centre Hospitalier Universitaire Vaudois) Special Seminar (2010)
  • Author(s): 小野弥子, 秦勝志, 反町洋之
  • Place of Presentation: Lausanne, Swizerland
  • Year and Date: 2010-10-01
• [Presentation] [The closing lecture] In Memoriam Koichi Suzuki : Calpains in muscles and stomach (2010)
  • Author(s): Ono Y., Hata S., Ojima K., Tonami K., Kitamura F., Ueno M., Takaya E., Granzier H., Labeit S., Sorimachi H.
  • Organizer: 12^<th> Symposium on Proteases, Inhibitors and Biological Control
  • Place of Presentation: Portoroz, Slovenia
  • Year and Date: 2010-09-28
• [Presentation] 鈴木紘一先生追悼講演「CANPからカルパインそしてCAPNへ」 (2010)
  • Author(s): 小野弥子,秦勝志,川原裕之,前田達哉,反町洋之
  • Organizer: 日本病態プロテアーゼ学会第15回大会
  • Place of Presentation: 大阪
  • Year and Date: 2010-08-20
• [Presentation] [The closing lecture] Unique functions of mammalian unconventional calpains. (2010)
  • Author(s): Sorimachi H., Hata S., Ojima K., Labeit S., Ono Y.
  • Organizer: FASEB Summer Research Conferences-The Biology of Calpains in Health & Disease
  • Place of Presentation: Arizona, USA
  • Year and Date: 2010-07-30
• [Presentation] A Koichi Suzuki Legacy : Structure-function relationships of calpain. (2010)
  • Author(s): 反町洋之
  • Organizer: FASEB Summer Research Conferences-The Biology of Calpains in Health & Disease
  • Place of Presentation: Arizona, USA
  • Year and Date: 2010-07-29
• [Presentation] 鈴木先生の哲学とカルパイン (2010)
  • Author(s): 反町洋之
  • Organizer: 鈴木紘一先生メモリアルシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2010-07-06
• [Presentation] Calpain-3 and molecular interactions. (2009)
  • Author(s): Sorimachi H., Ojima K., Hata S., Ono Y.
  • Organizer: Calpaines et Calpainopathies. VII^<es> Journees annuelles de la Societe Francaise de Myologie
  • Place of Presentation: Hendaye, France
  • Year and Date: 2009-10-30
• [Presentation] カルパインの多彩な生理機能とその破綻による病態 (2009)
  • Author(s): 反町洋之,小野弥子,秦勝志,尾嶋孝一
  • Organizer: 第82回日本生化学会大会シンポジウム「プロテオリシスの多彩な生理機能とその破綻による病態」
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-22
• [Presentation] Roles of skeletal muscle-specific calpain, p94/calpain 3, on multiple molecular interactions using connectin/titin N2A region as a modulating scaffold. (2008)
  • Author(s): Sorimachi H., Hayashi C., Hata S., Ojima K., Koyama S., Doi N., Kitamura F., Takaya E., Ueno M., Kaneko N., Ono Y.
  • Organizer: 11^<th> International Symposium on Proteinase Inhibitors and Biological Control
  • Place of Presentation: Portoroz, Slovenia
  • Year and Date: 2008-09-02
• [Presentation] Roles of skeletal muscle-specific calpain, p94/calpain 3, on multiple molecular interactions using connectin/titin N2A region as a modulating scaffold (2008)
  • Author(s): Sorimachi, H., Hayashi, C., Hata, S., Ojima, K., Koyama, S., Doi, N., Kitamura, F., Takaya, E., Ueno, M., Kaneko, N., Ono, Y.
  • Organizer: 11th International Symposium on PROTEINASE INHIBITORS AND BIOLOGICAL CONTROL
  • Place of Presentation: Portoroz, Slovenia
  • Year and Date: 2008-09-02
• [Presentation] Calpain as a "modulator protease" in health and muscle disease. (2008)
  • Author(s): 反町洋之
  • Organizer: Universidad del Pais Vasco/Euskal Herriko Unibertsitatea Summer Course Symposium : Distrofias por Deficit de Calpaina-3: Una Vision General
  • Place of Presentation: San Sebastian, Spain
  • Year and Date: 2008-07-14
• [Remarks] ウェッブサイト等
  • URL: http://www.igakuken.or.jp/calpain
• [Remarks]
  • URL: http://calpain.org/viewer.rb
• [Remarks]
  • URL: http://www.igakuken.or.jp/calpain/
• [Remarks]
  • URL: http://www.igakuken.or.jp/calpain/