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2005 Fiscal Year Final Research Report Summary

Functional analysis of stomach-specific calpain.

Research Project

Project/Area Number 15380089
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Food science
Research InstitutionTokyo Metropolitan Organization for Medical Research (2004-2005)
The University of Tokyo (2003)

Principal Investigator

SORIMACHI Hiroyuki  Tokyo Metropolitan Organization for Medical Research, The Tokyo Metropolitan Institute of Medical Science, 東京都臨床医学総合研究所, 副参事研究員 (10211327)

Project Period (FY) 2003 – 2005
Keywordscalpain / enzyme / protein / proteolysis / mutant mouse / stomach / membrane trafficking / COPI
Research Abstract

Calpains are a cytosolic Ca2+-regulated cysteine protease. Calpains directly interact with intracellular proteins to modify or transform functions and/or activities of their substrates, and are thus called "modulator protease". Mammals have 14 independent genes for calpains, about half of which are expressed tissue-specifically. These tissue-specific calpain are expected to be involved in specific functions developed in the specific tissues, and, therefore, their physiological functions are of great interest. One of the tissue-specific calpain, nCL-2/-2', is predominantly expressed in the stomach, especially, in the epithelial "pit" cells. The pit cells secrete mucus to protect the stomach from acid and bacteria. Therefore, nCL-2 functions are considered to be related with mucus secretion mechanisms.
To elucidate physiological functions of nCL-2, we constructed nCL-2:C105S "knock-in" mice, which express a protease inactive mutant of nCL-2 instead of wild type nCL-2 under endogenous expression controls. A missense mutation corresponding to the Cys105 to Ser was introduced in the mouse genomic DNA, and neomycin-resistance gene (neoR) flanked by loxP sequences was inserted in the vicinity of the C105S mutation. After homologously targeted mice were obtained, they were crossed with Cre-recombinase expressing transgenic mice to excise neoR, resulting in nCL-2:C105S knock-in mice.
Using these knock-in mice and their tissues, various biochemical, cell-biological, and molecular biological analyses have been performed. As a result, beta-COP, which is one of the subunits of COPI complex functioning in the Golgi-to-ER retrograde membrane trafficking, has been identified as a substrate for nCL-2. Moreover, nCL-2 was shown to localize in the Golgi as in the case of beta-COP. These results strongly suggest that nCL-2 functions in the context of membrane trafficking, which is brand-new concept for mode of action of calpains.

  • Research Products

    (33 results)

All 2006 2005 2004 2003

All Journal Article (32 results) Book (1 results)

  • [Journal Article] Stomach-specific calpain, nCL-2, localizes in mucus cells and proteolyzes the β-subunit of coatomer complex, β-COP.2006

    • Author(s)
      Hata, S.
    • Journal Title

      J. Biol. Chem. (in press)(未定)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Possible functions of p94 in connectin-mediated signaling pathways in skeletal muscle cells.2006

    • Author(s)
      Ojima, K.
    • Journal Title

      J. Muscle Res. Cell Motil. (in press)(未定)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Extracellular production of a heterodimeric protein, neoculin, with sweet-tasting and taste-modifying activities by Aspergillus oryzae.2006

    • Author(s)
      Nakajima, K.
    • Journal Title

      Appl. Environ. Microbiol. (in press)(未定)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Crystal strcture of neoculin : insights into its sweetness and taste-modifying activity.2006

    • Author(s)
      Shimizu-Ibuka, A.
    • Journal Title

      J. Mol. Biol. (in press)(未定)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Extracellular production of a heterodimeric protein, neoculin, with sweet-tasting and taste-modifying activities by Aspergillus oryzae.2006

    • Author(s)
      Nakajima, K., Asakura, T., Maruyama, J., Morita, J., Oike, H., Shimizu-Ibuka, A., Misaka, Misaka, T., Sorimachi, H., Arai, S., Kitamoto, K., Abe, K.
    • Journal Title

      Appl.Environ.Microbiol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Crystal structure of neoculin : insights into its sweetness and taste-modifying activity.2006

    • Author(s)
      Shimizu-Ibuka, A., Morita, Y., Terada, T., Asakura, T., Nakajima, K., Iwata, S., Misaka, T., Sorimachi, H., Arai, S., Abe, K.
    • Journal Title

      J.Mol.Biol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Stomach-specific calpain, nCL-2, localizes in mucus cells and proteolyzes the β-subunit of coatomer complex, β-COP.2006

    • Author(s)
      Hata, S., Koyama, S., Kawahara, H., Doi, N., Maeda, T., Toyama-Sorimachi, N., Abe, K., Suzuki, K., Sorimachi, H.
    • Journal Title

      J Biol.Chem. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Possible functions of p94 in connectin-mediated signaling pathways in skeletal muscle cells.2006

    • Author(s)
      Ojima, K., Ono, Y., Hata, S., Koyama, S., Doi, N., Sorimachi, H.
    • Journal Title

      J.Muscle Res.Cell Motil. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Constitutive activation of the pH-responsive Rim101 pathway in yeast mutants defective in late setps of the MVB/ESCRT pathway.2005

    • Author(s)
      Hayashi, M.
    • Journal Title

      Mol. Cell. Biol. 25

      Pages: 9478-9490

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Inhibitory NK receptor Ly49O is expressed on subsets of dendritic cells in a cellular maturation- and cytokine stimulation-dependent manner.2005

    • Author(s)
      Toyama-Sorimachi, N.
    • Journal Title

      J. Immun. 174

      Pages: 4621-4629

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 神経細胞死の分子機構とCa^<2+>依存性プロテアーゼカルパイン2005

    • Author(s)
      小野 弥子
    • Journal Title

      医学のあゆみ 215・10

      Pages: 811-817

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 「筋弾性タンパク質の国際シンポジウム」報告記2005

    • Author(s)
      尾嶋 孝一
    • Journal Title

      生体の科学 56・2

      Pages: 157-159

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Constitutive activation of the pH-responsive Rim 101 pathway in yeast mutants defective in late steps of the MVB/ESCRT pathway.2005

    • Author(s)
      Hayashi, M., Fukuzawa, T., Sorimachi, H., Maeda, T.
    • Journal Title

      Mol.Cell.Biol. 174

      Pages: 4621-4629

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Inhibitory NK receptor Ly49Q is expressed on subsets of dendritic cells in a cellular maturation- and cytokine stimulation-dependent manner.2005

    • Author(s)
      Toyama-Sorimachi, N., Omatsu, Y., Onoda, A., Tsujimura, Y., Iyoda, T., Maki, A., Sorimachi, H., Dohi, T., Taki, S., Inaba, K., Karasuyama, H.
    • Journal Title

      J.Immun. 25

      Pages: 9478-9490

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Degradation of fodrin by m-calpain in fibroblasts adhering to fibrillar collagen I gel.2004

    • Author(s)
      Sato, K.
    • Journal Title

      J. Biochem. 136

      Pages: 777-785

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Neoculin as a New Taste-modifying Protein Occurring in the Fruit of Curculigo latifolia.2004

    • Author(s)
      Shirasuka, Y.
    • Journal Title

      Biosci. Biotechnol. Biochem. 68

      Pages: 1403-1407

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Induction and myofibrillar targeting of CARP, and suppression of the Nkx2.5 pathway in the MDM mouse with impaired titin-based signaling.2004

    • Author(s)
      Witt, C. C.
    • Journal Title

      J. Mol. Biol. 336

      Pages: 145-154

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Possible regulation of the conventional calpain system by skeletal muscle-specific calpain, p94/calpain 3.2004

    • Author(s)
      Ono, Y.
    • Journal Title

      J. Biol. Chem. 279

      Pages: 2761-2771

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Structure, activation, and biology of calpain.2004

    • Author(s)
      Suzuki, K.
    • Journal Title

      Diabetes 53

      Pages: S12-18

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] カルパインの機能制御と筋ジストロフィー2004

    • Author(s)
      小野 弥子
    • Journal Title

      実験医学 22・2

      Pages: 198-204

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 骨格筋特異的カルパインp94/カルパイン3と肢帯型筋ジストロフィー2004

    • Author(s)
      小野 弥子
    • Journal Title

      ゲノム医学 4・1

      Pages: 27-34

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Calpain.2004

    • Author(s)
      Sorimachi, H., Ono, Y.
    • Journal Title

      in "Encyclopedia of Biological Chemistry" (Elsevier, Oxford; eds., W.J.Lennarz, M.D.Lane) Vol.1

      Pages: 300-306

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Degradation of fodrin by m-calpain in fibroblasts adhering to fibrillar collagen I gel.2004

    • Author(s)
      Sato, K., Hattori, S., Irie, S., Sorimachi, H., Inomata, M., Kawashima, S.
    • Journal Title

      J.Biochem 136

      Pages: 777-785

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Neoculin as a New Taste-modifying Protein Occurring in the Fruit of Curculigo latifolia.2004

    • Author(s)
      Shirasuka, Y., Nakajima, K., Asakura, T., Yamashita, H., Yamamoto, A., Hata, S., Nagata, S., Abo, M., Sorimachi, H., Abe, K.
    • Journal Title

      Biosci.Biotechnol.Biochem. 68

      Pages: 1403-1407

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Induction and myofibrillar targeting of CARP, and suppression of the Nkx2.5 pathway in the MDM mouse with impaired titin-based signaling.2004

    • Author(s)
      Witt, C.C.*, Ono, Y.*, Puschmann, E., McNabb, M., Wu, Y., Gotthardt, M., Witt, S.H., Haak, M., Labeit, D., Gregorio, C.C., Sorimachi, H., Granzier, H., Labeit, S.(*equally contributed first authors)
    • Journal Title

      J.Mol.Biol. 336

      Pages: 145-154

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Possible regulation of the conventional calpain system by skeletal muscle-specific calpain, p94/calpain 3.2004

    • Author(s)
      Ono, Y., Kakinuma, K., Torii, F., Irie, A., Nakagawa, K., Labeit, S., Abe, K., Suzuki, K., Sorimachi, H.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 2761-2771

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Structure, activation, and biology of calpain.2004

    • Author(s)
      Suzuki, K., Hata, S., Kawabata, Y., Sorimachi, H.
    • Journal Title

      Diabetes 53

      Pages: S12-S18

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Newly identified exons encoding novel variants of p94/calpain3 are expressed ubiquitously and overlap the α-glucosidase C gene.2003

    • Author(s)
      Kawabata, Y.
    • Journal Title

      FEBS Lett. 555

      Pages: 623-630

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Heterogeneous nuclear ribonucleoprotein K interacts with and is proteolyzed by calpain in vivo.2003

    • Author(s)
      Kimura, E.
    • Journal Title

      Biosci. Biotechnol. Biochem. 67

      Pages: 1786-1796

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] カルパインと病態-構造活性相関からの考察-2003

    • Author(s)
      反町 洋之
    • Journal Title

      薬理学会誌 122・1

      Pages: 21-29

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Newly identified exons encoding novel variants of p94/calpain3 are expressed ubiquitously and overlap the α-ulucosidase C gene.2003

    • Author(s)
      Kawabata, Y., Hata, S., Ono, Y., Ito, Y., Suzuki, K., Abe, K., Sorimachi, H.
    • Journal Title

      WEBS Lett. 555

      Pages: 623-630

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Heterogeneous nuclear ribonucleoprotein K interacts with and is proteolyzed by calpain in vivo.2003

    • Author(s)
      Kimura, E., Abe, K., Suzuki, K., Sorimachi, H.
    • Journal Title

      Biosci.Biotechnol.Biochem 67

      Pages: 1786-1796

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Encyclopedia of Biological Chemistry, Vol.1, A-D2004

    • Author(s)
      Sorimachi, H.
    • Total Pages
      827
    • Publisher
      Elsevier, Oxford (eds., W.J. Lennarz and M.D. Lane)
    • Description
      「研究成果報告書概要(和文)」より

URL: 

Published: 2007-12-13  

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