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Studies of dystrophin and its associated proteins

Research Project

Project/Area Number 02454160
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Pathological medical chemistry
Research InstitutionNational Institute of Neuroscience

Principal Investigator

OZAWA Eijirou  National Institute of Neuroscience National Center of Neurology and Psychiatry Department of Cell Biology Head, Chairman, 神経研究所・機能研究部 (20014178)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Hideko  National Institute of Neuroscience National Center of Neurology and Psychiatry D, 機能研究部, 流動研究員
MIZUNO Yuji  National Institute of Neuroscience National Center of Neurology and Psychiatry D, 機能研究部, 流動研究員
SUZUKI Atsushi  National Institute of Neuroscience National Center of Neurology and Psychiatry D, 機能研究部, 併任研究員
HAGIWARA Yasuko  National Institute of Neuroscience National Center of Neurology and Psychiatry D, 機能研究部, 室長 (00175530)
YOSHIDA Mikiharu  National Institute of Neuroscience National Center of Neurology and Psychiatry D, 機能研究部, 室長 (70111151)
林 謙介  国立精神神経センター, 神経研究所・機能研究部, 研究員 (50218567)
田中 光  国立精神神経センター神経研究所, 機能研究部, 流動研究員
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1992: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1991: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1990: ¥3,600,000 (Direct Cost: ¥3,600,000)
KeywordsMuscular Dystrophy / Dystrophin / Utrophin / Glycoprotein Complex / 筋シストロフィー / 筋ジストロフィ- / ジストロフィン関連タンパク質
Research Abstract

Dystrophin is the responsible protein of Duchenne muscular dystrophy (DMD). We purified dystrophin and its associated proteins, raised their antibodies and studied the molecular pathophysiology of DMD in terms of these proteins.
Dystrophin purified from rabbit skeletal muscles carries several kinds of proteins, some of which are glycoproteins. We determined the molar ratio of these binding proteins to dystrophin. We digested dystrophin with calpain to analyze its enzyme-accessible sites.
Among the dystrophin binding proteins, glycoproteins A2, A3 and A4 have been reported forming a complex called glycoprotein complex (GPC). We found that GPC bound to the cysteine-rich domain and the first half of the C-terminal domain of dystrophin. This site has been reported, when missing, to give rise to sever phenotype of the disease, namely, DMD. On these basis, we conclude that the loss of interaction between dystrophin and GPC. The amino acid sequence of GPC binding site is highly homologous to that of corresponding site of utrophin, an isoform of dystorphin. Therefore, it is highly possible that GPC can bind also to utrophin at the corresponding site.
Further, we examined DMD muscles histochemically and with immunoblot analysis, and found that utrophin was fairly heavily expressed in place of dystrophin which was missing, A2 and A3 were reduced but distinctly present. This show keen contrast to the reports of Campbell's group. Based on our results, we tentatively conclude that utrophin is expressed to replace in DMD muscles, and binds to GPC but the disease progressed probably due to its low abundance of expression.

Report

(4 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] 吉田 幹晴,小沢 えい二郎: "Glycoprotein complex anchoring dystrophin to sarcolemma" Journal of Biochemistry. 108. 748-752 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 田中 光,小沢 えい二郎: "Expression of dystrophin mRNA and the protein in the developing rat heart" Biochem,Biophys.Res.Comm.172. 824-829 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 田中 光,石黒 恒男,江口 新比古,斎藤 加代子,小沢 えい二郎: "Expression of a dystrophin-related protein associated with the skeletal muscle cell membrane" Histochemistry. 96. 1-5 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 小沢 えい二郎,吉田 幹晴,萩原 康子,田中 光,林 謙介,池谷 紀代子: "Formation of dystrophin lining on muscle cell membrane in myogenesis in vivo" Frontiers in muscle research. 305-319 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 田中 光,林 謙介,小沢 えい二郎: "Positive immunostaining with dystrophin antibodies in mdx skeletal muscle" Proceedings of the Japan Academy. 67. 148-152 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 池谷 紀代子,斉藤 加代子,林 謙介,田中 光,萩原 康子,吉田 幹晴,山内 朱美,福山 幸夫,石黒 恒男,江口 新比古,小沢 えい二郎: "Molecular genetic and immunohistochemical analysis of dystrophin of a young patient with X-linked muscular dystrophy" American Journal of Medical Genetics. 43. 580-587 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Eijiro Ozawa, Mikiharu Yoshida: "Glycoprotein complex anchoring dystrophin to sarcolemma" Journal of Biochemistry. 108. 748-752 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hikaru Tanaka, Eijiro Ozawa: "Expression of dystrophin mRNA and the protein in the developing rat heart" Biochem. Biophys. Res. Comm.172. 824-829 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hikaru Tanaka, Tsuneo Ishiguro, Chikahiko Eguchi, Kayoko Saito, Eijiro Ozawa: "Expression of a dystrophin-related protein associated with the skeletal muscle cell membrane" Histochemistry. 96. 1-5 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Eijiro Ozawa, Mikiharu Yoshida, Yasuko Hagiwara, Hikaru Tanaka, Kensuke Hayashi, Kiyoko Ikeya: "Formation of dystrophin lining on muscle cell membrane in myogensis in vivo" Frontiers in muscle research. 305-319 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hikaru Tanaka, Kensuke Hayashi, Eijiro Ozawa: "Positive immunostaining with dystrophin antibodies in mdx skeletal muscle" Proceedings of the Japan Academy. 67. 148-152 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kiyoko Ikeya, Kayoko Saito, Kensuke Hayashi, Hikaru Tanaka, Yasuko Hgiwara, Mikiharu Yoshida, Akemi Yamauchi, Yikio Fukuyama, Tsuneo Ishiguro, Chikahiko Eguchi, Eijiro Ozawa: "Molecular genetic and immunohistochemical analysis of dystrophin of a young patient with X-linked muscular dystrophy" American Journal of Medical Genetics. 43. 580-587 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Atsushi Suzuki, Mikiharu Yoshida, Hideko Yamamoto, Eijiro Ozawa: "Glycoprotein-binding site of dystrophin is confined to the cysteine-rich donain and the first half of the carboxy-terminal domain" FEBS letters. 308. 154-160 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Mikiharu Yoshida, Atsushi Suzuki, Teruo Shimizu, Eijiro Ozawa: "Proteinase-sensitive sites on isolated rabbit dystrophin" Journal of Biochemistry. 112. 433-439 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Toshikazu Masuda, Noboru Fujimaki, Eijiro Ozawa, Harunori Ishikawa: "Confocal laser microscopy of dystrophin localization in guinea pig skeletal muscle fibers" Journal of Cell Biology. 119. 543-548 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yuji Mizuno, Ikuya Nonaka, Shunsaku Hirai, Eijiro Ozawa: "Reciprocal expression of dystrophin and dystrophin-related protein (DRP) in muscles of Duchenne muscular dystrophy patients female DMD-carriers and control subjects" Journal of the Neurological Sciences.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hideko Yamamoto, Yasuko Hagiwara, Yuji Mizuno, Mikiharu Yoshida, Eijiro Ozawa: "Heterogeneity of dystrophin associated proteins in muscles from patients with Duchenne muscular dystrophy"

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yuji Mizuno, Mikiharu Yoshida, Ikuya Nonaka, Shunsaku Hirai, Eijiro Ozawa: "Expression of utrophin (dystrophin related protein) and dystrophin-associated glycoproteins in muscles from patients with Duchenne muscular dystrophy"

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 鈴木 厚,吉田 幹晴 山本 秀子,小沢 〓二郎: "Glycoprotein-binding site of dystrophin is confined to the cysteine-rich domain and the first half of the carboxy-terminal domain" FEBS letters. 308. 154-160 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 吉田 幹晴,鈴木 厚 清水 輝夫,小沢 〓二郎: "Proteinase-sensitive sites on isolated rabbit dystrophin" Journal of Biochemistry. 112. 433-439 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 増田 俊和,藤巻 昇 小沢 〓二郎,石川 春律: "Confocal laser microscopy of dystrophin localization in guinea pig skeletal muscle fibers" Journal of Cell Biology. 119. 543-548 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 水野 裕司,埜中 征哉 平井 俊策,小沢 〓二郎: "Reciprocal expression of dystrophin and dystrophin-related protein (DRP) in muscles of Duchenne muscular dystrophy patients female DMD-carriers and control subjects" Journal of the Neurological Sciences.

    • Related Report
      1992 Annual Research Report
  • [Publications] 田中 光,石黒 恒男,江口 新比古,斎藤 加代子,小沢 〓二郎: "Expression of a dystrophinーrelated protein associated with the skeletal muscle cell membrane" Histochemistry. 96. 1-5 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 小沢 〓二郎,吉田 幹晴,萩原 康子,田中 光,林 謙介,池谷 紀代子: "Formation of dystrophin lining on muscle cell membrane in myogenesis in vivo" Frontiers in muscle research. 305-319 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 田中 光,林 謙介,小沢 〓二郎: "Positive immunostaining with dystrophin antibodies in mdx skeletal muscle" Proceedings of the Japan Academy. 67. 148-152 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 池谷 紀代子,斎藤 加代子,林 謙介,田中 光,萩原 康子,吉田 幹晴,山内 朱美,福山 幸夫,石黒 恒男,江口 新比古,小沢 〓二郎: "Molecular genetic and immunohistochemical analysis of dystrophin of a young patient with Xーlinked muscular dystrophy" American Journal of Medical Genetics.

    • Related Report
      1991 Annual Research Report
  • [Publications] 鈴木 厚,吉田 幹晴,小沢 〓二郎: "Glycoproteinーbinding site of dystrophin is cofined to the cysteineーrich domain and the first half of the carboxyーterminal domain"

    • Related Report
      1991 Annual Research Report
  • [Publications] 吉田 幹晴,鈴木 厚,小沢 〓二郎: "Analysis of molecular structure of dystrophin"

    • Related Report
      1991 Annual Research Report
  • [Publications] 吉田 幹晴,小沢 〓二郎: "Glycoprotein complex anchoring dystrophin to sarcolemma" Journal of Biochemistry. 108. 748-752 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 田中 光,小沢 〓二郎: "Expression of dystrophin mRNA and the protein in the developing rat heart" Biochem.Biophys.Res.Comm.172. 824-829 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 田中 光,石黒 恒男,江口 新比古,斎藤 加代子,小沢 〓二郎: "Expression of a dystrophinーrelated protein associated with the skeletal muscle cell membrane" Histochemistry.

    • Related Report
      1990 Annual Research Report
  • [Publications] 池谷 紀代子,斎藤 加代子,林 謙介,田中 光,萩原 康子,吉田 幹晴,山内 朱美,福田 幸夫,石黒 恒男,江口 新比古 小川 〓二郎: "Molesular genetic and immunohistochemical analysis of dystrophin of a young patient with Xーlinked muscular dysrophy"

    • Related Report
      1990 Annual Research Report
  • [Publications] 吉田 幹晴,萩原 康子,小沢 〓二郎: "Immunopeptide map of dystrophin"

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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