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Structure and function of ryanodine receptors

Research Project

Project/Area Number 09470022
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionThe University of Tokyo

Principal Investigator

TAKESHIMA Hiroshi  The University of Tokyo, Graduated School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (70212024)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 1998: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1997: ¥9,000,000 (Direct Cost: ¥9,000,000)
KeywordsCa^<2+> release channel / ryanodine receptor / intracellular Ca^<2+> / caffeine / muscle contraction / 筋収縮 / Ca^<2+>放出チャネル / カルシウム放出チャネル / カルシウム・ストア / カフェイン
Research Abstract

The structure-function relationship of ryanodine receptor subtypes (namely, RyR-l, 2 and 3) have been investigated by means of molecular biological and genetic methords, for example in vitro mutagenesis and generation of knockout mice. Our major findings in this research project are listed below.
1. Generation and characterization of mutant mice lacking RyR-2. Because function of RyR-2 was unknown in embryonic heart, we have generated mutant mice lacking RyR-2. The results in the mutant mice showed non-essential function of RyR-2 for contraction of embryonic cardiac muscle cells, however, the RyR-2-deficient mice exhibiting cardiac arrest die around embryonic day 10. Our results obtained indicate that RyR-2 is essential for the maintenance of intracellular Ca^<2+> stores by regulating luminal resting Ca^<2+> levels in embryonic cardiac muscle cells.
2. Intramolecular functional regions on the primary structure of the ryanodine receptor. We have mapped a region critical for skeletal muscle excitation-contraction coupling to the called D2 region on the RyR-1 molecule in our cDNA expression system using RyRs-deficient muscle. By combination of cDNA expression and single channel measurement, we have located the Ca^<2+> release channel-forming domain and a portion (designated as D3 region) responsible for Ca^<2+> binding for channel inactivation on the RyR-1 molecule.
3. Identification of novel proteins localized in skeletal muscle triad junction. We have identified mitsugumin29 (MG29) and MG23 as novel transmembrane proteins from skeletal muscle the triad junction by isolating specific monoclonal antibodies and cloning cDNAs. MG29 was shown to be a novel member of the synaptophysin family, suggesting that the presynaptic region and triad junction share evolutionally related components.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (37 results)

All Other

All Publications (37 results)

  • [Publications] 山沢 他3名: "A region of the ryanodine receptor critical for excitation-coutraction coupling in skeletal muscle." J.Biol.Chen.272. 8161-8164 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 池本 他6名: "Fanctional and worplological features of myocytes from unutaint mice lacking bath ryanodine receptors type 1 and type 3." J.Physiol.501. 305-312 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 竹島 他7名: "Mitsuganin 2P, a uovel syuaptophysin family member from the friad junction in skolotal muscle." Biochem.J.331. 317-32〓 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 竹島 他5名: "Embvyoic lethality and abnormal cardiac myocytes in mice Cacking ryanodine receptor type 2." EMBO J.17. 3309-3316 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 志牟田 他5名: "Structure and expression of mitsugnmin 29 pane" FEBS Lett.431. 263-267 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 西 他4名: "Mitsugumin 23, a novel transmeiubrane plotain on endoplasuic reticulum and nuclear momdranes" FEBS Lett.432. 191-196 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamazawa, T., Takeshima, H., Shimuta, M.& Iino, M.: "A region of the ryanodine receptor critical for excitation-contraction coupling in skeletal muscle." J.Biol.Chem.272. 8161-8164 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishi, M., Houtani, T., Sato, K., Doi, T., Noda, Y., Mamiya, T., Kuno, J., Takeshima, H., Nukada, T., Nabeshima, T., Yamashita, T., Noda, T.& Sugimoto, T.: "Unrestrained nociceptive response and disregulation of hearing ability in mice lacking nociceptin/orphaninFQ receptor." EMBOJ.16. 1858-1864 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ikemoto, T., Komazaki, S., Takeshima, H., Nishi, M., Noda, T., Iino, M.& Endo, M.: "Functional and morphological features of myocytes from mutant mice lacking both ryanodine receptors type 1 and type 3." J.Physiol.501. 305-312 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Suda, N., Franzius, D., Fleig, A., Nishimura, S., Bodding, M., Hoth, M., Takeshima, H.& Penner, R.: "Ca^<2+>-induced Ca^<2+> release in chinese hamster ovary (CHO) cells co-expressing dihydropyridine and ryanodine receptors." J.Gen.Physiol.109. 619-631 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Bhat, M.B., Zhao, J., Hayek, S., Freeman, E.C., Takeshima, H.& Ma, J.: "Deletion of amino acids 1641-2437 from the foot region of skeletal muscle ryanodine receptor alters the conduction properties of the Ca release channel." Biophys.J.73. 1320-1328 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Bhat, M.B., Zhao, J., Takeshima, H.& Ma, J.: "Functional Calcium release channel formed by the carboxyl-terminal portion of ryanodine receptor." Biophys.J.73. 1329-1336 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Bhat, M.B., Zhao, J., Zang, W., Balke, W., Takeshima, H., Wier, W.G.& Ma, J.: "Caffeine-induced Ca^<2+> release from chinese hamster ovary cells expressing muscle ryanodine receptor.Effects on full-lenght and carboxyl-terminal portion of Ca^<2+> release channel." J.Gen.Physiol.110. 749-762 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ueda, H., Yamaguchi, T., Tokuyama, S., Inoue, M., Nishi, M.& Takeshima, H.: "Partial loss of tolerance liability to morphine analgesia in mice lacking the nociceptin receptor gene." Neurosci.Lett.237. 136-138 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mamiya, T., Noda, Y., Nishi, M., Takeshima, H.& Nabeshima, T.: "Enhancement of spatial attention in nociceptin receptor-knockout mice." Brain Res.783. 236-240 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshima, H., Shimuta, M., Komazaki, S., Ohmi, K., Nishi, M., Iino, M., Miyata, A.& Kangawa, K.: "Mitsugumin29, a novel synaptophysin family member from the triad junction in skeletal muscle." Biochem.J.331. 317-322 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshima, H., Komazaki, S., Hirose, K., Nishi, M., Noda, T.& Iino, M.: "Embryonic lethality and abnormal cardiac myocytes in mice lacking ryanodine receptor type 2." EMBOJ.17. 3309-3316 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Noda, Y., Mamiya, T., Nabeshima, T., Nishi, M.Higashioka, M.& Takeshima, H.: "Loss of antinociception induced by naloxone benzoylhydrazone in nociceptin receptor-knockout mice." J.Biol.Chem.275. 18047-18051 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Manabe, T., Noda, Y., Mamiya, T., Katagiri, H., Houtani, T., Nishi, M., Noda, T., Takahashi, T., Sugimoto, T., Nabeshima, T.& Takeshima, H.: "Facilitation of long-term potentiation and memory in mice lacking nociceptin receptor." Nature. 394. 577-581 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shimura, M., Komazaki, S., Nishi, M., Iino, M., Nakagawara, K & Takeshima, H.: "Structure and expression of mitsugumin29 gene." FEBS Lett.431. 263-267 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nishi, M., Komazaki, S., Iino, M., Kangawa, K.& Takeshima, H.: "Mitsugumin23, a novel transmembrane protein on endoplasmic reticulum and nuclear membranes." FEBS Lett.432. 191-196 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Komazaki, S., Ikemoto, T., Takeshima, H., Iino, M., Endo, M.& Nakamura, H.: "Morphological abnormalities of adrenal grand and hypertrophy of liver in mutant mice lacking ryanodine receptors." Cell Tissue Res.294. 467-473 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ikemoto, T., Takeshima, H., Iino, M.& Endo, M.: "Effect of calmodulin on Ca^<2+>-induced Ca^<2+> release of skeletal muscle from mutant mice expressing either ryanodine receptor type 1 or type 3." Pflugers Arch.437. 43-48 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 間宮 他4名: "Enhencemect of spetial attention in nociceptin receptor-knockout mice" Brain Res.783. 236-240 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 野田 他5名: "Loss of autinociception induced by naloxoue benzoylhydrazone in nociceptin receptor-knockout mice" J.Biol.Chem.275. 18047-18051 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 真鍋 他10名: "Facilitation of long-term potentiation and memory in mice lacking nociceptin receptors." Nature. 394. 577-581 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 竹島 他7名: "Mitsugamin 29,a novel synaptophysin family member from the triad junction in skeletal muscle" Biochem,J.331. 317-322 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 竹島 他5名: "Embryonic lethality and abnormal cardiac myocytes in mice lacking ryanodine receptor type2." EMBO J.17. 3309-3316 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 志牟田 他5名: "Stracture and expression of witsugamin 29 gene" FEBS Lett.431. 263-267 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamazawa 他3名: "A region of the uyanodire receptor critical for excitation-contraction coupling in skeletal muscle" J.Biol.Chem.272. 8161-8164 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nishi 他12名: "Ourestrained uociceptive response and disregulation of heaving ability in mice lacking uociceptin/orphaninFQ receptor" EMBO J.16. 1858-1864 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ikemoto 他6名: "Functional and morphological features of myocytes from mutant mice lacking both ryanodine receptor type1 and type3" J.Physiol.501. 305-312 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Suda 他7名: "Ca^<2+>-induced Ca^<2+> release in chinese hamstar overy cells CO-expressing dihydropyridive and uyanodine receptors" J.Gen.Physiol.109. 619-631 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Bhat 他5名: "Deletion of amino acid 1641-2437 from the foot region of skeletal muscle ryanodive receptor atters the conduction properties of Ca release channel" Biophysi J. 73. 1320-1328 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Bhat 他3名: "Functional calcium release chamel formed by the carboxyl-terminal portion of rysnodine receptor" Biophys.J. 73. 1329-1336 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 黒川ら: "ノックアウトマウス・データブック" 中山書店, 564 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 芳賀ら: "脳における情報伝達" 共立出版株式会社, 608 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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