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Intracellular transport and molecular chaperone

Research Project

Project/Area Number 15390087
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionChiba University

Principal Investigator

AOE Tomohiko  Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (90311612)

Co-Investigator(Kenkyū-buntansha) SHINOZUKA Norihiro  Chiba University, Graduate School of Medicine, Research Associate, 大学院・医学研究院, 助手 (80261907)
青野 光夫  千葉大学, 医学部附属病院, 助手 (40292693)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2005: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥6,400,000 (Direct Cost: ¥6,400,000)
Keywordsendoplasmic reticulum / ER stress / KDEL receptor / Golgi / 小胞体ストッレス
Research Abstract

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) evokes the ER stress response. The resultant outcomes are cytoprotective, but also pro-apoptotic. ER chaperones and misfolded proteins exit to the secretory pathway and are retrieved to the ER, during which process the KDEL receptor plays a significant role. Using an expression of a mutant KDEL receptor that lacks the ability for ligand recognition, we show that the impairment of retrieval by the KDEL receptor led to a mis-sorting of BiP, an ER chaperone that has a retrieval signal from the early secretory pathway, which induced intense ER stress response and an increase in susceptibility to ER stress in HeLa cells. Furthermore, we show that the ER stress response accompanied the activation of p38 MAP kinases and c-Jun amino-terminal kinases (JNKs) and that the expression of the mutant KDEL receptor suppressed the activation of p38 and JNK1 not JNK2. The effect of the expression of the mutant KDEL receptor was consistent with the effect of a specific inhibitor for p38 MAP kinases, since the inhibitor sensitized HeLa cells to ER stress. We also found that the activation of the KDEL receptor by the ligand induced the phosphorylation of p38 MAP kinases. These results indicate that the KDEL receptor participates in the ER stress response not only by its retrieval ability but also by modulating MAP kinase signalling, which may affect the outcomes of the mammalian ER stress response.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (13 results)

All 2005 2004 2003 Other

All Journal Article (12 results) Publications (1 results)

  • [Journal Article] Analgesic effects of nonsteroidal antiinflammatory drugs, acetaminophen, and morphine in a mouse model of bone cancer pain.2005

    • Author(s)
      Saito O, Aoe T, Yamamoto T
    • Journal Title

      J Anesth. 19(3)

      Pages: 218-24

    • NAID

      10016650380

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Analgesic effects of nonsteroidal antiinflammatory drugs, acetaminophen, and morphine in a mouse model of bone cancer pain.2005

    • Author(s)
      Saito O, Aoe T, Yamamoto T.
    • Journal Title

      J Anesth. 19(3)

      Pages: 218-224

    • NAID

      10016650380

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Dilated Cardiomyopathy Caused by Aberrant Endoplasmic Reticulum Quality Control in Mutant KDEL Receptor Transgenic Mice.2004

    • Author(s)
      Hamada H, Suzuki M, Yuasa S, Mimura N, Shinozouka N, Takada Y, Suzuki M, Nishino T, Nakaya H, Koseki H, Aoe T
    • Journal Title

      Mol Cell Biol. Sep:24(18)

      Pages: 8007-17

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Reduction of SNAP25 in acid secretion defect of Foxl1-/- gastric parietal cells.2004

    • Author(s)
      Kato Y, Fukamachi H, Takano-Maruyama M, Aoe T, Murahashi Y, Horie S, Suzuki Y, Saito Y, Koseki H, Ohno H
    • Journal Title

      Biochem Biophys Res Commun. 320(3)

      Pages: 766-72

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Dilated Cardiomyopathy Caused by Aberrant Endoplasmic Reticulum Quality Control in Mutant KDEL Receptor Transgenic Mice.2004

    • Author(s)
      Hamada H, Suzuki M, Yuasa S, Mimura N, Shinozuka N, Takada Y, Suzuki M, Nishino T, Nakaya H, Koseki H, Aoe T.
    • Journal Title

      Mol Cell Biol. Sep;24(18)

      Pages: 8007-8017

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Reduction of SNAP25 in acid secretion defect of Fox11-/- gastric parietal cells.2004

    • Author(s)
      Kato Y, Fukamachi H, Takano-Maruyama M, Aoe T, Murahashi Y, Horie S, Suzuki Y, Saito Y, Koseki H, Ohno H.
    • Journal Title

      Biochem Biophys Res Commun. 320(3)

      Pages: 766-772

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Reduction of SNAP25 in acid secretion defect of Foxl1-/- gastric parietal cells.2004

    • Author(s)
      Kato Y, Fukamachi H, Takano-Maruyama M, Aoe T, Murahashi Y, Horie S, Suzuki Y, Saito Y, Koseki H, Ohno H.
    • Journal Title

      Biochem Biophys Res Commun. 320

      Pages: 766-772

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Dilated Cardiomyopathy Caused by Aberrant Endoplasmic Reticulum Quality Control in Mutant KDEL Receptor Transgenic Mice.2004

    • Author(s)
      Hamada H, Suzuki M, Yuasa S, Mimura N, Shinozuka N, Takada Y, Suzuki M, Nishino T, Nakaya H, Koseki H, Aoe T.
    • Journal Title

      Mol Cell Biol. 24

      Pages: 8007-8017

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The KDEL receptor modulates the endoplasmic reticulum stress response through MAP kinase signaling cascades.2003

    • Author(s)
      Yamamoto, K., Hamada, H., Shinkai, H., Kohno, Y., Koseki, H., Aoe, T.
    • Journal Title

      J. Biol. Chem. 278(36)

      Pages: 766-72

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Aniti-mechanical allodynic effect of intrathecal and intracerebroventricular injection of orexin-A in the rat neuropathic pain model.2003

    • Author(s)
      Yamamoto, K., Saito, O., Shono, K., Aoe, T., Chiba, T
    • Journal Title

      Neurosci. Lett. 347(3)

      Pages: 183-186

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Anti-mechanical allodynic effect of intrathecal and intracerebroventricular injection of orexin-A in the rat neuropathic pain model.2003

    • Author(s)
      Yamamoto, T., Saito, O., Shono, K., Aoe, T., Chiba, T.
    • Journal Title

      Neurosci.Lett. 347(3)

      Pages: 183-186

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The KDEL receptor modulates the endoplasmic reticulum stress response through MAP kinase signaling cascades.2003

    • Author(s)
      Yamamoto, K., Hamada, H., Shinkai, H., Kohno, Y., Koseki, H., Aoe, T.
    • Journal Title

      J.Biol.Chem. 278(36)

      Pages: 766-772

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] Yamamoto, K., Hamada, H., Shinkai, H., Kohno, Y., Koseki, H., Aoe, T.: "The KDEL receptor modulates the endoplasmic reticulum stress response through MAP kinase signaling cascades."J Biol Chem.. 278. 34525-32 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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