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1997 Fiscal Year Final Research Report Summary

Isolation of signal molecules on the secretion of amyloid precursor

Research Project

Project/Area Number 08458259
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neuroscience in general
Research InstitutionThe University of Tokyo

Principal Investigator

ISHIURA Shoichi  The University of Tokyo, Institute of Molecular and Cellular Biosciences, Associate Professor, 分子細胞生物学研究所, 助教授 (10158743)

Co-Investigator(Kenkyū-buntansha) SORIMACHI Hiroyuki  The University of Tokyo, Institute of Molecular and Cellular Biosciences, Assist, 分子細胞生物学研究所, 助手 (10211327)
Project Period (FY) 1996 – 1997
KeywordsAlzheimer's disease / Amyloid / Protease / Signal molecules / Processing / Secretion
Research Abstract

Alzheimer's disease amyloid precursor protein (APP) has attracted attention due to its involvement in the deposition of amyloid beta protein found in brain of both sporadic and genetic Alzheimer's disease patients. It is accepted that APP undergoes tow different types of processing catalyzed by three hypothesized proteases. One type mediated by alpha-secretase involves the non-amyloidogenic pathway, which precludes the generation of the beta protein. The N-terminal large fragment of APP is secreted into serum.
The intracellular sorting of APP has attracted much interest, because some sorting signals in APP molecule are highly involved in the fate of newly-synthesized APP.We constracted two mutants, APPE19 and APPdeltaC10, which contains or deletes an endoplasmic reticulum (ER) retention signal. Addition of ER retention signal inhibied secretion of APP,while deletion of it promoted secretion. These results suggest that these sequences are important for the secretion and intracellular metabolism of APP.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Ishiura, S.: "Alzheimers disease and proteinases" in Proteases(V.Turk ed.). (印刷中). (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishiura, S.et al.: "Proteases involved in the processing of the Alzheimers disease amyloid precursor protein" in Proteilysis in Cell Function. 507-512 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ono, Y. et al.: "Deletion of an endosomal/lysosor al targetsignal pramstes the secetion of Alzhiemers desiase amyloid Precursor proteir(APP)" J.Biochim.121. 585-590 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Lee, H-J.et al: "Molecular cloning and characterization of a novel tissue specific Calpain prodominanty expressed in the digestive tract." Comp,Biochem.Biophys.118B. 539-547 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kinbara, K.et al.: "Muscle specific calpair,p94,interacts with the extreme C-terminal region of connectir,a unigue region franked by two IgC_2 motifs." Arch.Biochem.Biophys. 342. 99-107 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sorimachi, H. et al.: "Tissue-specific expression and α-actinin binding proterties of the Z-disstitin." J.Mol.Biol. 270. 688-695 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishiura, S.: "Alzheimer's disease and proteinases." in Proteases (V.Turk, ed.) Birkhauser Verlag AG,Basel. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishiura.S., Mabuchi, Y., Urakami-Manaka, Y., Isobe, K., Tagawa, K., Maruyama, K., Sorimachi, H.& Suzuki, K.: "Proteases involved in the processing of the Alzheimer's disease amyloid prcursor protein." in Proteolysis in Cell Functions (V.K.Hopsu-Have, ed.) ISO Press, Amsterdam.507-512 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ono, Y., Kinouchi, T., Sorimachi, H., Ishiura, S.& Suzuki, K: "Deletion of an endosomal/lysosomal target in signal promotes the secretion of Alzheimer's disease amyloid precursor protein (APP)." J.Biochem.121. 585-590 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Jeong, S.-Y., Sorimachi, H., Lee, H.-J., Ishiura, S.and Suzuki, K.: "Molecular cloning and characterization of cDNA for the mu-type calpain large subunit and the small subunit of chicken calpain." Comp.Biochem.Giophys.118B. 539-547 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kinbara, K., Sorimachi, H., Ishiura, S.and Suzuki, K.: "Muscle-specific calpain, p94, interacts with the extreme C-terminal region of connectin, a unique region franked by two immunoglobulin C2 motifs" Arch.Biochem.Biophys.342. 99-107 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sorimachi, H., Freigurg, A., Kolmerer, B., Ishiura.S., Stier, G., Gregorio, C.C., Labeit, D., Linke, W.A., Suzuki, K.and Labeit, S.: "Tissue-specific expression and alpha-actinin binding properties of the Z-disc titin : implications for the nature of vertebrate Z-discs." J.Mol.Biol.270. 688-695 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-16  

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