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Elucidation of secretory mechanism at molecular level

Research Project

Project/Area Number 03454144
Research Category

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

Allocation TypeSingle-year Grants
Research Field General pharmacology
Research InstitutionUniversity of Tokyo

Principal Investigator

NONOMURA Yoshiaki  Univ.Tokyo, Fac.Med., Dept.Pharmacal., Professor, 医学部(医), 教授 (80009993)

Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1993: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1992: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1991: ¥3,300,000 (Direct Cost: ¥3,300,000)
KeywordsGelsolin family / 74KDa protein / Exocytic secretion / Wortmannin / Myosin light chain kinase / PC-12 cell / Dopamine release / Myosin actin interaction / ミオシン軽鎖キーゼ / P_2レセプター / ゲルゾリンファミリー74KD / ミオシン軽鎮キナーゼ / オルトマンニン / クロマフィン細胞 / RBL細胞 / 血小板 / Ca^<2+>流入 / ミオシン / アクチン / ミオシン軽鎖キナ-ゼ / クロマフイン細胞 / Wartmannin / 74KD蛋白質
Research Abstract

We have studied the mechanism of exocytic secretion at molecular level for several years, especially to focus one of the gelsolin family, 74KDa protein. On the basis of this study we have clarified an important role of myosin actin interaction. 74KDa existed in endocrine and neuronal cells which secreted hormones and neurotransmitter exocytically. We determined whole amino acid sequence of 74kDa utilizing PCR method.
On the other hand, using wortmannin, a specific MLCK inhibitor and antibody of non muscle myosin heavy chain as excellent tools, we found that myosin-actin interaction functioned in exocytosis in many cells. Particularly in primary cultured cell of sympathtic ganglion myosin-actin seemed to act in release of acetylcholine by electrical stimulation. In PC-12 cell myosin and actin moved at the same position by ATP stimulation during the short time when dopamine was released.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Sakurai,T.,Kurokawa,H.and Nonomura,Y.: "The Ca^<2+>-dependent actin filament-severing activity of 74KDa protein resides in its NH_2-terminal half" Journal of Biological Chemistry. 266. 4581-4585 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sakurai,T.,Kurokawa,H.and Nonomura,Y.: "Comparison between the gelsolin and adseverine domain structure" Journal of Biological Chemistry. 266. 15979-15983 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sakurai,T.,Ohmi,K.and Nonomura,Y.: "A new Ca^<2+>-dependent actin filament-severing protein in adrenal medulla" Biomedical Research. 12. 179-180 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kitani,S.,Teshiwa,R.…Matsuda,Y.and Nonomura,Y.: "Inhibition of IgE-mediated histamine release by myosin light chain Kinase inhibitor" Biochemical & Biophysical Research Communications. 183. 48-54 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nakanishi,S.,Kakita,S.…Hashimoto,Y.& Nonomura,Y.: "Wortmannin,a microbial product inhibitor of myosin light chain Kinase" Journal of Biological Chemistry. 267. 2157-2163 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hashimoto,Y.,Ogihara,A.…Kurokawa,K.& Nonomura,Y.: "Two thrombin-activated Ca^<2+>-channels in human platelete" Journal Biological Chemistry. 267. 17078-17081 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sakurai, T., Kurokawa, H.& Nonomura, Y.: "The Ca^<2+>-dependent actin filament-severing activity of 74-kDa protein (Adseverin) resides in its NH_2-terminal half" J.Biol.Chem.266(7). 4581 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sakurai, T., Kurokawa, H.& Nonomura, Y.: "Comparison between the gelsolin and adseverin domain structure" J.Biol.Chem.266(24). 15979-15983 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sakurai, T., Ohmi, K.& Nonomura, Y.: "A new Ca^<2+>-dependent action filament-severing protein in adrenal medulla" Biomed.Res.12. 179-180 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kitani, S., Teshima, R., Morita, Y., Ito, K., Matsuda, Y.& Nonomura, Y.: "Inhibition of IgE-mediated histamine release by myosin light chain kinase inhibitors" Biochem.Biophys.Res.Comm.183(1). 48-54 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nakanishi, S., Kakita, S.Takahashi, I., Kawahara, K., Tsukuda, E., Sano, T., Yamada, K., Yoshida, M., Kase, H., Matsuda, Y., Hashimoto, Y.& Nonomura, Y.: "Wortmannin, a microbial product inhibitor of myosin light chain kinase" J.Biol Chem.267(4). 2157-2163 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hashimoto. Y., Ogihara, A., Nakanishi, S., Matsuda. Y., Kurokawa, K.and Nonomura, Y.: "Two thrombin-activated Ca^<2+> channels in human platelets" J.Biol.Chem.267(24). 17078-17081 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yuno,H.…Nonomura,Y.& Matsuda,Y.: "Inhibition of histamine secretion by wortmannin through the black of phosphatidylinositol 3-Kinase in RBL-2H3 cells" Journal of Biological Chemistry. 268. 1-11 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nonomura,Y.: "Multifunctional role of myosin molecules in various Kinds of cells" Biomedical Research. 14. 107-112 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ohmi,K.,Yamashita,S.,Hashimoto,Y.& Nonomura,Y.: "Induction of giant endothelial cell in culture by K-252a,a protein Kinase in hibitor" Japanese Journal of Pharmacology. 63. 195-202 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nakayama,H.,…Nonomura,Y.& Kurokawa,Y.: "A topological study of the electroplax sodium channel with site-directed antibodies" Biochim Biophysic Acta. 1145. 130-140 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nakamura,S.Sakurai,T.& Nonomura,Y.: "Differential expression of bovine adseverine in adrenal gland revealed by in situ bybridization" Journal of Biological Chemistry. (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 野々村禎昭.祖父江憲治: "新生化学実験法講座10“血管-内皮と平滑筋"" 東京化学同人・東京, 497 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] S.Kitani,……& Y.Nonomura: "Inhibition of IgE mediated histumine r elease of myosin lighr chain kinuse inhibitors" Biochem.Biophys.Res.Comm.183. 48-54 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Nakanishi,……& Y.Nonomura: "Wortmannin,a microbial inhibitor of myosin light chain kinase" J.Biol.Chem.267. 2157-2163 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.Banno,……Y.Nonomura,& Y.Nozawa: "Ettoots of gelsolin on human plateleti ytosol phospho-inositide-phospholipase C isogymes" J. Biol. Chem.267. 6488-6494 (1922)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Ohara-Imaizumi Y.Nonomura,& K.Kumakura: "Inhibition of Ca^<2+> dependent catecholamine release by myosin light chain Kinash inhibitor, wortmaunin" Biochem.Biophys.Res.Comm.185. 1016-1021 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.Hashimoto,……& Y.Nonomura: "Two thrombin・activated Ca^<2+> channels in human platelets" J.Biol.Chem.267. 17078-17081 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] H.Kanoh,… Y.Nonomura & Y.Nozawa: "Enhanuing effect of wortmannia on museolinic stimalation of phospholipase D" Biochem.Biophys.Res.Comm.188. 510-515 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Nakamura;T.Sakurai;Y.Nonomura: "Determination of the uative suburit pattern of gijjand tropomyosin using antibodus specific to each subunit" J.Biochem.109. 758-762 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Y.Hasnimoto;T.Nakayama;Y.Matsuda & Y.Nonomura: "Polent and preterential in bibition of Ca^<2+>/cal modulinーdependent protein kinase II by K252a and its derivative KT5926" Biochem.Biophys.Res.Comm.181. 423-429 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] S.Nakanishi;S.Kakita;Y.Hashimoto & Y.Nonomura: "Wartmannin,a microbial product inhibitor of myosin light chiain kinase" J.Biol.Chem. 267. 2157-2163 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] K.Sobue: "Caldesmon,a novel regulatory protein in swooth muscle and nou muscle artowyosin system" I.Biol.Chem.266. 12115-12118 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Matsuura & K.Maruyama: "Isolation and characterijation of 1200 KDa peptide of αーconnertin" J.Biochem.110. 474-478 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.Eto & F.Morita: "Actin polymerijation promoted by heptapeptide,an analogue of the aitinーbinding S site on myosion head" J.Biol.Chem.(1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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