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Metabolic regulation and intracellular transport of phospholipids in mammalian cells

Research Project

Project/Area Number 14380341
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionKYUSHU UNIVERSITY (2003-2005)
National Institute of Infectious Diseases (2002)

Principal Investigator

KUGE Osamu  KYUSHU UNIVERSITY, Faculty of Sciences, Professor, 大学院・理学研究院, 教授 (30177977)

Project Period (FY) 2002 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2005: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥3,900,000 (Direct Cost: ¥3,900,000)
Keywordsphospholipids / phosphatidylserine / biosynthesis / metabolic regulation / intracellular transport / 脂質 / 生合性 / 変異株 / 生体膜 / ホスファチジルエタノールア / CHO細胞 / 生合成酵素
Research Abstract

1)Study on the metabolic regulation of phospholipids
Phosphatidylserine (PS) in mammalian cells is synthesized through the action of ER membrane enzymes, PS synthase (PSS) 1 and 2, activities of which are post-translationally regulated by PS-mediated inhibition.
(1)We purified Chinese hamster PSS 2 to near homogeneity. The kinetic analysis of the purified enzyme suggested that PSS 1 was inhibited by the binding of PS to a putative regulatory site of the enzyme.
(2)To identify amino acid residues crucial for activity and/or regulation of PSS 1, we systematically introduced alanine replacement mutations into a Chinese hamster PSS 1 cDNA clone. On analysis of CHO cells transfected with each of the mutant clones, we identified 8 and 6 amino acid residues, respectively, as those crucial for the enzyme activity and regulation.
(3)Membrane topology analysis of PSS 1 suggested that PSS 1 contained ten transmembrane segments, which placed the N and C termini in the cytosol. Furthermore, it was suggested that all of the eight amino acid residues important for the activity were placed from the center to luminal side of ER membrane, and that all of six amino acid residues important for enzyme regulation were exposed to the cytosol.
2)Study on the intracellular transport of phospholipids
(1)We identified a novel mammalian protein, MSBP1 involved in the PS transport from ER to mitochondria.
(2)We isolated 〜40 candidates for yeast mutants that were defective in the intracellular transport of PS.

Report

(5 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (18 results)

All 2006 2005 2004 2003 Other

All Journal Article (15 results) Publications (3 results)

  • [Journal Article] 哺乳動物細胞におけるリン脂質の生合成制御2006

    • Author(s)
      久下 理
    • Journal Title

      実験医学 24

      Pages: 924-928

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Phosphatidylserine is involved in gene expression from Sindbis virus subgenomic prometer2006

    • Author(s)
      Kyoko Saito
    • Journal Title

      Biochem.Biophys.Res.Commun. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Biosynthetic regulation of phospholipids in mammalian cells2006

    • Author(s)
      Kuge, O
    • Journal Title

      Jiken-igaku 24

      Pages: 924-928

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Requirement of an IkappaB-beta COOH terminal region protein for acidic-adaptation in CHO cells2006

    • Author(s)
      Qizong Lao
    • Journal Title

      Journal of Cellular Physiology 207

      Pages: 238-243

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 動物細胞のホスファチジルセリン合成酵素2005

    • Author(s)
      久下 理
    • Journal Title

      脂質生化学研究 Circular 2005

      Pages: 25-29

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Phosphatidylserine synthase of mammalian cells2005

    • Author(s)
      Kuge, O.
    • Journal Title

      Circular of the Japanese conference on the biochemistry of lipids

      Pages: 25-29

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] An IkappaB-beta COOH terminal region protein is essential for the proliferation of CHO cells under acidic stress2005

    • Author(s)
      Qizong Lao
    • Journal Title

      Journal of Cellular Physiology 203

      Pages: 186-192

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Functional analysis of Chinese hamster phosphatidylserine synthase l through systematic alanine mutagenesis2004

    • Author(s)
      Tomoko Ohsawa
    • Journal Title

      Biochem.J. 381

      Pages: 853-859

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Functional analysis of Chinese hamster phosphatidylserine synthase 1 through systematic alanine mutagenesis2004

    • Author(s)
      Ohsawa, T., Nishijima, M., Kuge, O.
    • Journal Title

      Biochem.J. 381

      Pages: 853-859

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Functional analysis of Chinese hamster phosphatidylserine synthase 1 through synstematic alanine mutagenesis2004

    • Author(s)
      Ohsawa, T., Nishijima, M., Kuge, O.
    • Journal Title

      Biochem.J. 381

      Pages: 853-859

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Biosynthetic regulation and intracellular transport of phosphatidylserine in mammalian cells2003

    • Author(s)
      Osamu Kuge
    • Journal Title

      J.Biochem. 133

      Pages: 397-403

    • NAID

      50000824883

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Purification and characterization of Chinese hamster phosphatidylserine synthase 22003

    • Author(s)
      Osamu Kuge
    • Journal Title

      J.Biol.Chem. 278

      Pages: 42692-42698

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Biosynthetic regulation and intracellular transport of phosphatidylserine in mammalian cells2003

    • Author(s)
      Kuge, O., Nishijima, M.
    • Journal Title

      J.Biochem. 133

      Pages: 397-403

    • NAID

      50000824883

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Purification and characterization of Chinese hamster phosphatidylserine synthase 22003

    • Author(s)
      Kuge, O., Hasegawa, K., Ohsawa, T., Saito, K., Nishijima, M.
    • Journal Title

      J.Biol.Chem. 278

      Pages: 42692-42698

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Phosphatidylserine is involved in gene expression from Sindbis virus subgenomic promoter

    • Author(s)
      Saito, K., Nishijima, M., Kuge, O.
    • Journal Title

      Biochem.Biophys.Res.Commun. (In press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Publications] Kuge, O., Hasegawa, K., Ohsawa, T., Saito, K., Nishijima, M.: "Purification and Characterization of Chinese Hamster Phosphatidylserine Syntase 2"J.Biol.Chem.. 278・43. 42692-42698 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kuge, O., Nishijima, M.: "Biosynthetic Regulation and Intracellular Transport of Phosphtidylserine in Mammalian Cells"J.Biochem.. 133・4. 397-403 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Osamu Kuge, Masahiro Nishijima: "Biosynthetic regulation and intracellular transport of phosphatidylserine in mammalian cells"J. Biochemistry. (In press). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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