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Molecular dissection of organization and dynamics of membrane lipid domains

Research Project

Project/Area Number 14370753
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionRIKEN

Principal Investigator

KOBAYASHI Toshihide  RIKEN, Sphingolipid functions lab., Head of the laboratory, スフィンゴ脂質機能研究チーム, チームリーダー (60162004)

Co-Investigator(Kenkyū-buntansha) SHOGOMORI Hidehiko  RIKEN, Sphingolipid functions lab., Researcher, スフィンゴ脂質機能研究チーム, 研究員 (80391986)
ISHITSUKA Reiko  RIKEN, Lipid biology lab., Researcher, 小林脂質生物学研究室, 研究員 (60342747)
MAKINO Asami  RIKEN, Sphingolipid functions lab., Research associate, スフィンゴ脂質機能研究チーム, リサーチアソシエイト (20373368)
MURATE Motohide  RIKEN, Sphingolipid functions lab., Researcher, スフィンゴ脂質機能研究チーム, 研究員 (30311369)
清水 善久  独立行政法人理化学研究所, スフィンゴ脂質機能研究チーム, フロンティア研究員 (80344042)
清川 悦子  独立行政法人理化学研究所, スフィンゴ脂質機能研究チーム, フロンティア研究員 (80300929)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥8,600,000 (Direct Cost: ¥8,600,000)
KeywordsSphingomyelin / Lipid raft / Cholesterol / Lipid probe / Membrane domain / Lipid-binding toxin / Endocytosis / Flip-flop / 膜結合性毒素 / 糖脂質 / MDCK細胞 / 細胞極性 / エンドソーム / 脂質ドメイン / リゾビスホスファチジン酸 / ホスファチジルエタノールアミン / 膜融合
Research Abstract

Whereas the bilayer organization of biomembranes can be reconstituted in artificial liposomes with a simple lipid composition, biological membranes contain thousands of different lipid species, whose cellular distribution is stringently controlled. This complex distribution of lipids suggests that the targeting of lipids is highly regulated and that cells require a complex lipid supramolecular organization within their membranes. Our aim is to understand the organization, assembly and function of specific lipids and lipid domains. For this purpose, we developed several lipid-specific probes and a new inhibitor of Sphingolipid biosynthesis. These tools, in conjunction with biochemical, biophysical and cell biological approaches are now starting to provide valuable information to understand lipid supramolecular organization. Application of our probes uncovered several aspects of cellular lipid organization. Major subjects performed during these three years are :
1.Characterization of sphingomyelin-specific toxin, lysenin
2.Studies on organization and dynamics of sphingomyelin
3.Characterization of sulfamisterin (AB5366), a new inhibitor of serine palmitoyltransferase
4.Studies on distribution and transport of cholesterol-rich membrane domains
5.Cellular distribution of phosphatidylethanolamine in yeast

Report

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

    (32 results)

All 2005 2004 2003 2002 Other

All Journal Article (18 results) Book (1 results) Patent(Industrial Property Rights) (2 results) Publications (11 results)

  • [Journal Article] Spatial and functional heterogeneity of sphingolipid-rich membrane domains2005

    • Author(s)
      Kiyokawa E.
    • Journal Title

      J.Biol.Chem. in press

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Spatial and functional heterogeneity of sphingolipid-rich membrane domains.2005

    • Author(s)
      Kiyokawa E, Baba T, Otsuka N, Makino A, Ohno S, Kobayashi T.
    • Journal Title

      J.Biol.Chem (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Fungal metabolite sulfamisterin suppresses sphingolipid synthesis through inhibition of serine palmitoyltrnasferase2005

    • Author(s)
      Yamaji-Hasegawa A
    • Journal Title

      Biochemistry 44

      Pages: 268-277

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Inhibition mechanism of Dlac-acetogenesis : A novel type of inhibitors of bovine heart mitochondria complex I2005

    • Author(s)
      Ichimaru N
    • Journal Title

      Biochemistry 44

      Pages: 816-825

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Human CHMP6, a myristoylated ESCORT-III protein, interacts directly with an ESCORT-II component EAP20 and regulates endosomal cargo sorting.2005

    • Author(s)
      Yorikawa C
    • Journal Title

      Biochem.J. (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A lipid-specific toxin reveals heterogeneity of sphingomyelin-containing membranes2004

    • Author(s)
      Ishitsuka R.
    • Journal Title

      Biophys.J. 86

      Pages: 296-307

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Distribution and transport of cholesterol-rich membrane domains monitored by a membrane-impermeant fluorescent polyethylene glycol-derivatized cholesterol2004

    • Author(s)
      Sato SB.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 23790-23796

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Recognition of sphingomyelin by lysenin and lysenin-related proteins2004

    • Author(s)
      Kiyokawa E.
    • Journal Title

      Biochemistry 43

      Pages: 9766-9773

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A lipid-specific toxin reveals heterogeneity of sphingomyelin-containing membranes.2004

    • Author(s)
      Ishitsuka R, Yamaji-Hasegawa A, Makino A, Hirbayashi Y, Kobayashi T.
    • Journal Title

      Biophys.J. 86

      Pages: 296-307

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Distribution and transport of cholesterol-rich membrane domains monitored by a membrane-impermeant fluorescent polyethylene glycol-derivatized cholesterol.2004

    • Author(s)
      Sato SB, Ishii K, Makino A, Iwabuchi K, Yamaji-Hasegawa A, Senoh Y, Nagaoka I, Sakuraba H, Kobayashi T.
    • Journal Title

      J.Biol.Chem 279

      Pages: 23790-23796

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Recognition of sphingomyelin by lysenin and lysenin-related proteins.2004

    • Author(s)
      Kiyokawa E, Makino A, Ishii K, Otsuka N, Yamaji-Hasegawa A, Kobayashi T.
    • Journal Title

      Biochemistry 43

      Pages: 9766-9773

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Distribution and transport of cholesterol-rich membrane domains monitored by a membrane-impermeant fluorescent polyethylene glycol-derivatized cholesterol2004

    • Author(s)
      Sato SB
    • Journal Title

      J.Biol.Chem. 279

      Pages: 23790-23796

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Recognition of sphingomyelin by lysenin and lysenin-related proteins2004

    • Author(s)
      Kiyokawa E
    • Journal Title

      Biochemistry 43

      Pages: 9766-9773

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Local exposure of phosphatidylethanolamine on the yeast plasma membranes is implicated in cell polarity2004

    • Author(s)
      Iwamoto K
    • Journal Title

      Genes Cells 9

      Pages: 891-903

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cinnamycin (Ro 09-0198) promotes cell binding and toxicity by inducing transbilayer lipid movement2003

    • Author(s)
      Makino A.
    • Journal Title

      J.Biol.Chem. 278

      Pages: 3204-3209

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Oligomerization and pore formation of a sphingomyelin-specific toxin, lysenin2003

    • Author(s)
      Yamaji-Hasegawa A.
    • Journal Title

      J.Biol.Chem. 278

      Pages: 22762-22770

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cinnamycin (Ro09-0198) promotes cell binding and toxicity by inducing transbilayer lipid movement.2003

    • Author(s)
      Makino A, Baba T, Fujimoto K, Iwamoto K, Yano Y, Terada N, Ohno S, Sato SB, Ohta A, Umeda M, Matsuzaki K, Kobayashi T.
    • Journal Title

      J.Biol.Chem 278

      Pages: 3204-3209

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Oligomerization and pore formation of a sphingomyelin-specific toxin, lysenin.2003

    • Author(s)
      Yamaji-Hasegawa A, Makino A, Baba T, Senoh Y, Kimura-Suda H, Sato B S, Terada N, Ohno S, Kiyokawa E, Umeda M, Kobayashi T.
    • Journal Title

      J.Biol.Chem 278

      Pages: 22762-22770

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Cell Biology : A Laboratory Handbook2005

    • Author(s)
      Kobayashi T
    • Publisher
      Elsevier(in press)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] コレステロール検出試薬2002

    • Inventor(s)
      小林 俊秀
    • Industrial Property Rights Holder
      理化学研究所
    • Industrial Property Number
      2002-160277
    • Filing Date
      2002-05-31
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] Sphingomyelin detecting probe2002

    • Inventor(s)
      Toshihide Kobayashi
    • Industrial Property Rights Holder
      RIKEN
    • Filing Date
      2002-05-07
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Yamaji-Hasegawa A.: "Oligomerization and pore formation of a sphingomyelin-specific toxin, lysenin"J.Biol.Chem.. 278. 22762-22770 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nagatsuka Y.: "Carbohydrate-dependent signaling from the phosphatidylglucoside-based microdomain induces granulocytic differentiation of HL60 cells"Proc.Natl.Acad.Sci.USA. 100. 7454-7459 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishitsuka R.: "Alipid-specific toxin reveals heterogeneity of sphingomyelin-containing membranes"Biophys.J.. 86. 296-307 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Laulagnier K: "Mast cell and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization"Biochem J. In press. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 石塚 玲子: "ラフトの概念"生体の科学. 54. 260-265 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kobayashi T.: "Cell Biology : A Laboratory Handbook"Elsevier Inc. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kobayashi, T.: "Separation and characterization of late endosomal membrane domains"J.Biol.Chem.. 277. 32157-32146 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kato, U.: "A novel membrane protein, Ros3p, is required for phospholipid translocation across the plasma membrane in Saccharomyces cerevisiae"J.Biol.Chem.. 277. 37855-37862 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takahashi, H.: "Long-term systemic therapy of Fabry disease in a knockout mouse by adeno-associated virus-mideated muscle-directed gene transfer"Proc.Natl.Acad.Sci.USA. 99. 13777-13782 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Makino, A.: "Cinnamycin (Ro09-0198) promotes cell binding and toxicity by inducing transb ilayer lipid movement"J.Biol.Chem.. 278. 3204-3209 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 山路-長谷川 顕子: "スフィンゴミエリンを認職するタンパク質群"蛋白質核酸酵素. 47. 519-525 (2002)

    • Related Report
      2002 Annual Research Report

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

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