• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

FUNCTIONAL SIGNIFICANCE OF LIPID DROPLETS AS A NEW MEMBRANE DOMAIN

Research Project

Project/Area Number 13307002
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field General anatomy (including Histology/Embryology)
Research InstitutionNagoya University

Principal Investigator

FUJIMOTO Toyoshi  NAGOYA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学系研究科, 教授 (50115929)

Co-Investigator(Kenkyū-buntansha) 向後 寛  名古屋大学, 大学院・医学系研究科, 助手 (20282387)
Project Period (FY) 2001 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2004: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2003: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2002: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywordslipid droplets / ADRP / caveolin / Rab18 / Yeast two-hybrid / mass spectrometry / ARF1 / RNAi / 脂質エステル / 欠失ミュータント / 脂肪滴 / 膜ドメイン / ラフト / カベオリン / シグナル伝達
Research Abstract

Lipid droplets(LDs) have been regarded simply as a depot of lipids in specially differentiated cells, e.g., white adipose cells. But in fact LDs are found virtually in any cell type, but their function has been left ambiguous. In the present study, we attempted to examine the physiological function of LDs mainly in non-adipose cells, and obtained the following results.
1)Caveolins, especially caveolin-2β, was preferentially localized in the surface of LDs. The central hydrophobic portion of caveolin-2βwas necessary for the localization. Other caveolins, including caveolin-1 and caveolin-2α were also localized to LDs when the ER-to-Golgi transport was inhibited by brefeldin A.
2)The LD surface was shown to be a phospholipid monolayer containing free cholesterol. The fatty acid composition of the LD phospholipids was unique and different from that of the ER and rafts.
3)ADRP (or adipophilin), a protein specifically localized to LDs in non-adipose cells, was targeted to LDs by using different sequence cues from caveolins. Two redundant signals were found in the N and C termini of the ADRP molecule.
4)ADRP was shown to bind to ARF1,and was dissociated from LDs when cells were treated with brefeldin A or GDP-bound ARF1.
5)By proteomic analysis of purified LDs, Rab18 was identified as an LD-specific protein.
Overexpression of Rab18 eliminated ADRP from the LD surface, and induced formation of the LD-ER apposition. The same apposition was formed when the expression of ADRP was knocked down by RNA interference or when cells were treated by brefeldin A.
These results indicate that LDs do not simply store excessive lipids, but may be involved in various important functions including intracellular lipid trafficking and metabolism.

Report

(5 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (22 results)

All 2004 2002 2001 Other

All Journal Article (16 results) Publications (6 results)

  • [Journal Article] ADRP is dissociated from lipid droplets by ARF1-dependent mechanism2004

    • Author(s)
      Nakamura, N., T.Akashi, T.Taneda, H.Kogo, A.Kikuchi, T.Fujimoto
    • Journal Title

      Biochem.Biophys.Res.Commun. 322

      Pages: 957-965

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Cell type-specific occurrence of caveolin-1alpha and-1beta in the lung caused by expression of distinct mRNAs.2004

    • Author(s)
      Kogo, H., T.Aiba, T.Fujimoto
    • Journal Title

      J.Biol.Chem. 279

      Pages: 25574-25581

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Human coronavirus 229E binds to CD13 in raft and enters the cell through caveolae2004

    • Author(s)
      Nomura, R., A.Kiyota, E.Suzaki, K.Kataoka, Y.Ohe, K.Miyamoto, T.Senda, T.Fujimoto
    • Journal Title

      J.Virol. 78

      Pages: 8701-8708

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] ADRP is dissociated from lipid droplets by ARF1-dependent mechanism.2004

    • Author(s)
      Nakamura, N., T.Akashi, T.Taneda, H.Kogo, A.Kikuchi, T.Fujimoto
    • Journal Title

      Biochem.Biophys.Res.Commun. 322

      Pages: 957-965

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cell type-specific occurrence of caveolin-1 alpha and-1 beta in the lung caused by expression of distinct mRNAs.2004

    • Author(s)
      Kogo, H., T.Aiba, T.Fujimoto
    • Journal Title

      J.Biol.Chem. 279

      Pages: 25574-25581

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Human coronavirus 229E binds to CD13 in raft and enters the cell through caveolae.2004

    • Author(s)
      Nomura, R., A.Kiyota, E.Suzaki, K.Kataoka, Y.Ohe, K.Miyamoto, T.Senda, T.Fujimoto
    • Journal Title

      J.Virol. 78

      Pages: 8701-8708

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cell type-specific occurrence of caveolin-1alpha and -1beta in the lung caused by expression of distinct mRNAs.2004

    • Author(s)
      Kogo, H., T.Aiba, T.Fujimoto
    • Journal Title

      J.Biol.Chem. 279

      Pages: 25574-25581

    • Related Report
      2004 Annual Research Report
  • [Journal Article] In vitro of gut-like structures from mouse embryonic stem cells2004

    • Author(s)
      Kuwahara, M., T.Ogaeri, R.Matsuura, H.Kogo, T.Fujimoto, S.Torihashi
    • Journal Title

      Neurogastroenterol.Motil. 16

      Pages: 14-18

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Human coronavirus 229E binds to CD13 in raft and enters the cell through caveolae2004

    • Author(s)
      Nomura, R, A.Kiyota, E.Suzaki, K.Kataoka, Y.Ohe, K.Miyamoto, T.Senda, T.Fujimoto
    • Journal Title

      J.Virol. 78

      Pages: 8701-8708

    • Related Report
      2004 Annual Research Report
  • [Journal Article] New monoclonal antibody (AIC) identifies interstitial cells of Cajal in the musculature of the mouse gastrointestinal tract.2004

    • Author(s)
      Torihashi, S., K.Yokoi, H.Nagaya, K.Aoki, T.Fujimoto
    • Journal Title

      Auton Neurosci. 113

      Pages: 16-23

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Requirement for TSP-15, a tetraspanin protein, for epidermal integrity in Caenorhabditis elegans.2004

    • Author(s)
      Moribe, H., J.Yochem, H.Yamada, Y.Tabuse, T.Fujimoto, E.Mekada
    • Journal Title

      J.Cell Sci. 117

      Pages: 5209-5220

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Deformation of lipid droplets in fixed samples.2002

    • Author(s)
      Fukumoto, S., T.Fujimoto
    • Journal Title

      Histochem.Cell Biol. 118

      Pages: 423-428

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The surface of lipid droplets is a phospholipid monolayer with a unique fatty acid composition.2002

    • Author(s)
      Tauchi-Sato, K., S.Ozeki, T.Houjou, R.Taguchi, T.Fujimoto
    • Journal Title

      J.Biol.Chem. 277

      Pages: 44507-44512

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The surface of lipid droplets is a phospholipid monolayer with a unique fatty acid composition.2002

    • Author(s)
      Tauchi-Sato, K., S.Ozeki, T.Houjou, R.Taguchi, T.Fujimoto
    • Journal Title

      J.Biol.Chem 277

      Pages: 44507-44512

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Caveolin-2 is targeted to lipid droplets, a new "membrane domain" in the cell.2001

    • Author(s)
      Fujimoto, T., H.Kogo, K.Ishiguro, K.Tauchi, R.Nomura
    • Journal Title

      J.Cell Biol. 152

      Pages: 1079-1085

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Caveolin-2 is targeted to lipid droplets, a new ‘membrane domain' in the cell.2001

    • Author(s)
      Fujimoto, T., H.Kogo, K.Ishiguro, K.Tauchi, R.Nomura
    • Journal Title

      J.Cell Biol. 152

      Pages: 1079-1085

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Nakamura, N., Fujimoto, T.: "Adipose-differentiation-related protein has two independent domains for targeting to lipid droplets"Biochem.Biophys.Res.Commun.. 306. 333-338 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Aoki, T., Kogure, S., Kogo, H., Hayashi, Y., Ohno-Iwashita, Y., Fujimoto, T.: "Sequestration of cross-linked membrane molecules to caveolae in two different pathways"Acta Histochem.Cytochem.. 36. 165-171 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fukumoto, S., T.Fujimoto: "Deformation of lipid droplets in fixed samples"Histochem.Cell Biol.. 118. 423-428 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tauchi-Sato, K., S.Ozeki, T.Houjou, R.Taguchi, T.Fujimoto: "The surface of lipid droplets is a phospholipid monolayer with a unique fatty acid composition"J.Biol.Chem.. 277. 44507-44512 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujimoto, T., H.Kogo, K.Ishiguro, K.Tauchi, R.Nomura: "Caveolin-2 is targeted to lipid droplets, a new "membrane domain"in the cell"J.Cell Biol.. 152. 1079-1085 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 向後寛, 藤本豊士: "カベオリンと脂質"蛋白質・核酸・酵素. 46. 789-797 (2001)

    • Related Report
      2001 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi