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細胞極性の形成・維持におけるメンブレントラフィックの役割

Research Project

Project/Area Number 15079202
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionGunma University

Principal Investigator

原田 彰宏  Gunma University, 生体調節研究所, 教授 (40251441)

Co-Investigator(Kenkyū-buntansha) 佐藤 健  群馬大学, 生体調節研究所, 准教授 (30311343)
佐藤 隆史  群馬大学, 生体調節研究所, 助教 (70344934)
Project Period (FY) 2003 – 2008
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥105,000,000 (Direct Cost: ¥105,000,000)
Fiscal Year 2007: ¥18,900,000 (Direct Cost: ¥18,900,000)
Fiscal Year 2006: ¥18,900,000 (Direct Cost: ¥18,900,000)
Fiscal Year 2005: ¥19,600,000 (Direct Cost: ¥19,600,000)
Fiscal Year 2004: ¥23,800,000 (Direct Cost: ¥23,800,000)
Fiscal Year 2003: ¥23,800,000 (Direct Cost: ¥23,800,000)
Keywords細胞極性 / 極性輸送 / ノックアウトマウス / 線虫 / RNAiライブラリー / 遺伝子 / 細胞・組織 / 神経科学 / 蛋白質 / 発生・分化 / TGN / rab / SNARE / Cre / loxP
Research Abstract

細胞の極性の形成、維持には、合成された分泌蛋白や膜蛋白がTGN等で輸送小胞に分配、濃縮された後、apicalやbasolateralに運ばれる必要がある。この方向性のある輸送を極性輸送と呼ぶ。極性輸送には、低分子量GTP結合蛋白質、SNARE蛋白等が重要と考えられている。しかしこれらの蛋白の組織や個体における役割が明らかでないため、ごれらの蛋白を個体レベルで欠損させて検討する必要がある。そこで本研究では、
(1) gene targeting法でこれらの欠損マウスを作製し、細胞極性の形成、維持への影響や、発生・器官形成、組織の機能への影響について解析した。これらの遺伝子欠損マウスは発生異常により胎生致死になる可能性が高いため、組織、時期特異的gene targetingを行った。既にrab8a, b, syntaxin3, VAMP7, MAL2, SNAP23, Annexin13, FAPP1,2, PKD1,2を欠損したマウスの作製が終了し、解析まで進んでいる。その中で最初にRab8a欠損マウスをNature誌に報告した。更に他の既知の遺伝子についても欠損マウスを作製中である。
(2)線虫(C. elegans)を用いて細胞内極性輸送に関与する新規分子を同定、解析するため、腸細胞における極性輸送に異常を来した線虫の変異体のスクリーニングを行い、様々な新規遺伝子の同定に成功した。現在、線虫で同定した新規の極性輸送関連分子をマウスでknockoutしてこれらの分子の機能を解明し、細胞極性の形成・維持機構の包括的な解明を行っている。

Report

(5 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (26 results)

All 2009 2008 2006 2005 2004 Other

All Journal Article (14 results) (of which Peer Reviewed: 7 results) Presentation (5 results) Book (1 results) Remarks (1 results) Publications (5 results)

  • [Journal Article] Investigation of the role of oligopeptide transporter PEPT1 and sodium/glucose cotaransporter SGLT1 in intestinal obsorption of their substrates using small GTP-binding protein Rab8-null mice.2009

    • Author(s)
      Yukio Kato
    • Journal Title

      Drug metabolism and disposition 37

      Pages: 602-607

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SAP-1 is a microvillus-specific protein tyrosine phosphatase that modulates intestinal tumorigenesis.2009

    • Author(s)
      Hisanobu Sadakata
    • Journal Title

      Genes to cells 14

      Pages: 295-308

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of proton-sensing TDAG8 in extracellular acidification-induced inhibition of proinflammatory cytokine production in peritoneal macrophages.2009

    • Author(s)
      Chihiro Mogi
    • Journal Title

      The journal of immunology 182

      Pages: 3243-3251

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] p31 deficiency influences endoplasmic reticulum tubular morphology and cell survival.2009

    • Author(s)
      Takefumi Uemura
    • Journal Title

      Molecular and cellular biology 29

      Pages: 1869-1881

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuron-specific recombination by Cre recombinase inserted into the murine tau locus.2008

    • Author(s)
      Kazuhiro Muramatsu
    • Journal Title

      Biochemical and biophysical research communications 370

      Pages: 419-423

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuron-specific and inducible recombination by Cre recombinase in the mouse.2008

    • Author(s)
      Yukiko Hashimoto
    • Journal Title

      Neuroreport 19

      Pages: 621-624

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rab11 is required for synchronous secretion of chondroitin proteoglycans after fertilization in Caenorhabditis elegans.2008

    • Author(s)
      Miyuki Sato
    • Journal Title

      Journal of cell science 121

      Pages: 3177-3186

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathogenesis and treatment of autosomal-dominant nephrogenic diabetes insipidus caused by an aquaporin 2 mutation2006

    • Author(s)
      Eisei Sohara
    • Journal Title

      Proceedings of the National Academy of Sciences of the United States of America 103・38

      Pages: 14217-14222

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Dynamic regulation of caveolin-1 trafficking in the germ line and embryo of Caenorhabditis elegans2006

    • Author(s)
      Ken Sato
    • Journal Title

      Molecular Biology of the Cell 17・7

      Pages: 3085-3094

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Caenorhabditis elegans RME-6 is a novel regulator of RAB-5 at the clathrin-coated pit.2005

    • Author(s)
      Miyuki Sato
    • Journal Title

      Nature Cell Biology 7・6

      Pages: 559-569

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Reduced expression of kinase-associated phosphatase in cortical dendrites of MAP2-deficient mice.2005

    • Author(s)
      Nobuhisa Iriuchijima
    • Journal Title

      Biochemical and Biophysical Research Communications 338・2

      Pages: 1216-1221

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Defective function of GABA-containing synaptic vesicles in mice lacking the AP-3B clathrin adaptor2004

    • Author(s)
      Fubito Nakatsu
    • Journal Title

      The Journal of Cell Biology 167・2

      Pages: 293-302

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Gem GTPase and tau : morphological changes induced by gem GTPase in cho cells are antagonized by tau2004

    • Author(s)
      Fumitaka Oyama
    • Journal Title

      The Journal of Biological Chemistry 279・26

      Pages: 27272-27277

    • Related Report
      2004 Annual Research Report
  • [Journal Article] TDAG8 is a proton-sensing and psychosine-sensitive G-protein-coupled receptor2004

    • Author(s)
      Ju-Qiang Wang
    • Journal Title

      The Journal of Biological Chemistry 279・44

      Pages: 45626-45633

    • Related Report
      2004 Annual Research Report
  • [Presentation] 極性輸送関連分子欠損マウスを用いた細胞極性形成、維持メカニズムの解明2009

    • Author(s)
      原田彰宏
    • Organizer
      第114回日本解剖学会総会
    • Place of Presentation
      岡山
    • Year and Date
      2009-03-30
    • Related Report
      2007 Annual Research Report
  • [Presentation] 細胞極性及び脂質輸送関連タンパクFAPP1,2のノックアウトマウスの解析2009

    • Author(s)
      植村武文
    • Organizer
      第114回日本解剖学会総会
    • Place of Presentation
      岡山
    • Year and Date
      2009-03-28
    • Related Report
      2007 Annual Research Report
  • [Presentation] 細胞極性及び脂質輸送関連タンパクFAPP1,2遺伝子ノックアウトマウスの作製と解析2008

    • Author(s)
      原田彰宏
    • Organizer
      第31回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-09
    • Related Report
      2007 Annual Research Report
  • [Presentation] 小腸上皮細胞の細胞極性及び機能におけるRab8の役割2008

    • Author(s)
      原田彰宏
    • Organizer
      第60回日本細胞生物学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2008-06-30
    • Related Report
      2007 Annual Research Report
  • [Presentation] 小胞体局在のt-SNARE, p31のノックアウトマウスの作製と解析について2008

    • Author(s)
      植村武文
    • Organizer
      第60回日本細胞生物学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2008-06-29
    • Related Report
      2007 Annual Research Report
  • [Book] 蛋白質核酸酵素 増刊『メンブレントラフィックの奔流』2008

    • Author(s)
      原田彰宏
    • Publisher
      共立出版
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://traffic.dept.med.gunma-u.ac.jp/

    • Related Report
      2007 Annual Research Report
  • [Publications] Kensuke Hayashi: "Inhibitory neurons from fetal rat cerebral cortex exert delayed axon formation and active migration in vitro."Journal of Cell Science. 116・21. 4419-4428 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takashi Sato: "Brain masculinization requires androgen receptor function"Proc.Natl.Acad.Sci.USA. 101・6. 1673-1678 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirotaka Kawano: "Suppressive function of androgen receptor in bone resorption"Proc.Natl.Acad.Sci.USA. 100・16. 9416-9421 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yuko Nakamichi: "Chondromodulin I is a bone remodeling factor"Molecular and Cellular Biology. 23・2. 636-644 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takashi Sato: "Late onset of obesity in male androgen receptor-deficient mice"Biochem Biophys Res Commun.. 300・1. 167-171 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2018-03-28  

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