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核-細胞質間物質輸送制御の視点からの脳性差発現機構解明へのアプローチ

Research Project

Project/Area Number 19657062
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Cell biology
Research InstitutionOsaka University

Principal Investigator

米田 悦啓  Osaka University, 生命機能研究科, 教授 (80191667)

Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2008: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2007: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywords核蛋白質輸送 / importin α / importin β / 性差 / 脳機能 / 核輸送因子 / 質量分析法 / ノックアウトマウス
Research Abstract

核一細胞質間蛋白質輸送機構に関する研究は、importin βファミリー分子、importin αファミリー分子、低分子量GTPase Ranやそのサイクルに関する因子群の性状解析が精力的に進められ、輸送機構に関する基本的な分子メカニズムが理解される段階にまで研究は進展した。しかし、核一細胞質間蛋白質輸送が、個体発生、細胞分化・増殖、細胞死、ストレス応答、細胞周期といった様々な生命現象とどのように深く関連しているのかという点についてはほとんど研究が進んでいない。本研究では、マウス脳において蛋白質の核輸送機構に性差による制御が存在し、それらが脳の性差発現に重要であるのではないかという仮説の下に、1)性差に着目したマウス脳における核輸送因子発現の網羅的解析、2)発現に性差が見られる核輸送因子により運ばれている脳の性差決定(維持)候補因子の同定、3)性差の見られた核輸送因子の脳内特定部位特異的なコンディショナルノックアウトマウス、及び脳の性差決定(維持)候補因子のノックアウトマウスを用いた脳性差発現の解析を行うことを目的として研究を進めた。昨年度の研究の結果、importin αファミリーに属する分子の1つであるimportin α5(NPI-1)の発現量が、蛋白質のレベルで、雌の脳(小脳、中脳、前頭葉、海馬、嗅球など)において増加していることが明らかとなった。一方、importin βの発現量には顕著な雌雄差は見られなかった。そこで、本年度は、神経細胞においてimportin α5によって輸送されている因子群の、質量分析法による網羅的同定を試みた。その結果、計47種類の脳の性差を決定する可能性のある候補分子を同定することができた。

Report

(2 results)
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (44 results)

All 2009 2008 2007 Other

All Journal Article (17 results) (of which Peer Reviewed: 17 results) Presentation (21 results) Book (4 results) Remarks (2 results)

  • [Journal Article] Infrared laser-mediated gene induction in targeted single cells in vivo.2009

    • Author(s)
      Kamei, Y., et al.
    • Journal Title

      Nature Methods 6(in press)

      Pages: 79-81

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] mDia2 shuttles between the nucleus and the cytoplasm through the Importin-α/β- and CRM1-mediated nuclear transport mechanism.2009

    • Author(s)
      Miki, T., et al.
    • Journal Title

      J. Biol. Chem. 284(in press)

      Pages: 99-104

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adaptor Aly and co-adaptor Thoc5 function in the Tap-p15-mediated nuclear export of HSP70 mRNA.2009

    • Author(s)
      Katahira, J., et al.
    • Journal Title

      EMBO J. (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selective localization of PCBP2 to cytoplasmic processing bodies.2009

    • Author(s)
      Fujimura, K., et al.
    • Journal Title

      Biochim. Biophys. Acta - Molecular Cell Research (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synergistic nuclear import of NeuroDl and its partner transcription factor E47 via heterodimerization.2009

    • Author(s)
      Mehmood, R., et al.
    • Journal Title

      Exp. Cell Res. (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles of the TREX complex in nuclear export of mRNA.2009

    • Author(s)
      Katahira, J., Yoneda, Y.
    • Journal Title

      RNA Biol. (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of nuclear transport system in cell differentiation.2009

    • Author(s)
      Yasuhara, N., et al.
    • Journal Title

      Seminars in Cell and Developmental Biology (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation and characterization of a monoclonal antibody against NPI-1 subfamily of importin α.2008

    • Author(s)
      Tachibana, T., et al.
    • Journal Title

      Hybridoma 27

      Pages: 285-289

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Localized regulation of axonal RanGTPase controls retrograde injury signaling in peripheral nerve.2008

    • Author(s)
      Yudin, D., et al.
    • Journal Title

      Neuron 59

      Pages: 241-252

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Individual binding pockets of importin βfor FG-nuclepporins are differently regulated by RanGTP.2008

    • Author(s)
      Otsuka, S., et al.
    • Journal Title

      Proc. Natl Acad. Sci. USA 105

      Pages: 16101-16106

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of human herpesvirus 6 U69 gene product and identification of its nuclear localization signal.2008

    • Author(s)
      Isegawa, Y., et. al.
    • Journal Title

      J. Virol. 82

      Pages: 710-718

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nuclear RNA export factor 7 is localized in processing bodies and neuronal mRNA granules through interactions with shuttling hnRNPs.2008

    • Author(s)
      Katahira, J., et. al.
    • Journal Title

      Nucl. Acids Res. 36

      Pages: 616-628

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NXF2 is involved in cytoplasmic mRNA dynamics through interactions with motor proteins.2007

    • Author(s)
      Takano, K., et. al.
    • Journal Title

      Nucl. Acids Res. 35

      Pages: 2513-2521

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel nuclear import of Vpr promoted by importin α is crucial for HIV-1 replication in macrophages.2007

    • Author(s)
      Nitahara-Kasahara, Y., et. al.
    • Journal Title

      J. Virol. 81

      Pages: 5284-5293

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Arxl functions as an unorthodox nuclear export receptor for the 60Spre-ribosomal subunit.2007

    • Author(s)
      Bradatsch, B., et. al.
    • Journal Title

      Mol. Cell 27

      Pages: 767-779

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Normal brain development in importin-α5 deficient-mice.2007

    • Author(s)
      Yasuhara, N., et. al.
    • Journal Title

      Nature Cell Biol. 9

      Pages: 1339-1339

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 細胞分化を制御する核輸送因子importin α2007

    • Author(s)
      安原徳子、米田悦啓
    • Journal Title

      蛋白質核酸酵素 52

      Pages: 427-433

    • NAID

      40015447931

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] C2C12細胞の筋分化における核膜孔複合体リモデリング2009

    • Author(s)
      Asally, M., Yasuda, Y., Oka, M., Otsuka, S., Yoshimura, S. H., Yoneda, Y.
    • Organizer
      第26回染色体ワークショツプ
    • Place of Presentation
      姫路
    • Related Report
      2008 Annual Research Report
  • [Presentation] Nucleocytoplasmic transport of proteins and RNAs and its significance to cell function2008

    • Author(s)
      Yoneda, Y., Katahira, J., Sekimoto, T., Yasuhara, N., Oka, M.
    • Organizer
      第60回 日本細胞生物学会大会
    • Place of Presentation
      横浜
    • Related Report
      2008 Annual Research Report
  • [Presentation] Functional differences between two isoforms of Npap60 (Nup50) in nuclear impiort2008

    • Author(s)
      Ogawa, Y., Miyamoto, Y., Oka, M., Asally, M., Yoneda, Y.
    • Organizer
      第60回 日本細胞生物学会大会
    • Place of Presentation
      横浜
    • Related Report
      2008 Annual Research Report
  • [Presentation] Nuclear accumulation of importin a suppresses DNA replication2008

    • Author(s)
      Mizuguchi, C, Yasuda, Y., Yoneda, Y.
    • Organizer
      第60回 日本細胞生物学会大会
    • Place of Presentation
      横浜
    • Related Report
      2008 Annual Research Report
  • [Presentation] Analysis of potential roles of Nup98 FG repeat region inoncogenesis2008

    • Author(s)
      Masahiro Oka, Munehiro Asally, Yoshinari Yasuda, Yoshihiro Yoneda
    • Organizer
      第60回 日本細胞生物学会大会
    • Place of Presentation
      横浜
    • Related Report
      2008 Annual Research Report
  • [Presentation] Identification of a cis-aeting dendritic targeting element in the brain-derived neurotrophic factor mRNA.2008

    • Author(s)
      Souichi Oe, Yoshihiro Yoneda
    • Organizer
      第60回 日本細胞生物学会大会
    • Place of Presentation
      横浜
    • Related Report
      2008 Annual Research Report
  • [Presentation] Nuclear protein import and its significance to cell function2008

    • Author(s)
      Yoneda, Y.
    • Organizer
      2nd International SOX Meeting
    • Place of Presentation
      兵庫
    • Related Report
      2008 Annual Research Report
  • [Presentation] Regulation of importin alpha 1 expression2008

    • Author(s)
      Yasunao Kamikawa, NorikoYasuhara, Yoshihiro Yoneda
    • Organizer
      2nd International SOX Meeting
    • Place of Presentation
      兵庫
    • Related Report
      2008 Annual Research Report
  • [Presentation] A novel regulatory system to maintain ES cells through nuclear-cytoplasmic transport2008

    • Author(s)
      Yasuhara, N, Memood, R., Kamikawa, Y., Touma, K., Yoneda, Y.
    • Organizer
      2nd International SOX Meeting
    • Place of Presentation
      兵庫
    • Related Report
      2008 Annual Research Report
  • [Presentation] Nuclear-cytoplasmic transport regulation of transcription factors2008

    • Author(s)
      Memood, R., Yoshikawa, K. Shibazaki, N., Kaneko, A. Yasuhara, N., Kondoh, H., Yoneda, Y.
    • Organizer
      2nd International SOX Meeting
    • Place of Presentation
      兵庫
    • Related Report
      2008 Annual Research Report
  • [Presentation] Nuclear import mechanism of Nanog2008

    • Author(s)
      Gibo, R., Okada, M., Yasuhara, N., Yoneda, Y.
    • Organizer
      2nd International SOX Meeting
    • Place of Presentation
      兵庫
    • Related Report
      2008 Annual Research Report
  • [Presentation] Selective localization of PCBP2 to P-bodies - An implicationfor functional diversity among P-bodies2008

    • Author(s)
      Ken Fujimura, Jun Katahira, Fumi Kano, Yoshihiro Yoneda, Masayuki Murata
    • Organizer
      Cold Spring Harbor Laboratory Meeting on Dynamic Organization of Nuclear Function
    • Place of Presentation
      N. Y. /USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] Nuclear pore dynamics during skeletal myogenesis.2008

    • Author(s)
      Asally, M., Yasuda, Y., Oka, M., Otsuka, S., Yoshimura, S. H., Yoneda, Y.
    • Organizer
      Cold Spring Harbor Laboratory Meeting on Dynamic Organization of Nuclear Function
    • Place of Presentation
      N. Y. /USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] Nuclear import mechanism of neuroDl, E47 and their heterodimeric complex.2008

    • Author(s)
      Mehmood, R., Yasuhara, N., Oe, S., Nagai, M., Yoneda, Y
    • Organizer
      Cold Spring Harbor Laboratory Meeting on Dynamic Organization of Nuclear Function
    • Place of Presentation
      N. Y. /USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] The role of Nup98 in a Crm1-mediated nuclear export.2008

    • Author(s)
      Oka, M., Asally, M., Yasuda, Y., Yoneda, Y.
    • Organizer
      Cold Spring Harbor Laboratory Meeting on Dynamic Organization of Nuclear Function
    • Place of Presentation
      N. Y. /USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] Functional analysis of nuclear importin α accumulating in response to the stress.2008

    • Author(s)
      Yasuda, Y., Miyamoto, Y., Yoneda, Y.
    • Organizer
      Cold Spring Harbor Laboratory Meeting onDynamic Organization of Nuclear Function
    • Place of Presentation
      N. Y. /USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] Nucleo-cytoplasmic transport and the assembly of stress granules2008

    • Author(s)
      Ken Fujimura, Jun Katahira, Fumi Kano, Yoshihiro Yoneda, Masayuki Murata
    • Organizer
      Cold Spring Harbor Laboratory Meeting on Dynamic Organization of Nuclear Function
    • Place of Presentation
      N. Y. /USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] 核蛋白質輸送と生命機能2008

    • Author(s)
      米田悦啓
    • Organizer
      BMB2008 第3 1回日本分子生物学会年会第8 1回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Related Report
      2008 Annual Research Report
  • [Presentation] 精子細胞形成過程におけるimportin alphaの核内機能2008

    • Author(s)
      宮本洋一, 安田善也, 山城朋子, 永井理博, 米田悦啓, David Jans, Kate Loveland
    • Organizer
      BMB2008 第3 1回日本分子生物学会年会・第8 1回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Related Report
      2008 Annual Research Report
  • [Presentation] 核-細胞質間分子流通機構と生命機能の調節2007

    • Author(s)
      米田悦啓
    • Organizer
      第71回日本生化学会中部支部会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-05-19
    • Related Report
      2007 Annual Research Report
  • [Presentation] Importin alpha has multiple functions2007

    • Author(s)
      Yoneda, Y.
    • Organizer
      EMBO Workshop on Mechanisms of Nucleocytoplasmic Transport
    • Place of Presentation
      Italy
    • Related Report
      2007 Annual Research Report
  • [Book] 分子生物学イラストレイテッド 第3版2009

    • Author(s)
      浅利宗弘, 米田悦啓
    • Total Pages
      348
    • Publisher
      羊土社
    • Related Report
      2008 Annual Research Report
  • [Book] 標準細胞生物学2008

    • Author(s)
      片平じゅん, 米田悦啓
    • Total Pages
      358
    • Publisher
      医学書院
    • Related Report
      2008 Annual Research Report
  • [Book] Nuclear Dynamics2007

    • Author(s)
      Saiwaki, T. and Yoneda, Y.
    • Total Pages
      279
    • Publisher
      Springer-Verlag Inc.
    • Related Report
      2007 Annual Research Report
  • [Book] 細胞核の世界-ダイナミクスから病態まで2007

    • Author(s)
      米田悦啓、他
    • Total Pages
      383
    • Publisher
      共立出版
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.anat3.med.osaka-u.ac.jp/

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.anat3.med.osaka-u.ac.jp/

    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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