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パルミトイルサイクルによるG蛋白質の動態制御機構

Research Project

Project/Area Number 20054022
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionNational Institute for Physiological Sciences

Principal Investigator

深田 正紀  National Institute for Physiological Sciences, 細胞器官研究系, 教授 (00335027)

Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2009: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2008: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywords脂質修飾 / パルミトイル化 / 酵素 / G蛋白質 / 生化学 / GFPイメージング / 細胞生物学 / 翻訳後修飾 / 全反射顕微鏡
Research Abstract

GTP結合蛋白質の多くはパルミトイル化脂質修飾を受けることにより、特定の膜マイクロドメインに局在し分子スイッチとして機能する。例えば三量体G蛋白質Gαや低分子量G蛋白質H-Rasなどがパルミトイル化修飾を受ける。しかし、パルミトイル化酵素が不明であったためパルミトイル化修飾によるG蛋白質の動態制御機構に関しては不明であった。昨年度までに、私どもは23種類のパルミトイル化酵素の中から、Gαをパルミトイル化する酵素としてDHHC3/7を同定した。今年度は1)DHHC3/7によるG蛋白質動態制御機構の解明、および2)パルミトイル化酵素ファミリーの多様な活性制御機構の解明を目指した。今年度の研究実績は以下のとおりである。
GFP融合型Gαqを用いたFRAP/FLIP法、および光変換蛍光蛋白質Dendra2との融合型Gαqを用いたphotoconversion法を用いて細胞内Gαqの動態を解析した。その結果、細胞膜に存在するパルミトイル化Gαqは脱パルミトイル化を受けた後速やかにDHHC3/7が存在するゴルジ装置に移行し、DHHC3/7により再パルミトイル化され再び細胞膜に輸送されることを見出した(堤らMol. Cell. Biol. 2009)。また、神経細胞のような極性化した細胞においては、細胞体のゴルジ装置においてDHHC3がGαqやPSD-95など多くの基質を恒常的にパルミトイル化するが、樹状突起上のポストシナプスにおいては別のサブファミリーに属するDHHC2が、神経活動感受的にPSD-95をパルミトイル化することが分かった(則竹らJ. Cell BioL. 2009)。これらの成果は世界的にも高く評価され、総説(深田らNature Rev. Neuroscience, 2010)にまとめられた。このように今年度の研究計画は達成できたと考えている。

Report

(2 results)
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (39 results)

All 2010 2009 2008 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (20 results) Book (3 results) Remarks (2 results)

  • [Journal Article] Disruption of LGI1-linked synaptic complex causes abnormal synaptic transmission and epilepsy2010

    • Author(s)
      Fukata Y et al
    • Journal Title

      Proc Natl Acad Sci USA (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protein palmitoylation in neuronal development and synaptic plasticity2010

    • Author(s)
      Fukata Y et al
    • Journal Title

      Nat Rev Neurosci (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mobile DHHC palmitoylating enzyme mediates activity-sensitive synaptic targeting of PSD-952009

    • Author(s)
      Noritake J et al
    • Journal Title

      J Cell Biol 186

      Pages: 147-160

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential activity-dependent secretion of brain-derived neurotrophic factor from axon and dendrite2009

    • Author(s)
      Matsuda N et al
    • Journal Title

      J Neurosci 29

      Pages: 14185-14198

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Palmitoylation Regulates Epidermal Homeostasis and Hair Follicle Differentiation2009

    • Author(s)
      Mill P et al
    • Journal Title

      PLoS Genetics 11

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ndel1 palmitoylation : a new mean to regulate cytoplasmic dynein activity2009

    • Author(s)
      Shmueli A et al
    • Journal Title

      EMBO J 29

      Pages: 107-119

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dynamic protein palmitoylation in cellular signaling2009

    • Author(s)
      Iwanaga T et al
    • Journal Title

      Prog Lipid Res 48

      Pages: 117-127

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Hydrophobic cysteine-rich domain of SNAP25 couples with dow nstream residues to mediated membrane interactions and recognitions by DHHC palmitovl transferases2009

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

      Mol. Biol. Cell 20

      Pages: 1845-1854

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Alzheimer disease Abeta production in the absence of S-palmitoylation-dependent targeting of BACE1 to lipid rafts2009

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

      J. Biol. Chem. 284

      Pages: 3793-3803

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of G-protein alpha subunit palmitoylating enzyme2009

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

      Mol. Cell. Biol. 29

      Pages: 435-447

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dynamic protein palmitoylation in cellular signaling2009

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

      Prog Lipid Res. (In press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fibroblast Growth Factor-Regulated Palmitgylation of NCAM Determines Neuronal Morphogenesis2008

    • Author(s)
      Ponimaskin, E., et.al.
    • Journal Title

      J. Neurosci. 28

      Pages: 88897-88907

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Discovery of protein-palmitoylating enzymes2008

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

      Pflugers Arch-Eur. J. Physiol. 456

      Pages: 1199-1206

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DHHC proteins regulate stable membrane binding of the molecular ch aperone cysteine-string protein2008

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

      J. Biol. Chem. 283

      Pages: 25014-25026

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Characterization of the novel large palmitoyl acyltransferase family "Systematic identification of DHHC-PAT interacting proteins"2009

    • Author(s)
      奥慎一郎, ら
    • Organizer
      第32回日本分子生物学会大会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2009-12-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] Activity-sensitive synaptic palmitoylation of PSD-95 mediates AMPA receptor homeostasis2009

    • Author(s)
      深田正紀
    • Organizer
      Japan-Taiwan Joint Symposium on Cell Signaling and Gene Regulation
    • Place of Presentation
      神戸国際会議場(神戸)
    • Year and Date
      2009-11-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] In vivo function of epilepsy-related ligand LGI12009

    • Author(s)
      深田優子, ら
    • Organizer
      36th International Congress of Physiological Sciences
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2009-07-30
    • Related Report
      2009 Annual Research Report
  • [Presentation] Gα palmitoylating enzymes2009

    • Author(s)
      堤良平, ら
    • Organizer
      36th International Congress of Physiological Sciences
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2009-07-30
    • Related Report
      2009 Annual Research Report
  • [Presentation] A Recombinant antibody to track endogenous palmitoylated PSD-952009

    • Author(s)
      深田正紀, ら
    • Organizer
      36th International Congress of Physiological Sciences
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2009-07-28
    • Related Report
      2009 Annual Research Report
  • [Presentation] Activity-sensitive synaptic palmitoylation of PSD-95 is involved in AMPA receptor homeostasis2009

    • Author(s)
      則竹淳, ら
    • Organizer
      36th International Congress of Physiological Sciences
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2009-07-27
    • Related Report
      2009 Annual Research Report
  • [Presentation] パルイトイル化酵素ファミリーによるシナプス機能制御2009

    • Author(s)
      深田正紀
    • Organizer
      第52回日本神経化学会大会
    • Place of Presentation
      伊香保温泉ホテル天坊(渋川)
    • Year and Date
      2009-06-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] BDNFの神経活動依存的遊離の可視化2009

    • Author(s)
      松田尚人, ら
    • Organizer
      第52回日本神経化学会大会
    • Place of Presentation
      伊香保温泉ホテル天坊(渋川)
    • Year and Date
      2009-06-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] Synaptic activity regulates PSD-95 palmitoylating enzymes2009

    • Author(s)
      深田正紀, ら
    • Organizer
      The 9th Human Frontier Science Program Awardees Meeting
    • Place of Presentation
      学術総合センター(東京)
    • Year and Date
      2009-06-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] 神経活動依存的なPSD-95パルミトイル化によるAMPA型グルタミン酸受容体の恒常性の制御2009

    • Author(s)
      則竹淳, ら
    • Organizer
      第61回日本細胞生物学会大会
    • Place of Presentation
      名古屋国際会議場(名古屋)
    • Year and Date
      2009-06-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] DHHCパルミトイル化酵素によるGαの動態制御2009

    • Author(s)
      堤良平, ら
    • Organizer
      第61回日本細胞生物学会大会
    • Place of Presentation
      名古屋国際会議場(名古屋)
    • Year and Date
      2009-06-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] Synaptic palmitoylation of PSD-95 mediates AMPA receptor homeostasis2009

    • Author(s)
      深田正紀, ら
    • Organizer
      11th International Neurochemistry Winter Conference
    • Place of Presentation
      Solden, Austria
    • Year and Date
      2009-04-03
    • Related Report
      2009 Annual Research Report 2008 Annual Research Report
  • [Presentation] In vivo function of epilepsy-related ligand LGI12009

    • Author(s)
      深田優子, ら
    • Organizer
      11th International Neurochemistry Winter Conference
    • Place of Presentation
      Solders, Austria
    • Year and Date
      2009-04-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] In vivo function of epilepsy-related ligand LGI12009

    • Author(s)
      深田優子ら
    • Organizer
      11th International Neurochemistry Winter Conference
    • Place of Presentation
      Solden, Austria
    • Year and Date
      2009-03-31
    • Related Report
      2008 Annual Research Report
  • [Presentation] Physiological role of epilepsy-related ligand LGI1 in synaptic function2008

    • Author(s)
      深田優子ら
    • Organizer
      The 48th American Society for Cell Biology Annual Meeting
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2008-12-16
    • Related Report
      2008 Annual Research Report
  • [Presentation] Synaptic palmitoylation of PSD-95 mediates AMPA receptor homeostasis2008

    • Author(s)
      深田正紀ら
    • Organizer
      The 48th American Society for Cell Biology Annual Meeting
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2008-12-14
    • Related Report
      2008 Annual Research Report
  • [Presentation] シナプス伝達修飾分子LGIファミリーの性状解析2008

    • Author(s)
      岩永剛ら
    • Organizer
      第31回日本分子生物学会、第81回日本生化学会大会合同大会BMB2008
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-12
    • Related Report
      2008 Annual Research Report
  • [Presentation] Gαパルミトイル化酵素の同定と性状解析2008

    • Author(s)
      堤良平ら
    • Organizer
      第31回日本分子生物学会、第81回日本生化学会大会合同大会BMB2008
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] Activity-Dependent Regulation of the PSD-95 Palmitoylating Enzyme2008

    • Author(s)
      則竹淳ら
    • Organizer
      第31回日本神経科学大会
    • Place of Presentation
      横浜
    • Year and Date
      2008-07-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] Synaptic activity regulates PSD-95 palmitoylating enzymes2008

    • Author(s)
      深田正紀ら
    • Organizer
      The 8th Human Frontier Science Program Awardees Meeting
    • Place of Presentation
      Berlin, Germany
    • Year and Date
      2008-07-08
    • Related Report
      2008 Annual Research Report
  • [Book] 秀潤社 細胞工学2010

    • Author(s)
      岩永剛, ら
    • Publisher
      LGI1が仲介するタンパク質複合体の破綻はシナプス伝達異常とてんかんを引き起こす(In press)
    • Related Report
      2009 Annual Research Report
  • [Book] 生化学2008

    • Author(s)
      堤良平ら
    • Publisher
      日本生化学学会
    • Related Report
      2008 Annual Research Report
  • [Book] AMPA型グルタミン酸受容体の動態制御機構2008

    • Author(s)
      深田優子ら
    • Publisher
      日本神経薬理学会雑誌
    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.nips.ac.jp/fukata/

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.nips.acjp/fukata/

    • Related Report
      2008 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2018-03-28  

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