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2011 Fiscal Year Annual Research Report

カーゴ分子によるキネシン-1モーター活性制御機構の解明

Research Project

Project/Area Number 22659011
Research InstitutionHokkaido University

Principal Investigator

鈴木 利治  北海道大学, 大学院・薬学研究院, 教授 (80179233)

Keywordsキネシン / 膜小胞輸送 / カーゴ / Alcadein / 微小管
Research Abstract

キネシン-1はKIFファミリーの中で最初にイカの巨大軸索で見いだされた順行性輸送をになうモーター分子であり、2つのキネシン重鎖(KHC)と2つのキネシン軽鎖(KLC)からなるヘテロ4量体を形成している。モータードメインを持つKHCは微小管に結合しKLCはカーゴおよびカーゴ受容体に結合する。生物物理学的な解析から、キネシン-1が微小管上を移動する仕組みは解析が進んでいるが、細胞内でどのように活性化されカーゴを選択するのかは未解明の部分が多い。KHCとKLCは不活性状態で結合しており、活性化の分子機構も未解明である。AlcadeinはKLCに高親和性結合する事により、キネシン-1モーターを活性化するカーゴ受容体である(EMBO J.[2007]26,1475-1486)。本研究では、Alcadeinによりkinesin-1モーター活性化の仕組みの解明に取り組んだ。Alcadeinだけでkinesin-1を活性化出来るかを、キネシン-1の微小管結合能を測定する事で検討した。予備的な解析として、微小管結合能を持つKHCにKLCを加えると不活性化が生じる事を確認後、AlcadeinのKLC結合領域を含む細胞質ドメインを加え活性化を誘導出来るかどうか検討した。その結果、Alcadein細胞質ドメインの極めて短い配列がキネシン-1モーターを活性化出来ることを実証し、論文として発表した(Kawano,T.,(4名略)and Suzuki,T.(2012)A small peptide sequence is sufficient for initiating kinesin-1 activation through part of TPR region of KLC1.Traffic13,834-848.)。

  • Research Products

    (29 results)

All 2012 2011 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (18 results) Book (1 results) Remarks (1 results)

  • [Journal Article] A small peptide sequence is sufficient for initiating kinesin-1 activation through part of TPR region of KLC12012

    • Author(s)
      Kawano, T., Araseki, M., Araki, Y., Kinjo, M., Yamamoto, T. and Suzuki, T.
    • Journal Title

      Traffic

      Volume: 13 Pages: 834-848

    • Peer Reviewed
  • [Journal Article] FE65 as a link between VLDLR and APP to regulate their trafficking and processing2012

    • Author(s)
      Dumanis, S., 4名略, Suzuki, T., 6名略
    • Journal Title

      Molecular Neurodegeneration

      Volume: 7

    • DOI

      DOI:10.1186/1750-1326-7-9

    • Peer Reviewed
  • [Journal Article] Suppression of Alzheimer's disease-related phenotype by expression of heat shock protein 70 in mice2011

    • Author(s)
      Hoshino, T., 7名略, Suzuki, T., Mizushima, T.
    • Journal Title

      Journal of Neuroscience

      Volume: 31 Pages: 5225-5234

    • DOI

      DOI:10.1523/JNEUROSCI.5478-10.2011

    • Peer Reviewed
  • [Journal Article] Alternative γ-secretase processing of γ-secretase substrates in common forms of mild cognitive impairment and Alzheimer disease : Evidence for γ-secretase dysfunction2011

    • Author(s)
      Hata,S., Fujishige, S., 21名略, Suzuki, T.
    • Journal Title

      Annals of Neurology

      Volume: 69 Pages: 1026-1031

    • DOI

      DOI:10.1002/ana.22343

    • Peer Reviewed
  • [Journal Article] Cystein-rich intestinal protein 2 (CRIP2) acts as a repressor of NFkB-mediated pro-angiogenic cytokins transcription to suppress tumorigenesis and angiogenesis2011

    • Author(s)
      Cheung, K.L., 7名略, Suzuki, T., 4名略
    • Journal Title

      Proceeding of National Academy of Science USA

      Volume: 108 Pages: 8390-8395

    • DOI

      DOI:10.1073/pnas.1101747108

    • Peer Reviewed
  • [Journal Article] Intracellular trafficking of amyloid β-protein precursor (APP) regulated by novel function of X11-like2011

    • Author(s)
      Saito, Y., Akiyama, M., 6名略, Suzuki, T.
    • Journal Title

      Public Library of Science One

      Volume: 6

    • DOI

      DOI:10.1371/journal.pone.0022108

    • Peer Reviewed
  • [Journal Article] Effects of heparin and enoxaparin on APP processing and Aβ production in primary cortical neurons from Tg2576 mouse2011

    • Author(s)
      Cui, H., 2名略., Suzuki, T., 4名略
    • Journal Title

      Public Library of Science One

      Volume: 6

    • DOI

      DOI:10.1371/journal.pone.0023007

    • Peer Reviewed
  • [Journal Article] Coordinate increase of γ-secretase reaction products in the plasma of some female Japanese sporadic Alzheimer's disease patients : quantitative analysis with a new ELISA system2011

    • Author(s)
      Konnno, T., Hata, S., 9名略., Suzuki, T.
    • Journal Title

      Molecular Neurodegeneration

      Volume: 6

    • DOI

      DOI:10.1186/1750-1326-6-76

    • Peer Reviewed
  • [Journal Article] Improvement of cognitive function in Alzheimer's disease model mice by genetic and pharmacological inhibition of the EP4 receptor2011

    • Author(s)
      Hoshino, T., 6名略., Suzuki, T., Mizushima, T.
    • Journal Title

      Journal of Neurochemistry

      Volume: 120 Pages: 795-805

    • DOI

      DOI:10.1111/j.1471-4159.2011.07567.x

    • Peer Reviewed
  • [Presentation] Intracellular Trafficking of the Amyloid β-Protein Precursor Regulated by PDZ domains of X11-Like2011

    • Author(s)
      Saito, Y, Suzuki, T.
    • Organizer
      51th The American society for cell biology annual meeting
    • Place of Presentation
      Colorado Convention Center (USA)
    • Year and Date
      20111203-20111207
  • [Presentation] Molecular mechanism of kinesin-1 activation by Alcadeinα2011

    • Author(s)
      Araseki, M., 4名略., Suzuki, T.
    • Organizer
      51th The American society for cell biology annual meeting
    • Place of Presentation
      Colorado Convention Center (USA)
    • Year and Date
      20111203-20111207
  • [Presentation] Altered processing of gamma-secretase substrates and clearance of peptide products (Abeta and p3-Alc) as a pathogenesis of sporadic Alzheimer's disease. in "Invited Symposium 2-The pathological mechanisms underlying Alzheimer's disease"2011

    • Author(s)
      Suzuki, T., Hata, S.
    • Organizer
      Gerontology & Geriatrics 2011
    • Place of Presentation
      Melbourne Convention and Exhibition Center (Australia)(招待講演)
    • Year and Date
      20111023-20111027
  • [Presentation] Alcadeinのγセクレターゼによる膜内切断機構の解明2011

    • Author(s)
      Piao Yi(朴懿)、羽田沙緒里、鈴木利治
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      20110921-20110924
  • [Presentation] リン酸化によるAPPの膜マイクロドメインへの移行制御機構の解析2011

    • Author(s)
      松島隆英、鈴木利治
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      20110921-20110924
  • [Presentation] アポリポタンパク質EによるAlcadein代謝への影響2011

    • Author(s)
      木村彩乃、羽田沙緒里、鈴木利治
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      20110921-20110924
  • [Presentation] JIP-KLCl結合によるAPP輸送の効率化2011

    • Author(s)
      千葉杏子、野澤啓輔、荒関雅彦、齋藤有紀、金城政孝、鈴木利治
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      20110921-20110924
  • [Presentation] アルツハイマー病の新たな生化学的マーカー、p3-Alcの早期診断マーカーとしての可能性の検証2011

    • Author(s)
      羽田沙緒里、浦上克哉、谷口美也子、池内健、鈴木利治
    • Organizer
      第1回日本認知症予防学会学術集会
    • Place of Presentation
      米子コンベンションセンター(鳥取)
    • Year and Date
      20110909-20110911
  • [Presentation] アルツハイマー病におけるγセクレターゼの機能変化を反映するAlcadein膜内の切断機構の解析2011

    • Author(s)
      朴懿、羽田沙緒里、鈴木利治
    • Organizer
      第16回日本病態プロテアーゼ学会学術集会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪)
    • Year and Date
      20110826-20110827
  • [Presentation] Malfunction of HCN chanels in X11/X11L doubly deficient mice2011

    • Author(s)
      Saito, Y., Inoue, T., Suzuki, T.
    • Organizer
      Alzheimer's Association International Conference 2011
    • Place of Presentation
      Porte de Versailles (France)
    • Year and Date
      20110716-20110721
  • [Presentation] Molecular mechanism of JIP1b-mediated APP association to kinesin-1 in APP transport and metabolic regulation2011

    • Author(s)
      Chiba, K., 4名略., Suzuki, T.
    • Organizer
      Alzheimer's Association International Conference 2011
    • Place of Presentation
      Porte de Versailles (France)
    • Year and Date
      20110716-20110721
  • [Presentation] Enhanced amyloidogenic processing of APP in Alcadein-deficient mice2011

    • Author(s)
      Gotoh, N., 4名略., Suzuki, T.
    • Organizer
      Alzheimer's Association International Conference 2011
    • Place of Presentation
      Porte de Versailles (France)
    • Year and Date
      20110716-20110721
  • [Presentation] Quantification of plasma p3-Alcα level with sELISA systems2011

    • Author(s)
      Fang, J., 6名略., Suzuki, T.
    • Organizer
      Alzheimer's Association International Conference 2011
    • Place of Presentation
      Porte de Versailles (France)
    • Year and Date
      20110716-20110721
  • [Presentation] Alternative gamma-secretase processing in sporadic Alzheimer's disease suggested by p3-Alc peptide, metabolic product of Alcadein2011

    • Author(s)
      Hata, S., 4名略., Suzuki, T.
    • Organizer
      Alzheimer's Association International Conference 2011
    • Place of Presentation
      Porte de Versailles (France)
    • Year and Date
      20110716-20110721
  • [Presentation] APP metabolism in brain of Alcadein alpha CTF transgenic mice2011

    • Author(s)
      Kimura, A., 3名略., Suzuki, T
    • Organizer
      Alzheimer's Association International Conference 2011
    • Place of Presentation
      Porte de Versailles (France)
    • Year and Date
      20110716-20110721
  • [Presentation] Alcadeine epsilon-cleavage followed by gamma-cleavage2011

    • Author(s)
      Piao, Y., Hata, S., Suzuki, T.
    • Organizer
      Alzheimer's Association International Conference 2011
    • Place of Presentation
      Porte de Versailles (France)
    • Year and Date
      20110716-20110721
  • [Presentation] Intracellular trafficking and metabolism of APP regulated by novel function of X11L2011

    • Author(s)
      Suzuki, T.
    • Organizer
      Alzheimer's Association International Conference 2011
    • Place of Presentation
      Porte de Versailles (France)
    • Year and Date
      20110716-20110721
  • [Presentation] Increased levels of soluble p3-Alcadeinα in plasma of patients with Alzheimer's disease2011

    • Author(s)
      Kamogawa, K., Kohara, K., 10名略., Suzuki, T.
    • Organizer
      American Academy of Neurology 63rd AAN Annual meeting
    • Place of Presentation
      Hawai'I Convention Center (USA)
    • Year and Date
      20110409-20110416
  • [Book] Alzheimer's disease as a membrane-associated enzymopathy of β-amyloid precursor protein (APP) secretases, in "Lipids and Cellular Membranes in Amyloid Disease" (Eds by Jelinek, R.)2011

    • Author(s)
      Hata, S., Saito, Y., Suzuki, T.
    • Total Pages
      177-194
    • Publisher
      Wiley-VCH (ISBN : 978-3-527-32860-4)
  • [Remarks]

    • URL

      http://www.pharm.hokudai.ac.jp/shinkei/index.html

URL: 

Published: 2013-06-26  

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