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2013 Fiscal Year Final Research Report

Multi-functionality of dynamin family and mechanism of integrated control

Research Project

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Project/Area Number 23370089
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionOkayama University

Principal Investigator

TAKEI Kohji  岡山大学, 医歯(薬)学総合研究科, 教授 (40322226)

Co-Investigator(Kenkyū-buntansha) YAMADA Hiroshi  岡山大学, 大学院・医歯薬学総合研究科, 准教授 (80325092)
TANEBE Kenji  岡山大学, 大学院・医歯薬学総合研究科, 助教 (80423341)
Project Period (FY) 2011-04-01 – 2014-03-31
Keywordsダイナミン / コルタクチン / アクチン / 成長円錐 / フィロポディア / 阻害剤
Research Abstract

We have clarified a novel regulatory mechanism of actin dynamics by dynamin/cortactin complex. The complex is ring-shaped and it changed the conformation upon dynamin GTP hydrolysis, from open ring to close ring. By the open-cloze motion, the complex bundled F-actins and stabilized the actin bundles. Furthermore, we identified N'-[4-(dipropylamino)benzylidene]-2-hydroxybenzohydrazide(DBHA)as a dynamin inhibitor that suppress dynamin-dependent actin regulation. DBHA inhibited recruitment of dynamin to the leading edge of migrating cancer cell line and ruffle formation. It also showed inhibitory effect in cell migration, invasion, and proliferation.

  • Research Products

    (28 results)

All 2014 2013 2012 2011

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (16 results) Book (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] N'-[4-(dipropylamino)benzylidene]-2-hydroxybenzohydrazide is a dynamin GTPase inhibitor that suppresses cancer cell migration and invasion by inhibiting actin polymerization2013

    • Author(s)
      Yamada, H., Abe, T., Li, S.A., Tago, S., Huang, P., Watanabe, M., Ikeda, S., Ogo, N., Asai, A., Takei, K
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 443 Pages: 511-517

    • DOI

      10.1016/j.bbrc.2013.11.118

    • Peer Reviewed
  • [Journal Article] Stabilization of actin bundles by a dynamin 1/cortactin ring complex is necessary for growth cone filopodia2013

    • Author(s)
      Yamada, H., Abe, T., Satoh, A., Okazaki, N., Tago, S., Kobayashi, K., Yoshida, Y., Oda, Y., Watanabe, M., Tomizawa, K., Matsui, H., and Takei, K
    • Journal Title

      J Neurosci

      Volume: 33 Pages: 4514-4526

    • DOI

      10.1523/JNEUROSCI.2762-12.2013

    • Peer Reviewed
  • [Journal Article] REIC/Dkk-3-encoding adenoviral vector as a potentially effective therapeutic agent for bladder cancer2012

    • Author(s)
      Hirata, T., Watanabe, M., Kaku, H., Kobayashi, Y., Yamada, H., Sakaguchi, M., Takei, K., Huh, N.H., Nasu, Y, Kumon, H
    • Journal Title

      Int J Oncol

      Volume: 41 Pages: 559-564

    • DOI

      10.3892/ijo.2012.1503.Epub2012May31

    • Peer Reviewed
  • [Journal Article] A novel gene expression system for detecting viable bladder cancer cells2012

    • Author(s)
      Ueki, H., Watanabe, M., Kaku, H., Huang, P., Li, S.A., Ochiai, K., Hirata, T., Noguchi, H., Yamada, H., Takei, K., Nasu, Y, Kashiwakura Y, and Kumon H
    • Journal Title

      Int J Oncol

      Volume: 41 Pages: 135-140

    • Peer Reviewed
  • [Journal Article] The clathrin assembly protein PICALM is required for erythroid maturation and transferrin internalization in mice2012

    • Author(s)
      Suzuki, M., Tanaka, H., Tanimura, A., Tanabe, K., Oe, N., Rai, S., Kon, S., Fukumoto, M., Takei, K., Abe, T., Matsumura, I., Kanakura, Y., and Watanabe, T
    • Journal Title

      PLoS One 7

      Pages: e31854

    • DOI

      10.1371/journal.pone.0031854.Epub2012Feb21.

    • Peer Reviewed
  • [Journal Article] Receptor sorting within endosomal trafficking pathway is facilitated by dynamic actin filaments2011

    • Author(s)
      Ohashi, E., Tanabe, K., Henmi, Y., Mesaki, K., Kobayashi, Y., and Takei, K
    • Journal Title

      PLoS One 6

      Pages: e19942

    • DOI

      10.1371/journal.pone.0019942.Epub2011May20

    • Peer Reviewed
  • [Journal Article] Fission of tubular endosomes triggers endosomal acidification and movement2011

    • Author(s)
      Mesaki, K., Tanabe, K., Obayashi, M., Oe, N., and Takei, K
    • Journal Title

      PLoS One 6

      Pages: e19764

    • Peer Reviewed
  • [Journal Article] Dynamin 2 associates with microtubules at mitosis and regulates cell cycle progression2011

    • Author(s)
      Ishida, N., Nakamura, Y., Tanabe, K., Li, S.A., and Takei, K
    • Journal Title

      Cell Struct Funct 36

      Pages: 145-154

    • Peer Reviewed
  • [Journal Article] Disruption of microtubule network rescues aberrant actin comets in dynamin2-depleted cells2011

    • Author(s)
      Henmi, Y., Tanabe, K., and Takei, K
    • Journal Title

      PLoS One 6

      Pages: e28603

    • DOI

      10.1371/journal.pone.0028603.Epub2011Dec12

    • Peer Reviewed
  • [Presentation] 熱帯熱マラリア原虫ダイナミンGTPase の膜動態制御2014

    • Author(s)
      竹居孝二
    • Organizer
      第83回日本寄生虫学会大会
    • Place of Presentation
      愛媛大学
    • Year and Date
      20140327-28
  • [Presentation] 熱帯熱マラリア原虫ダイナミンGTPase の膜動態制御と構造機能相関2013

    • Author(s)
      山田浩司
    • Organizer
      「ライフサイエンスの革新を目指した構造生命科学と先端的基盤技術」研究領域 CREST/さきがけ合同キックオフミーティング及び研究成果報告会
    • Place of Presentation
      滋賀県守山市ラフォーレ琵琶湖
    • Year and Date
      20131219-20
  • [Presentation] ダイナミン GTP アーゼは生体膜とアクチン細胞骨格をメカニカルに制御する2013

    • Author(s)
      竹居孝二
    • Organizer
      「ライフサイエンスの革新を目指した構造生命科学と先端的基盤技術」研究領域CREST/さきがけ合同キックオフミーティング及び研究成果報告会
    • Place of Presentation
      滋賀県守山市ラフォーレ琵琶湖
    • Year and Date
      20131219-20
  • [Presentation] N'-(4-(dipropylamino)benzylidene)-2-hydroxybenzohydrazide is a dynamin GTPase inhibitor and suppresses cancer cell migration and invasion by inhibiting actin polymerization2013

    • Author(s)
      阿部匡史
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜市,パシフィコ横浜
    • Year and Date
      20130911-13
  • [Presentation] A novel mechanism of actin bundle formation supporting the formation of filopodia2013

    • Author(s)
      竹居孝二
    • Organizer
      第65回日本細胞生物学会大会
    • Place of Presentation
      名古屋市ウインクあいち
    • Year and Date
      20130619-21
  • [Presentation] Mechanochemical regulation of actin dynamics by a Dynamin 1 / Cortactin ring complex2013

    • Author(s)
      山田浩司
    • Organizer
      第5回日本生物物理学会中国四国支部大会
    • Place of Presentation
      香川県直島ベネッセハウス
    • Year and Date
      20130525-26
  • [Presentation] Dynamin GTPase / Cortactin ring complex is a mechanical devise stabilizing actin bundles2012

    • Author(s)
      竹居孝二
    • Organizer
      第38回生体エネルギー研究会
    • Place of Presentation
      岡山大学
    • Year and Date
      20121222-24
  • [Presentation] Dynamin を標的にした抗がん剤の開発2012

    • Author(s)
      岡崎奈奈
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場マリンメッセ福岡
    • Year and Date
      20121214-16
  • [Presentation] Phosphorylation of cortactin by PKC is a key factor for filopodia formation of growth cones2012

    • Author(s)
      山田浩司
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場マリンメッセ福岡
    • Year and Date
      20121214-16
  • [Presentation] ダイナミン 2 は微小管を介してアクチンコメットを制御する2012

    • Author(s)
      逸見祐次
    • Organizer
      第53回日本生化学会中国・四国支部例会
    • Place of Presentation
      岡山大学
    • Year and Date
      2012-05-18
  • [Presentation] ホスファチジルイノシトール-4-キナーゼ IIα は初期エンドソームにおける選別 輸送を制御する2012

    • Author(s)
      田邊賢司
    • Organizer
      第53回日本生化学会中国・四国支部例会
    • Place of Presentation
      岡山大学
    • Year and Date
      2012-05-18
  • [Presentation] PKC phosphorylation of cortactin is implicated in the regulation of actin dynamics2011

    • Author(s)
      竹居孝二
    • Organizer
      第51回米国細胞生物学会
    • Place of Presentation
      米国デンバー
    • Year and Date
      20111203-07
  • [Presentation] ダイナミン・コルタクチン複合体によるアクチン細胞骨格制御機構2011

    • Author(s)
      竹居孝二
    • Organizer
      第33回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      岡山大学
    • Year and Date
      20111124-25
  • [Presentation] Phosphorylation of Cortactin by PKC alpha is involved in formation of filopodia of growth cones2011

    • Author(s)
      山田浩司
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      20110921-24
  • [Presentation] Receptor Sorting Within Endosomal Trafficking Pathway Is Facilitated By Dynamic Actin Filaments2011

    • Author(s)
      逸見祐次
    • Organizer
      第63回日本細胞生物学会大会
    • Place of Presentation
      北海道大学
    • Year and Date
      20110627-29
  • [Presentation] Phosphatidylinositol 4-kinase II alpha is required for receptor sorting at early endosomes2011

    • Author(s)
      田邊賢司
    • Organizer
      第63回日本細胞生物学会大会
    • Place of Presentation
      北海道大学
    • Year and Date
      20110627-29
  • [Book] Etiological role of dynamin in Charcot-Marie-Tooth disease. "Peripheral Neuropathy - Advances in Diagnostic and Therapeutic Approaches"2012

    • Author(s)
      Takei, K. and Tanabe, K
    • Total Pages
      3-20
    • Publisher
      InTech (Rijeka, Croatia)
  • [Patent(Industrial Property Rights)] 抗浸潤薬の新規スクリーニング法および抗浸潤剤2012

    • Inventor(s)
      山田浩司, 竹居孝二, 道上宏之, 松井秀樹, 浅井章良
    • Industrial Property Rights Holder
      山田浩司, 竹居孝二, 道上宏之, 松井秀樹, 浅井章良
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      特願2012-137489
    • Filing Date
      2012-06-19
  • [Patent(Industrial Property Rights)] フルボキサミンを配合することを特徴とする分子標的型抗癌剤(特に抗脳腫瘍治療薬剤:第二医薬品用途)2012

    • Inventor(s)
      道上宏之, 林圭一郎, 松井秀樹, 山田浩司, 竹居孝二, 宮地弘幸, 浅井章良
    • Industrial Property Rights Holder
      道上宏之, 林圭一郎, 松井秀樹, 山田浩司, 竹居孝二, 宮地弘幸, 浅井章良
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      特願2012-263317
    • Filing Date
      2012-11-30

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Published: 2015-06-25  

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