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Mechanisms and roles of microtubule generation in cells

Research Project

Project/Area Number 20687013
Research Category

Grant-in-Aid for Young Scientists (A)

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

Principal Investigator

GOSHIMA Gohta  Nagoya University, 理学研究科, 教授 (20447840)

Project Period (FY) 2008 – 2011
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥26,260,000 (Direct Cost: ¥20,200,000、Indirect Cost: ¥6,060,000)
Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2009: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2008: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Keywords細胞 / 組織 / 細胞、組織
Research Abstract

Microtubules are dynamic polymers made from α/β-tubulin dimers, and are crucial for various cellular events such as cell division, motility or organelle transport. Since the discovery of γ-tubulin, attention has been focused upon its role as a microtubule nucleator at the centrosome. However, recent observations revealed that spindle microtubules can also be generated by non-centrosomal pathways. A prior RNAi screen in Drosophila S2 cells identified 8 novel genes (Dgt2-9) that are required for localizing γ-tubulin to spindle microtubules. We showed that the Dgt proteins interact, forming a stable complex, which we named "augmin". Reduced spindle microtubule generation after augmin RNAi, particularly in the absence of functional centrosomes, has dramatic consequence on mitotic spindle formation and function, causing reduced kinetochore-fiber formation, chromosome misalignment, and spindle bipolarity defects. We also identified the human augmin complex of 8 subunits and showed that it in … More teracts with the γ-tubulin ring complex (γ-TuRC). A link between augmin and γ-TuRC is likely critical for these functions, since mutants of augmin or γ-TuRC that attenuate their interaction did not restore function in vivo. Our results suggested that γ-tubulin's most important mitotic function may lie within the spindle, where augmin and γ-tubulin function cooperatively to amplify the number of microtubules. In human cells, we also showed that augmin-dependent de novo microtubule generation in the interchromosomal region during anaphase is important for central spindle formation. Generation of interchromosomal microtubules and subsequent formation of the central spindle occurred independently of pre-anaphase microtubules or centrosomal microtubule nucleation. Based upon these results, a new model for central spindle assembly was proposed. Finally, we identified a novel protein "Sentin" that is localized at the growing end of microtubules via binding to EB1 protein. Sentin depletion in Drosophila S2 cells, similar to EB1 depletion, resulted in the increase in microtubule pausing and led to the formation of shorter spindles, without displacing EB1 from growing microtubules. We demonstrated that Sentin's association with EB1 is critical for its plus-end localisation and function; furthermore, the EB1 phenotype was rescued by expressing an EBN-Sentin fusion protein in which the C-terminal cargo-binding region of EB1 was replaced with Sentin. These results indicated that EB1 promotes dynamic microtubule behavior by recruiting the cargo protein Sentin to the microtubule tip. Less

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (47 results)

All 2011 2010 2009 2008 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (21 results) Book (8 results) Remarks (4 results)

  • [Journal Article] EB1 promotes microtubule dynamics by recruiting Sentin in Drosophila cells2011

    • Author(s)
      Li W, Watanabe T, Miki T, Kakeno M, Sugiyama I, Kaibuchi K, Goshima G.
    • Journal Title

      J Cell Biol 印刷中

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] New look inside the spindle:microtubule-dependent microtubule generation within the spindle.2010

    • Author(s)
      Goshima G, Kimura A.
    • Journal Title

      Curr Opin Cell Biol 22(1)

      Pages: 44-49

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional central spindle assembly requires de novo microtubule generation in the interchromosomal region during anaphase.2010

    • Author(s)
      Uehara R, Goshima G.
    • Journal Title

      J Cell Biol 191

      Pages: 259-267

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Control of mitotic spindle length2010

    • Author(s)
      Goshima G, Scholey, JM
    • Journal Title

      Annu Rev Cell Dev Biol 26巻

      Pages: 21-57

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Determinants of myosin II cortical localization during cytokinesis.2010

    • Author(s)
      Uehara R, Goshima G, Mabuchi I, Vale RD, Spudich JA, Griffis ER
    • Journal Title

      Curr Biol 20

      Pages: 1080-1085

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional central spindle assembly requires de novo microtubule generation in the interchromosomal region during anaphase.2010

    • Author(s)
      Uehara R, Goshima G.
    • Journal Title

      J Cell Biol

      Volume: 191 Pages: 259-267

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Control of mitotic spindle length2010

    • Author(s)
      Goshima G, Scholey, JM
    • Journal Title

      Annu Rev Cell Dev Biol

      Volume: 26 Pages: 21-57

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Determinants of myosin II cortical localization during cytokinesis.2010

    • Author(s)
      Uehara R, Goshima G, Mabuchi I, Vale RD, Spudich JA, Griffis ER
    • Journal Title

      Curr Biol

      Volume: 20 Pages: 1080-1085

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] New look inside the spindle : microtubule-dependent microtubule generation within the spindle.2010

    • Author(s)
      Goshima G, Kimura A.
    • Journal Title

      Curr Opin Cell Biol 22(1)

      Pages: 44-49

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The augmin complex plays a critical role in spindle microtubule generation for mitotic progression and cytokinesis in human cells2009

    • Author(s)
      R Uehara, R Nozawa,A Tomioka, S Petry, RD Vale, C Obuse, Goshima G
    • Journal Title

      Proc Natl Acad Sci USA 106(17)

      Pages: 6998-7003

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The augmin complex plays a critical role in spindle microtubule generation for mitotic progression and cytokinesis in human cells.2009

    • Author(s)
      R Uehara, R Nozawa, A Tomioka, S Petry, RD Vale, C Obuse, G Goshima
    • Journal Title

      Proc Natl Acad Sci USA 106(17)

      Pages: 6998-7003

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Augmin : a protein complex required for centrosome-independent microtubule generation within the spindle2008

    • Author(s)
      Goshima G, Mayer M, Zhang N, Stuurman, Vale RD
    • Journal Title

      J Cell Biol 5;181(3)

      Pages: 421-429

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional genomic screen reveals genes involved in lipid droplet formation and utilization.2008

    • Author(s)
      Guo Y, Walther TC, Rao M, Stuurman N, Goshima G, Terayama K, Wong JS, Vale RD, Walter P, Farese Jr RV.
    • Journal Title

      Nature 9;453(7195)

      Pages: 657-661

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The augmin complex plays a critical role in spindle microtubule generation for mitotic progression and cytokinesis in human cells.

    • Author(s)
      Uehara R, Nozawa R, Tomioka A, Petry S, Vale RD, Obuse C, Goshima G
    • Journal Title

      Proc Natl Acad Sci USA in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] Mechanism of microtubule generation during cell division2010

    • Author(s)
      Goshima G
    • Organizer
      20^<th> Hot Spring Harbor Symposium
    • Place of Presentation
      Fukuoka, Japan
    • Year and Date
      2010-08-20
    • Related Report
      2010 Annual Research Report
  • [Presentation] Mechanisms of microtubule nucleation and growth in cells2010

    • Author(s)
      Goshima G
    • Organizer
      EMBO conference : Microtubules- structure, function
    • Place of Presentation
      Heidelberg, Germany
    • Year and Date
      2010-06-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] Mechanisms of microtubule nucleation and growth in cells2010

    • Author(s)
      Goshima G
    • Organizer
      EMBO conference : Microtubules-structure, function
    • Place of Presentation
      Heidelberg, Germany
    • Year and Date
      2010-06-04
    • Related Report
      2009 Annual Research Report
  • [Presentation] 微小管形成機構研究のための新モデル植物2010

    • Author(s)
      五島剛太
    • Organizer
      第62回 日本細胞生物学会年会
    • Place of Presentation
      大阪
    • Year and Date
      2010-05-19
    • Related Report
      2010 Annual Research Report
  • [Presentation]2010

    • Organizer
      20^<th> Hot Spring Harbor Symposium
    • Place of Presentation
      福岡
    • Related Report
      2010 Final Research Report
  • [Presentation]2010

    • Organizer
      EMBOconference : Microtubules-structure, function
    • Place of Presentation
      ドイツ(ハイデルベルグ)
    • Related Report
      2010 Final Research Report
  • [Presentation]2010

    • Organizer
      第62回日本細胞生物学会
    • Place of Presentation
      大阪
    • Related Report
      2010 Final Research Report
  • [Presentation] A New Model Organism for Studying Microtubule Self-Organisation2009

    • Author(s)
      G.Goshima, Y.Nakaoka, M.Kubo, M.Hasebe, Y.Hiwatashi
    • Organizer
      THE AMERICAN SOCIETY FOR CELL BIOLOGY 49th Annua Meeting
    • Place of Presentation
      アメリカ、サンディアゴ
    • Year and Date
      2009-12-07
    • Related Report
      2008 Annual Research Report
  • [Presentation] Augmin Is Required for De Novo Microtubule Generation during Central Spindle Formation2009

    • Author(s)
      R Uehara, G Goshima
    • Organizer
      THE AMERICAN SOCIETY FOR CELL BIOLOGY 49th Annua Meeting
    • Place of Presentation
      アメリカ、サンディアゴ
    • Year and Date
      2009-12-07
    • Related Report
      2008 Annual Research Report
  • [Presentation] 細胞分裂期スピンドルの形成機構2009

    • Author(s)
      五島剛太
    • Organizer
      生化学若い研究者の会
    • Place of Presentation
      京都府、京都市
    • Year and Date
      2009-11-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] Microtubule generation within the spindle2009

    • Author(s)
      Gohta Goshima
    • Organizer
      2009 FASEB Summer Research Conference
    • Place of Presentation
      イタリア、ルッカ
    • Year and Date
      2009-09-04
    • Related Report
      2008 Annual Research Report
  • [Presentation] Genome-Wide RNAi Screen Identifies Genes Required for Mitotic Spindle Formation in Animal Cells2009

    • Author(s)
      Gohta Goshima
    • Organizer
      The Ninth NIBB-EMBL Symposium
    • Place of Presentation
      愛知県、岡崎市
    • Year and Date
      2009-04-21
    • Related Report
      2008 Annual Research Report
  • [Presentation]2009

    • Organizer
      The Ninth NIBB-EMBL Symposium
    • Place of Presentation
      愛知(岡崎)
    • Related Report
      2010 Final Research Report
  • [Presentation]2009

    • Organizer
      2009 FASEB Summer Research Conference
    • Place of Presentation
      イタリア(ルッカ)
    • Related Report
      2010 Final Research Report
  • [Presentation]2009

    • Organizer
      生化学若い研究者の会
    • Place of Presentation
      京都
    • Related Report
      2010 Final Research Report
  • [Presentation]2009

    • Organizer
      THE AMERICAN SOCIETY FOR CELL BIOLOGY 49^<th> Annua Meeting
    • Place of Presentation
      アメリカ
    • Related Report
      2010 Final Research Report
  • [Presentation]2008

    • Organizer
      第60回日本細胞生物学会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation]2008

    • Organizer
      第80回日本遺伝学会
    • Place of Presentation
      名古屋
    • Related Report
      2010 Final Research Report
  • [Presentation]2008

    • Organizer
      第79回日本動物学会
    • Place of Presentation
      福岡
    • Related Report
      2010 Final Research Report
  • [Presentation]2008

    • Organizer
      第2回国際「生体ナノシステムの制御」国際シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation]2008

    • Organizer
      米国細胞生物学会
    • Place of Presentation
      サンフランシスコ
    • Related Report
      2010 Final Research Report
  • [Book] Methods in Cell Biology, Elsevier Microtubules in vivo : Chapter 15 "Assessment of mitotic spindle phenotypes in Drosophila S2 cells."2010

    • Author(s)
      Goshima G
    • Total Pages
      17
    • Publisher
      Elsevier
    • Related Report
      2010 Final Research Report
  • [Book] 分裂期スピンドル形成における微小管生成機構2010

    • Author(s)
      五島剛太, 他
    • Total Pages
      5
    • Publisher
      細胞工学(学研メディカル秀潤社)
    • Related Report
      2010 Final Research Report
  • [Book] Microtubules in vivo : Chapter 15 "Assessment of mitotic spindle phenotypes in Drosophila S2 cells."2010

    • Author(s)
      Goshima G
    • Total Pages
      17
    • Publisher
      Methods in Cell Biology, Elsevier
    • Related Report
      2010 Annual Research Report
  • [Book] 分裂期スピンドル形成における微小管生成機構2010

    • Author(s)
      上原亮太 五島剛太
    • Total Pages
      5
    • Publisher
      細胞工学(学研メディカル秀潤社)
    • Related Report
      2010 Annual Research Report
  • [Book] Mitosis : Methods and Protocols, Methods in Molecular Biology 545 Chapter3 : RNAi in Drosophila S2 Cells as a Tool for Studying Cell Cycle Progression2009

    • Author(s)
      Monica Bettencourt-Dias, Gohta G oshima
    • Publisher
      Humana Press
    • Related Report
      2010 Final Research Report
  • [Book] 蛋白質核酸酵素11月号Vol.54 No.142009

    • Author(s)
      五島剛太, 他
    • Publisher
      共立出版
    • Related Report
      2010 Final Research Report
  • [Book] Mitosis : Methods and Protocols, Methods in Molecular Biology 545 Chapter3 : RNAi in Drosophila S2 Cells as a Tool for Studying Cell Cycle Progression2009

    • Author(s)
      Monica Bettencourt-Dias, Gohta Goshima
    • Publisher
      Humana Press
    • Related Report
      2008 Annual Research Report
  • [Book] 蛋白質核酸酵素 2009年11月号 Vol.54 No.142009

    • Author(s)
      上原亮太・五島剛太
    • Publisher
      共立出版
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://bunshi4.bio.nagoya-u.ac.jp/~tenure2/goshima.html

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://bunshi4.bio.nagoya-u.ac.jp/~tenure2/goshima.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://bunshi4.bio.nagoya-u.ac.jp/~tenure2/goshima.html

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://bunshi4.bio.nagoya-u.ac.jp/~tenure2/goshima.html

    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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