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Analyses of the functional domains in sugar chains using neuronal growth cones

Planned Research

Project AreaDeciphering sugar chain-based signals regulating integrative neuronal functions
Project/Area Number 23110005
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

TOJIMA Takuro  国立研究開発法人理化学研究所, 脳科学総合研究センター, 研究員 (00373332)

Co-Investigator(Renkei-kenkyūsha) KAMIGUCHI Hiroyuki  理化学研究所, 脳科学総合研究センター, シニアチームリーダー (10233933)
KUBOYAMA Tomoharu  富山大学, 和漢医薬学総合研究所, 助教 (10415151)
Project Period (FY) 2011-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥99,320,000 (Direct Cost: ¥76,400,000、Indirect Cost: ¥22,920,000)
Fiscal Year 2015: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2014: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2013: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2012: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2011: ¥28,730,000 (Direct Cost: ¥22,100,000、Indirect Cost: ¥6,630,000)
Keywordsコンドロイチン硫酸 / ケラタン硫酸 / 軸索ガイダンス / 成長円錐 / cAMP / カルシウム / 糖鎖 / Ca2+ / コンドロイチン硫酸プロテオグリカン / dystrophic endball / 軸索再生 / パキシリン / 軸索伸長 / 硫酸化構造
Outline of Final Research Achievements

Proteoglycans are extracellular macromolecules composed of a core protein and one or more covalently attached glycosaminoglycan (GAG) sugar chain(s). Recent discoveries of cell-surface GAG receptors led us to propose a novel concept that sugar chains act as physiological ligands that evoke various cellular responses. However, little is known about the intracellular signaling mechanisms downstream of GAG receptors. In this study, we examined whether chondroitin sulfate (CS) and keratan sulfate (KS) GAG chains affect motilities of neuronal growth cones and what signaling mechanisms mediate the growth cone behaviors. We found that extracellular gradients of CS-E and high-sulfated KS repelled growth cones of dorsal root ganglion neurons. The repulsion was dependent on intracellular calcium, and converted into attraction in the presence of higher concentration of cAMP. These results indicate that GAG chains act as bidirectional axon guidance cues in the developing nervous system.

Report

(6 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (41 results)

All 2016 2015 2014 2013 2012 2011 Other

All Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Acknowledgement Compliant: 4 results) Presentation (21 results) (of which Invited: 8 results) Remarks (8 results)

  • [Journal Article] Cyclic nucleotide control of microtubule dynamics for axon guidance2016

    • Author(s)
      Hiroki Akiyama, Tetsuko Fukuda, Takuro Tojima, Viacheslav Nikolaev, Hiroyuki Kamiguchi
    • Journal Title

      Journal of Neuroscience

      Volume: 印刷中

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 損傷した神経回路は修復できるか2016

    • Author(s)
      戸島拓郎,上口裕之
    • Journal Title

      こころの科学

      Volume: 印刷中

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Exocytic and endocytic membrane trafficking in axon development2015

    • Author(s)
      Takuro Tojima, Hiroyuki Kamiguchi
    • Journal Title

      Development, Growth & Differentiation

      Volume: 57 Issue: 4 Pages: 291-304

    • DOI

      10.1111/dgd.12218

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Visualization of clathrin-mediated endocytosis during Semaphorin-guided axonal growth2015

    • Author(s)
      Rurika Itofusa, Takuro Tojima, Hiroyuki Kamiguchi.
    • Journal Title

      Methods in Molecular Biology

      Volume: 印刷中

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 成長円錐はどのように動くのか2015

    • Author(s)
      戸島拓郎,上口裕之
    • Journal Title

      Clinical Neuroscience

      Volume: 33 Pages: 474-475

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Steering neuronal growth cones by shifting the imbalance between exocytosis and endocytosis2014

    • Author(s)
      Takuro Tojima, Rurika Itofusa, Hiroyuki Kamiguchi
    • Journal Title

      Journal of Neuroscience

      Volume: 34 Issue: 21 Pages: 7165-7178

    • DOI

      10.1523/jneurosci.5261-13.2014

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Paxillin phosphorylation counteracts proteoglycan-mediated inhibition of axon regeneration2013

    • Author(s)
      Tomoharu Kuboyama, Xueting Luo, Kevin Park, Murray G. Blackmore, Takuro Tojima, Chihiro Tohda, John L. Bixby, Vance P. Lemmon, Hiroyuki Kamiguchi
    • Journal Title

      Experimental Neurology

      Volume: 248 Pages: 157-169

    • DOI

      10.1016/j.expneurol.2013.06.011

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular signaling and membrane trafficking control bidirectional growth cone guidance2012

    • Author(s)
      Takuro Tojima
    • Journal Title

      Neuroscience Research

      Volume: 73 Issue: 4 Pages: 269-274

    • DOI

      10.1016/j.neures.2012.05.010

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 神経軸索突起の進路決定メカニズム2012

    • Author(s)
      秋山博紀
    • Journal Title

      生化学

      Volume: 84 Pages: 848-853

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Second messengers and membrane trafficking direct and organize growth cone steering2011

    • Author(s)
      戸島拓郎
    • Journal Title

      Nature Reviews Neuroscience

      Volume: 12 Issue: 4 Pages: 191-203

    • DOI

      10.1038/nrn2996

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 神経軸索突起をターゲットへ導く細胞内メカニズム2011

    • Author(s)
      戸島拓郎
    • Journal Title

      生物物理

      Volume: 51 Pages: 214-217

    • NAID

      10029482440

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Current and future therapeutic strategies for functional repair of spinal cord injury2011

    • Author(s)
      Tohda C
    • Journal Title

      Pharmacology & Therapeutics

      Volume: 132 Issue: 1 Pages: 57-71

    • DOI

      10.1016/j.pharmthera.2011.05.006

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Signaling mechanisms of axon guidance induced by glycosaminoglycans2016

    • Author(s)
      Takuro Tojima
    • Organizer
      The 3rd International Symposium on Glyco-Neuroscience
    • Place of Presentation
      淡路夢舞台(兵庫)
    • Year and Date
      2016-01-14
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] サイクリックヌクレオチドは微小管依存的な先導端突出の制御を介して軸索の伸長方向を決定する2015

    • Author(s)
      秋山博紀,福田徹子,戸島拓郎,上口裕之
    • Organizer
      第38回日本分子生物学会年会第88回日本生化学会大会合同大会
    • Place of Presentation
      神戸国際会議場(兵庫)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 神経軸索ガイダンスの時空間制御機構2015

    • Author(s)
      戸島拓郎
    • Organizer
      広島大学インキュベーション研究拠点研究セミナー
    • Place of Presentation
      広島大学(広島)
    • Year and Date
      2015-10-07
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] グリコサミノグリカンと軸索ガイダンス2015

    • Author(s)
      戸島拓郎
    • Organizer
      日本医療研究開発機構(AMED)研究費 難治性疾患実用化研究事業「筋萎縮性側索硬化症(ALS)新規治療法開発をめざした病態解明」班ワークショップ
    • Place of Presentation
      都市センターホテル(東京)
    • Year and Date
      2015-09-25
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] グリコサミノグリカンによる神経軸索突起の誘導制御2015

    • Author(s)
      戸島拓郎
    • Organizer
      第34回日本糖質学会
    • Place of Presentation
      東京大学(東京)
    • Year and Date
      2015-08-02
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] グリコサミノグリカンによる軸索ガイダンスの制御機構2015

    • Author(s)
      戸島拓郎
    • Organizer
      第38回日本神経科学大会
    • Place of Presentation
      神戸国際会議場(兵庫)
    • Year and Date
      2015-07-29
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 神経細胞の運動におけるlasp-2のactin結合領域の機能2015

    • Author(s)
      寺崎朝子, 佐々木貴広, 石川達也, 中川裕之, 秋山博紀, 戸島拓郎, 上口裕之
    • Organizer
      第67回日本細胞生物学会大会
    • Place of Presentation
      タワーホール船堀(東京)
    • Year and Date
      2015-07-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Control of neuronal growth cone navigation by chondroitin sulfate2014

    • Author(s)
      Takuro Tojima
    • Organizer
      Joint Meeting of the Society for Glycobiology (SFG) and the Japanese Society of Carbohydrate Research (JSCR) (Satellite Symposium: Glycans in Neuroscience)
    • Place of Presentation
      Hilton Hawaiian Village (Honolulu, USA)
    • Year and Date
      2014-11-16
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Regulatory mechanisms of chondroitin sulfate-mediated axon guidance2014

    • Author(s)
      Masao Nakamura, Jun-ichi Tamura, Hiroshi Kitagawa, Takuro Tojima, Hiroyuki Kamiguchi
    • Organizer
      Joint Meeting of the Society for Glycobiology (SFG) and the Japanese Society of Carbohydrate Research (JSCR) (Satellite Symposium: Glycans in Neuroscience)
    • Place of Presentation
      Hilton Hawaiian Village (Honolulu, USA)
    • Year and Date
      2014-11-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] 神経軸索ガイダンスを制御する糖鎖作動原理2014

    • Author(s)
      戸島拓郎
    • Organizer
      第87回日本生化学会大会(シンポジウム)
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2014-10-15
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 神経突起ガイダンスを担うコンドロイチン硫酸Eの受容機構2014

    • Author(s)
      中村真男、田村純一、北川裕之、戸島拓郎、上口裕之
    • Organizer
      第33回日本糖質学会年会
    • Place of Presentation
      名古屋大学(愛知)
    • Year and Date
      2014-08-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] cAMP/cGMPによる微小管依存的小胞輸送の拮抗制御の成長円錐ガイダンスにおける役割2012

    • Author(s)
      秋山博紀
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Year and Date
      2012-09-18
    • Related Report
      2012 Annual Research Report
  • [Presentation] 神経軸索伸長を制御するコンドロイチン硫酸サブタイプの解析2012

    • Author(s)
      中村真男
    • Organizer
      包括脳ネットワーク夏のワークショップ
    • Place of Presentation
      仙台
    • Year and Date
      2012-07-26
    • Related Report
      2012 Annual Research Report
  • [Presentation] Ca2+ signaling and membrane trafficking mediate neuronal growth cone guidance2012

    • Author(s)
      Takuro Tojima
    • Organizer
      Joint Meeting of The 45th Annual Meeting of the Japanese Society of Developmental Biologists The 64th Annual Meeting of the Japan Society for Cell Biology
    • Place of Presentation
      Kobe
    • Year and Date
      2012-05-30
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] コンドロイチン硫酸プロテオグリカンによる軸索再生阻害のシグナル伝達機構2011

    • Author(s)
      久保山友晴
    • Organizer
      第54回日本神経化学会大会
    • Place of Presentation
      加賀
    • Year and Date
      2011-09-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] 神経軸索ガイダンスの方向極性を決定するカルシウム依存性エンドサイトーシス制御2011

    • Author(s)
      戸島拓郎
    • Organizer
      第34回日本神経科学大会
    • Place of Presentation
      横浜
    • Year and Date
      2011-09-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] Searching for natural medicines that improve spinal cord injury2011

    • Author(s)
      Wang X
    • Organizer
      28回和漢医薬学会学術大会
    • Place of Presentation
      富山
    • Year and Date
      2011-08-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] コンドロイチン硫酸による軸索伸長と誘導の制御機構

    • Author(s)
      中村真男、田村純一、北川裕之、戸島拓郎、上口裕之
    • Organizer
      第36回日本神経科学大会第56回日本神経化学会大会第23回日本神経回路学会大会合同大会(Neuro2013)
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] コンドロイチン硫酸による反発性神経軸索ガイダンスの調節機構

    • Author(s)
      中村真男、田村純一、北川裕之、戸島拓郎、上口裕之
    • Organizer
      第32回日本糖質学会年会
    • Place of Presentation
      大阪
    • Related Report
      2013 Annual Research Report
  • [Presentation] 軸索ガイダンスを制御する糖鎖受容機構の解明

    • Author(s)
      戸島拓郎
    • Organizer
      平成25年度 包括脳ネットワーク 夏のワークショップ
    • Place of Presentation
      名古屋
    • Related Report
      2013 Annual Research Report
  • [Presentation] Signaling mechanisms of neuronal growth cone guidance induced by chondroitin sulfate

    • Author(s)
      Takuro Tojima
    • Organizer
      International Symposium on Glyco-Neuroscience
    • Place of Presentation
      Hyogo
    • Related Report
      2013 Annual Research Report
  • [Remarks] 戸島拓郎の研究者個人ホームページ

    • Related Report
      2015 Annual Research Report
  • [Remarks] 戸島拓郎の研究者個人ホームページ

    • URL

      http://tojimat.web.fc2.com/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 脳科学総合研究センター神経成長機構研究チーム

    • URL

      http://www.riken.jp/research/labs/bsi/neur_growth_mech/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 脳科学総合研究センター神経成長機構研究チーム

    • URL

      http://www.riken.jp/research/labs/bsi/neur_growth_mech/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 戸島拓郎の研究者個人ホームページ

    • URL

      http://tojimat.web.fc2.com/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 戸島拓郎のホームページ

    • URL

      http://tojimat.web.fc2.com/

    • Related Report
      2012 Annual Research Report
  • [Remarks] 理化学研究所脳科学総合研究センター神経成長機構研究チーム

    • URL

      http://www.riken.go.jp/research/labs/bsi/neur_growth_mech/

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.brain.riken.jp/jp/faculty/details/21

    • Related Report
      2011 Annual Research Report

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Published: 2011-08-01   Modified: 2019-07-29  

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