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Identification down stream factors of tyrosine phosphatase which negatively regulate autophagy flux and axonal regeneration

Research Project

Project/Area Number 16K19049
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pathological medical chemistry
Research InstitutionNagoya University

Principal Investigator

Sakamoto Kazuma  名古屋大学, 医学系研究科, 助教 (60612801)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsオートファジー / コンドロイチン硫酸 / PTPRσ / 軸索再生 / リン酸化・脱リン酸化 / チロシンフォスファターゼ / シグナル伝達 / 再生医学 / 神経科学
Outline of Final Research Achievements

Upon injury, the distal terminal of axon transforms into so-called dystrophic endball. This degenerative structure has been thought to be closely associated with inability of regeneration of our axons in the cetral nervous system. However, underlying molecular mechanism except neuronal cell-surface molecule, PTPRσ, has been unknown. Here I have identified Cortactin as a new substrate for PTPRσ. Cortactin was de-phosphorylated by PTPRσ, and its phosphorylated form was completely diminished in dystrophic endball. Furthermore, knock-down of Cortactin in cultured neurons led to inhibition of axonal elongation, and swollen structures with autophagosomal accumulation which was specific character of dystrophic endball.
Taken together, these results have revealed a pivotal role of PTPRσ-Cortactin axis in axonal regeneration and its inhibition.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (12 results)

All 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Invited: 1 results)

  • [Int'l Joint Research] Academia Sinica(台湾)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Axonal autophagy and its disruption in human diseases2018

    • Author(s)
      坂元 一真、門松 健治
    • Journal Title

      生化学

      Volume: 90 Issue: 1 Pages: 27-34

    • DOI

      10.14952/SEIKAGAKU.2018.900027

    • ISSN
      0037-1017
    • Year and Date
      2018-02-25
    • Related Report
      2017 Annual Research Report
  • [Journal Article] Midkine Promotes Atherosclerotic Plaque Formation Through Its Pro-Inflammatory, Angiogenic and Anti-Apoptotic Functions in Apolipoprotein E-Knockout Mice2018

    • Author(s)
      Takemoto Y, Horiba M, Harada M, Sakamoto K, Takeshita K, Murohara T, Kadomatsu K, Kamiya K.
    • Journal Title

      Circulation Journal

      Volume: 82 Issue: 1 Pages: 19-27

    • DOI

      10.1253/circj.CJ-17-0043

    • NAID

      130006281926

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glycosaminoglycans and human diseases2017

    • Author(s)
      尾﨑 智也、坂元 一真、内村 健治、門松 健治
    • Journal Title

      生化学

      Volume: 89 Issue: 5 Pages: 689-698

    • DOI

      10.14952/SEIKAGAKU.2017.890689

    • ISSN
      0037-1017
    • Year and Date
      2017-10-25
    • Related Report
      2017 Annual Research Report
  • [Journal Article] Dissecting the interaction between tissue inhibitor of metalloproteinases-3 (TIMP-3) and low density lipoprotein receptor-related protein-1 (LRP-1): Development of a "TRAP" to increase levels of TIMP-3 in the tissue.2017

    • Author(s)
      Scilabra SD, Yamamoto K, Pigoni M, Sakamoto K, Muller SA, Papadopoulou A, Lichtenthaler SF, Troeberg L, Nagase H, Kadomatsu K.
    • Journal Title

      Matrix Biol.

      Volume: 59 Pages: 69-79

    • DOI

      10.1016/j.matbio.2016.07.004

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Mechanisms of axon regeneration: The significance of proteoglycans.2017

    • Author(s)
      Sakamoto K, Kadomatsu K.
    • Journal Title

      Biochim Biophys Acta.

      Volume: 1861 Issue: 10 Pages: 2435-2441

    • DOI

      10.1016/j.bbagen.2017.06.005

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neurocan, an extracellular chondroitin sulfate proteoglycan, stimulates neuroblastoma cells to promote malignant phenotypes.2017

    • Author(s)
      1.Su Z, Kishida S, Tsubota S, Sakamoto K, Cao D, Kiyonari S, Ohira M, Kamijo T, Narita A, Xu Y, Takahashi Y, Kadomatsu K.
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 63 Pages: 106296-106310

    • DOI

      10.18632/oncotarget.22435

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Dystrophic endball形成の細胞生物学的基盤2018

    • Author(s)
      坂元一真 門松健治
    • Organizer
      第123回日本解剖学会総会・全国学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 糖鎖中の硫酸化パターンの頻度が損傷後の軸索運命を決定する2017

    • Author(s)
      坂元一真 尾崎智也 キョウエンコウ 田村純一 Shang-Cheng Hung 門松健治
    • Organizer
      新学術領域研究 「神経糖鎖生物学」 最終班会議
    • Place of Presentation
      名古屋JPタワー(愛知県名古屋市)
    • Year and Date
      2017-03-03
    • Related Report
      2016 Research-status Report
  • [Presentation] Probability of glycan sulfation patterns determines axonal fate after injury2017

    • Author(s)
      Kazuma Sakamoto Ozaki Tomoya Yuanhao Gong  Jun-ichi Tamura Hung Shang-Cheng Kenji Kadomatsu
    • Organizer
      第40回神経科学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Dystrophic endballは autophagy fluxの停滞により形成され、中枢神経軸索再生を阻害する2016

    • Author(s)
      坂元一真 尾崎智也  Gong Yuanhao  田村純一 門松健治
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター 東北大学(宮城県仙台市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] Frequency and length of sugar codes in sulfated glycans regulate axonal regneration and its failure2016

    • Author(s)
      Kazuma Sakamoto, Tomoya Ozaki, Yuanhao Gong, Kenji Kadomatsu
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2022-02-22  

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