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Explore of unconventional microtubules

Research Project

Project/Area Number 17H04047
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionOsaka City University

Principal Investigator

Hirotsune Shinji  大阪市立大学, 大学院医学研究科, 教授 (80337526)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywords細胞骨格 / 神経発生 / 神経変性疾患 / 細胞内物質輸送 / 神経細胞 / 中枢神経系 / 微小管 / 細胞質ダイニン / 神経科学
Outline of Final Research Achievements

We demonstrated that αSyn-bound tMTs carrying 14pfs, was confirmed by immuno-TEM analysis. This is the first evidence that shows the distinctive function of MTs with unconventional pfs numbers. Although in vitro tubulin polymerization yields MTs comprising 15pfs, the MTs in mammalian cells were previously thought to exclusively contain 13-pfs 6. MTs carrying 14pfs yield a helical arrangement 60 that is unsuitable for kinesin1 movement. However, tMTs would not be used for regular cytoskeletal MTs, as they are too small to provide a trafficking rail for motor proteins. Rather, tMTs are used as a transport platform to the periphery for proteins such as cytoplasmic dynein and the dynactin complex for which a helical pfs arrangement is not disadvantageous. It is worth exploring the distinctive functions of unconventional MTs through the identification of MAPs that can recognize MTs with unconventional pfs numbers.

Academic Significance and Societal Importance of the Research Achievements

非定型微小管の進化と神経機能の高度化の研究は高度な神経機能をもつヒトの中枢神経研究に多大な示唆を与えることが期待される。さらに非定型微小管が神経の部位によってどのような特殊性を持っているのかの解析、たとえば運動神経と感覚神経でどのように異なっているのかの解明はALSの病態生理の解明に資することが期待される。さらに中枢神経系の部位特異的なパターンの解析はその領域での軸索伸展やネットワーク形成の制御の解明につながることが期待される一方、その機構の破綻は神経変性疾患や精神神経疾患の病態解明や新たな治療戦略の創出につながることが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (4 results)

All 2020 2017

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 4 results)

  • [Journal Article] Enhanced homologous recombination by the modulation of targeting vector ends2020

    • Author(s)
      Shinji Hirotsune, Hiroshi Kiyonari、Mingyue Jin, Kanako Kumamoto, Kayo Yoshida, Miki Shinohara, Hitomi Watanabe, Anthony Wynshaw-Boris, Fumio Matsuzaki
    • Journal Title

      Scientific Reports

      Volume: 10 Pages: 58893-58899

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Alpha-synuclein facilitates to form short unconventional microtubules that have a unique function in the axonal transport2017

    • Author(s)
      Toba Shiori、Jin Mingyue、Yamada Masami、Kumamoto Kanako、Matsumoto Sakiko、Yasunaga Takuo、Fukunaga Yuko、Miyazawa Atsuo、Fujita Sakiko、Itoh Kyoko、Fushiki Shinji、Kojima Hiroaki、Wanibuchi Hideki、Arai Yoshiyuki、Nagai Takeharu、Hirotsune Shinji
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 16386-16386

    • DOI

      10.1038/s41598-017-15575-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Developmental downregulation of LIS1 expression limits axonal extension and allows axon pruning2017

    • Author(s)
      Kumamoto Kanako、Iguchi Tokuichi、Ishida Ryuichi、Uemura Takuya、Sato Makoto、Hirotsune Shinji
    • Journal Title

      Biology Open

      Volume: 6 Pages: 1041-1055

    • DOI

      10.1242/bio.025999

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Katanin p80, NuMA and cytoplasmic dynein cooperate to control microtubule dynamics2017

    • Author(s)
      Mingyue Jin, Oz Pomp, Tomoyasu Shinoda, Shiori Toba, Takayuki Torisawa, Ken’ya Furuta, Kazuhiro Oiwa, Takuo Yasunaga, Daiju Kitagawa, Shigeru Matsumura, Takaki Miyata, Thong Teck Tan, Bruno Reversade & Shinji Hirotsune
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 39902-39902

    • DOI

      10.1038/srep39902

    • NAID

      120005997787

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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