Analysis on the centrosomal functions of neural dendrites - microtubule nucleation and minus-end anchoring

• Project/Area Number: 17K07083
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Sophia University
• Principal Investigator: HAYASHI Kensuke 上智大学, 理工学部, 教授 (50218567)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 脳の発達 / 神経細胞 / 樹状突起 / 微小管 / 中心体 / 物質輸送 / ニューロン / 細胞・組織 / 脳・神経 / 発生・分化 / 神経科学

Outline of Final Research Achievements

Microtubules must increase in number for dendrite growth. The centrosome of a neuron lacks the ability to form microtubules, and it has been unclear where microtubules are produced in neurons. In this study, we showed that microtubules are nucleated in the cytoplasm in neurons. Furthermore, we found a neuron-specific alternative splicing isoform of CDK5RAP2, as a protein that activates microtubule formation in the cytoplasm of neurons. In cells expressing this isoform, microtubule formation was induced in the cytoplasm. These results indicate that selective splicing of CDK5RAP2 is involved in the increase of microtubules in developing neurons.

Academic Significance and Societal Importance of the Research Achievements

脳の発達に必要な、神経細胞の樹状突起の成長をコントロールする新しい仕組みが明らかになった。この仕組みを応用して、脳の機能発達に介入するあたらしい技術の開発への道を開いた。

Research Products

• [Journal Article] The difference in the cytoskeletal machinery of growth cones of growing axons and leading processes (2022)
  • Author(s): Miyata Kaho、Hayashi Kensuke
  • Journal Title: Developmental Neuroscience Volume: 1 Issue: 6 Pages: 1-1
  • DOI: 10.1159/000522200
  • Peer Reviewed
• [Journal Article] The Golgi apparatus is the main microtubule-organizing center in differentiating skeletal muscle cells (2021)
  • Author(s): Ide Koyo、Muko Mika、Hayashi Kensuke
  • Journal Title: Histochemistry and Cell Biology Volume: 156 Issue: 3 Pages: 273-281
  • DOI: 10.1007/s00418-021-01999-6
  • Peer Reviewed
• [Journal Article] Discovery of a Potent Anticancer Agent PVHD303 with in Vivo Activity (2020)
  • Author(s): Suzuki Yumiko、Otake Ayana、Ueno Satoshi、Hayashi Kensuke、Ishii Hirosuke、Miyoshi Nao、Kuroiwa Kenta、Tachikawa Masashi、Fujimaki Yuki、Nishiyama Kotaro、Manabe Kei、Yamazaki Ryuta、Asai Akira
  • Journal Title: ACS Medicinal Chemistry Letters Volume: 11 Issue: 6 Pages: 1287-1291
  • DOI: 10.1021/acsmedchemlett.0c00119
  • Peer Reviewed
• [Journal Article] Microtubule nucleation in the cytoplasm of developing cortical neurons and its regulation by brain‐derived neurotrophic factor (2019)
  • Author(s): Yamada Mimori、Hayashi Kensuke
  • Journal Title: Cytoskeleton Volume: 76 Issue: 5 Pages: 339-345
  • DOI: 10.1002/cm.21550
  • Peer Reviewed
• [Journal Article] KATNAL1 is a more active and stable isoform of katanin, and is expressed dominantly in neurons (2018)
  • Author(s): Hatakeyama Eiko、Hayashi Kensuke
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 507 Issue: 1-4 Pages: 389-394
  • DOI: 10.1016/j.bbrc.2018.11.048
  • Peer Reviewed
• [Journal Article] Changes in the axo-glial junctions of the optic nerves of cuprizone-treated mice (2018)
  • Author(s): Wataru Kojima and Kensuke Hayashi
  • Journal Title: Histochemistry and Cell Biology Volume: 印刷中
  • Peer Reviewed
• [Presentation] Difference between two katanin isoforms in the neuronal expression and ubiquitination (2020)
  • Author(s): Suzuki S. and Hayashi K.
  • Organizer: 日本分子生物学会
• [Presentation] Interaction between cytosolic dynein and neuronal cytosolic isoform of microtubule anchoring protein, ninein. (2020)
  • Author(s): Nakayama M. and Hayashi K.
  • Organizer: 日本分子生物学会
• [Presentation] ニューロンの細胞質からの微小管形成と微小管形成タンパクCDK5RAP2のエキソンスキップ (2019)
  • Author(s): 中村 朱里 林 謙介
  • Organizer: 分子生物学会
• [Presentation] 軸索突起の伸長と先導突起の移動におけるフィロポディアおよびラメリポディアの役割 (2019)
  • Author(s): 宮田夏帆 林謙介
  • Organizer: 分子生物学会
• [Presentation] Changes of microtubule arrangement induced by neuron-specific ninein isoform (2018)
  • Author(s): Moeka Hara and Kensuke Hayashi
  • Organizer: 日本分子生物学会
• [Presentation] 筋細胞の分化過程におけるゴルジ体からの微小管形成 (2018)
  • Author(s): 井出晃陽、林謙介
  • Organizer: 日本動物学会関東支部大会
• [Presentation] ニューロンの細胞質で微小管を形成するgamma-TuRC (2018)
  • Author(s): 山田美森、林謙介
  • Organizer: 日本動物学会関東支部大会
• [Presentation] 神経の発生における微小管切断酵素katanin A-like1の役割 (2018)
  • Author(s): 畠山瑛子、林謙介
  • Organizer: 日本動物学会関東支部大会
• [Presentation] ニューロン特異的nineinアイソフォームの発現と機能 (2018)
  • Author(s): 原 萌夏、林 謙介
  • Organizer: 日本動物学会関東支部大会
• [Presentation] 神経細胞の微小管形成とCDK5RAP2スプライシングバリアント (2018)
  • Author(s): 中村朱里、林 謙介
  • Organizer: 日本動物学会関東支部大会
• [Presentation] 移動性ニューロンの先導突起形成におけるdrebrinの働き (2018)
  • Author(s): 宮田夏帆、林 謙介
  • Organizer: 日本動物学会関東支部大会
• [Presentation] Changes in the microtubule organizing center during differentiation of muscle cells (2017)
  • Author(s): Koyo Ide, Kensuke Hayashi
  • Organizer: 日本分子生物学会
• [Presentation] Microtubule nucleation in the cytoplasm of developing neurons (2017)
  • Author(s): M. Yamada , K. Hayashi
  • Organizer: 日本分子生物学会
• [Presentation] Characterization of microtubule severing enzyme, katanin A-like1, highly expressed in neurons (2017)
  • Author(s): E. Hatakeyama and K. Hayashi
  • Organizer: 日本分子生物学会