Analysis of svh genes regulating axon regeneration

• Project/Area Number: 17H03544
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Nagoya University
• Principal Investigator: Hisamoto Naoki 名古屋大学, 理学研究科, 教授 (80283456)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); 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: 軸索再生 / C. elegans / 神経軸索再生 / C.エレガンス / svh / 神経科学 / C. エレガンス

Outline of Final Research Achievements

Nerves have long projections called axons, and when they are physically severed, various neurological disorders occur. Many nerves have the ability to regenerate severed axons, but the molecular mechanisms that induce regeneration are only partially understood. In this study, we attempted to identify and analyze the novel factors that regulate axon regeneration using the model organism C. elegans. As a result, we identified many regulatory factors, including several svh genes, and clarified their functions and roles in axon regeneration.

Academic Significance and Societal Importance of the Research Achievements

本研究では、線虫をモデル動物として、神経軸索再生を制御する複数の因子、およびそれらが制御する複数のシグナル伝達経路について明らかにした。神経軸索再生機構の種を超えて保存された機構の解明は、脊髄損傷をはじめとする神経損傷を回復させる方法を開発するために必要な基礎生物学的知見であるという意味で、社会的にも重要な研究である。今回の研究で新たに明らかになった因子はほぼ全てがヒトにも存在することから、本研究成果が神経損傷治療につながる研究の礎になることが期待される。

Research Products

• [Int'l Joint Research] DBS-TIFR(インド)
• [Journal Article] C. elegans Tensin Promotes Axon Regeneration by Linking the Met-like SVH-2 and Integrin Signaling Pathways (2019)
  • Author(s): Hisamoto Naoki、Shimizu Tatsuhiro、Asai Kazuma、Sakai Yoshiki、Pastuhov Strahil I.、Hanafusa Hiroshi、Matsumoto Kunihiro
  • Journal Title: The Journal of Neuroscience Volume: 39 Issue: 29 Pages: 5662-5672
  • DOI: 10.1523/jneurosci.2059-18.2019
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] TDP2 Negatively Regulates Axon Regeneration by Inducing SUMOylation of an Ets Transcription Factor (2019)
  • Author(s): Sakai Yoshiki、Hanafusa Hiroshi、Pastuhov Strahil Iv、Shimizu Tatsuhiro、Li Chun、Hisamoto Naoki、Matsumoto Kunihiro
  • Journal Title: EMBO reports Volume: 20 Issue: 10
  • DOI: 10.15252/embr.201847517
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] N-Glycosylation of the Discoidin Domain Receptor Is Required for Axon Regeneration in Caenorhabditis elegans (2019)
  • Author(s): Shimizu Tatsuhiro、Kato Yuka、Sakai Yoshiki、Hisamoto Naoki、Matsumoto Kunihiro
  • Journal Title: Genetics Volume: 213 Issue: 2 Pages: 491-500
  • DOI: 10.1534/genetics.119.302492
  • Peer Reviewed / Open Access
• [Journal Article] LRRK1 phosphorylation of Rab7 at S72 links trafficking of EGFR-containing endosomes to its effector RILP (2019)
  • Author(s): Hanafusa Hiroshi、Yagi Takuya、Ikeda Haruka、Hisamoto Naoki、Nishioka Tomoki、Kaibuchi Kozo、Shirakabe Kyoko、Matsumoto Kunihiro
  • Journal Title: Journal of Cell Science Volume: 132 Issue: 11
  • DOI: 10.1242/jcs.228809
  • Peer Reviewed / Open Access
• [Journal Article] Phosphatidylserine exposure mediated by ABC transporter activates the integrin signaling pathway promoting axon regeneration. (2018)
  • Author(s): Hisamoto, N., Tsuge, A., Pastuhov, S., Shimizu, T., Hanafusa, H., Matsumoto, K.
  • Journal Title: Nature Commun. Volume: 9 Issue: 1 Pages: 3099-3099
  • DOI: 10.1038/s41467-018-05478-w
  • Peer Reviewed / Open Access
• [Journal Article] The C. elegans BRCA2‐ALP/Enigma complex regulates axon regeneration via a Rho GTPase- ROCK-MLC phosphorylation pathway (2018)
  • Author(s): Shimizu, T., Pastuhov, S., Matsumoto, K., Hisamoto, N.
  • Journal Title: Cell Rep. Volume: 24 Issue: 7 Pages: 1880-1889
  • DOI: 10.1016/j.celrep.2018.07.049
  • Peer Reviewed / Open Access
• [Journal Article] UNC-16/JIP3 regulates early events in synaptic vesicle protein trafficking via LRK-1/LRRK2 and AP complexes (2017)
  • Author(s): Choudhary Bikash、Kamak Madhushree、Ratnakaran Neena、Kumar Jitendra、Awasthi Anjali、Li Chun、Nguyen Ken、Matsumoto Kunihiro、Hisamoto Naoki、Koushika Sandhya P.
  • Journal Title: PLOS Genetics Volume: 13 Issue: 11 Pages: 1-25
  • DOI: 10.1371/journal.pgen.1007100
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Heavy Metal Stress Assay of Caenorhabditis elegans (2017)
  • Author(s): Pastuhov Strahil、Shimizu Tatsuhiro、Hisamoto Naoki
  • Journal Title: BIO-PROTOCOL Volume: 7 Issue: 11 Pages: 2312-2312
  • DOI: 10.21769/bioprotoc.2312
  • Peer Reviewed / Open Access
• [Journal Article] Signal transduction cascades in axon regeneration: insights from C. elegans (2017)
  • Author(s): Hisamoto Naoki、Matsumoto Kunihiro
  • Journal Title: Curr. Opin. Genet. Dev. Volume: 44 Pages: 54-60
  • DOI: 10.1016/j.gde.2017.01.010
  • Peer Reviewed / Open Access
• [Presentation] Phosphatidylserine exposure mediated by ABC transporter activates the integrin signaling pathway promoting axon regeneration. (2019)
  • Author(s): Pastuhov SI, Hisamoto N, tsuge A, Shimizu T, Hanafusa H, Matsumoto K.
  • Organizer: 22st International C. elegans Conference, Los Angeles, USA
  • Int'l Joint Research
• [Presentation] C. elegans TDP2 homolog negatively regulates axon regeneration by inducing SUMOylatiuon of an Ets transcription factor. (2019)
  • Author(s): Sakai Y, Hanafusa H, Li C, Shimizu T, Pastuhov SI, Hisamoto N, Matsumoto K.
  • Organizer: 22st International C. elegans Conference, Los Angeles, USA
  • Int'l Joint Research
• [Presentation] C. elegans Tensin promotes axon regeneration by connecting the Met-like SVH-2 and integrin signaling pathway. (2019)
  • Author(s): Shimizu T, Asai K, Sakai Y, Pastuhov SI, Hanafusa H, Matsumoto K, Hisamoto N.
  • Organizer: 22st International C. elegans Conference, Los Angeles, USA
  • Int'l Joint Research
• [Presentation] The C. elegans BRCA2-ALP/Enigma complex regulates axon regeneration via a Rho GTPase-MLC phosphorylation pathway. (2018)
  • Author(s): T. Shimizu
  • Organizer: 2018 Asia-Pacific Meeting, Seoul, Korea
  • Int'l Joint Research
• [Presentation] The role of serotonin in C. elegans axon regeneration. (2017)
  • Author(s): Hisamoto N
  • Organizer: International Workshop on NeuroScience, Nagoya, Japan
  • Int'l Joint Research / Invited
• [Presentation] N-glycosylation is required for axon regeneration in Caenorhabditis elegans through modification of discoidin domain receptor. (2017)
  • Author(s): Takeo M, Kato Y, Matsumoto K, K, Hisamoto N
  • Organizer: 21st International C. elegans Conference, Los Angeles, USA
  • Int'l Joint Research
• [Presentation] 線虫EnigmaホモログによるRhoキナーゼシグナルを介した神経軸索再生制御 (2017)
  • Author(s): 清水達太、松本邦弘、久本直毅
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] 線虫においてコンドロイチン硫酸は加齢依存的な神経軸索の再生能低下に関与する (2017)
  • Author(s): 竹生実希子、松本邦弘、久本直毅
  • Organizer: 2017年度生命科学系学会合同年次大会