Negative regulation of axonal myelination

• Project/Area Number: 25290028
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Yamauchi Junji 国立研究開発法人国立成育医療研究センター, 薬剤治療研究部, 室長 (20335483)
• Research Collaborator: KAWAHARA KAZUKO 国立研究開発法人国立成育医療研究センター, 薬剤治療研究部, 研究補助員
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2016: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
• Keywords: ミエリン形成 / 脱ミエリン現象 / 抑制シグナル / 促進シグナル / サイトヘジン / Arf6 / シグナル伝達分子 / 脱ミエリン疾患 / ミエリン / 髄鞘 / サイトヘジン1 / サイトヘジン2 / ACAP2 / 髄鞘髄鞘 / 脱髄 / 創薬 / シグナル伝達 / 創薬標的 / ミエリン形成促進 / ミエリン形成抑制 / 低分子量GTP結合蛋白質 / 増殖因子受容体 / 障害後再生 / 再生プログラム / 発生プログラム / 髄鞘発生 / 髄鞘形成 / 脱髄改善 / 交換因子 / GTPアーゼ活性化蛋白質 / Arfファミリー / Rhoファミリー / ミエリン発生 / ミエリン形成の抑制 / ミエリン形成の促進 / シグナル伝達因子 / 創薬標的分子 / 創薬標的候補分子 / 治療標的候補分子

Outline of Final Research Achievements

It is believed that myelination in mammals is regulated by positive and negative signaling molecules; however, it remains to be understood what and how molecule controls myelination. Here we investigate inhibitory signaling for myelination in the peripheral nervous system. We clarify that the molecular pathway controlled by cytohesin regulates myelination. We also find that this pathway is composed of two reciprocal signaling pathways. Further studies allow us not only to understand the detailed mechanim of myelination but also to identify a potential therapeutic target for dismyelination desieases.

Research Products

• [Journal Article] Yuki Miyamoto, Tomohiro Torii, Akito Tanoue, and Junji Yamauchi* (2016) VCAM1 acts in parallel with CD69 and is required for the initiation of oligodendrocyte myelination. (2016)
  • Author(s): Yuki Miyamoto, Tomohiro Torii, Akito Tanoue, and Junji Yamauchi
  • Journal Title: Nat. Commun. Volume: 7 Pages: 13478-13478
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Data supporting Arf6 regulation of Schwann cell differentiation and myelination (2016)
  • Author(s): Tomohiro Torii, Yuki Miyamoto, Masahiro Yamamoto, Katsuya Ohbuchi, Hideki Tsumura, Kazuko Kawahara, Akito Tanoue, Hiroyuki Sakagami, and Junji Yamauchi
  • Journal Title: Data Brief Volume: 5 Pages: 388-395
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Arf6 guanine-nucleotide exchange factor cytohesin-2 regulates myelination in nerve (2016)
  • Author(s): Tomohiro Torii, Nobuhiko Ohno, Yuki Miyamoto, Kazuko Kawahara, Yurika Saitoh, Kazuaki Nakamura, Shou Takashima, Hiroyuki Sakagami, Akito Tanoue, and Junji Yamauchi
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 460 Pages: 819-825
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Involvement of the Tyro3 receptor and its intracellular partner Fyn signaling in Schwann cell myelination. (2015)
  • Author(s): Yuki Miyamoto, Tomohiro Torii, Shuji Takada, Nobuhiko Ohno, Yurika Saitoh, Kazuaki Nakamura, Akihito Ito, Toru Ogata, Nobuo Terada, Akito Tanoue, and Junji Yamauchi
  • Journal Title: Mol. Biol. Cell Volume: 26 Issue: 19 Pages: 3489-3503
  • DOI: 10.1091/mbc.e14-05-1020
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Arf6 mediates Schwann cell differentiation and myelination. (2015)
  • Author(s): Tomohiro Torii, Yuki Miyamoto, Masahiro Yamamoto, Katsuya Ohbuchi, Hideki Tsumura, Kazuo Kawahara, Akito Tanoue, Hiroyuki Sakagami, and Jyunji Yamauchi
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 465 Issue: 3 Pages: 450-457
  • DOI: 10.1016/j.bbrc.2015.08.038
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hypomyelinating leukodystrophy-associated missence mutation in HSPD1 blunts mitochondrial dynamics. (2015)
  • Author(s): Yuki Miyamoto, Takahiro Eguchi, Kazuo Kawahara, Nanami Hasegawa, Kazuaki Nakamura, Megumi Funakoshi-Tago, Akito Tanoue, Hiroomi Tamura, and Junji Yamauchi
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 462 Issue: 3 Pages: 275-281
  • DOI: 10.1016/j.bbrc.2015.04.132
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Rab35, acting through ACAP2 switching off Arf6, negatively regulates oligodendrocyte differentiation and myelination (2014)
  • Author(s): Miyamoto Y, Yamamori N, Torii T, Tanoue A, Yamauchi J
  • Journal Title: Mol. Biol. Cell Volume: 25 Issue: 9 Pages: 1532-1542
  • DOI: 10.1091/mbc.e13-10-0600
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Arf6 guanine nucleotide exchange factor cytohesin-2 binds to CCDC120 and is transported along neurites to mediate neurite growth (2014)
  • Author(s): Torii T, Miyamoto Y, Tago K, Sango K, Nakamura K, Sanbe A, Tanoue A, Yamauchi J
  • Journal Title: J. Biol. Chem. Volume: 289 Pages: 33887-33903
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Akt and PP2A reciprocally regulate the guanine nucleotide exchange factor Dock6 to control axon growth of sensory neurons. (2013)
  • Author(s): Yuki Miyamoto, Tomohiro Torii, Natsuki Yamamori, Toru Ogata, and Akito Tanoue, and Junji Yamauchi
  • Journal Title: Science Signaling (Science sister journal) Volume: 6 Issue: 265
  • DOI: 10.1126/scisignal.2003661
  • Peer Reviewed
• [Presentation] Tyro3受容体とFynキナーゼは、ミエリン形成を司る新しいシグナル複合体を形成する (2015)
  • Author(s): 宮本 幸、山内淳司
  • Organizer: 日本分子生物学会・日本生化学会合同年会（ワークショップ）
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] Disease-associated modification of hereditary demyelinating disorder-related protein dynamics (2015)
  • Author(s): 宮本 幸、山内淳司
  • Organizer: 日本神経化学会大会（シンポジウム）
  • Place of Presentation: 大宮
  • Year and Date: 2015-09-01
• [Presentation] Derivation of oligodendrocytes from human iPS cells and monkey ES cells maintained in a single-cell and feeder-free culture (2015)
  • Author(s): 山下智子、土井綾乃、小林桜子、小野貴史、鈴木 豊、荒木利博、青木久範、佐藤直也、宮本 幸、山内淳司、板東良雄、吉田成孝
  • Organizer: 日本神経科学会大会（ミニシンポジウム）
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-01
• [Presentation] ErbB3 is required for Schwann cell precursor migration (2015)
  • Author(s): 宮本 幸、山内淳司
  • Organizer: 日本神経科学会大会（ミニシンポジウム）
  • Place of Presentation: 神戸
  • Year and Date: 2015-07-01
• [Presentation] FynキナーゼとArf6交換因子cytohesin-1による新規のミエリン形成メカニズム (2013)
  • Author(s): 山内淳司
  • Organizer: 日本生化学会（シンポジウム）
  • Place of Presentation: 横浜
• [Remarks] 薬剤治療研究部
  • URL: http://nrichd.ncchd.go.jp/pharmac/
• [Remarks] 国立成育医療研究センター研究所HP
  • URL: http://www.ncchd.go.jp/research/nch/pharmac/staff02.html
• [Remarks] 国立成育医療研究センター研究所薬剤治療研究部HP
  • URL: http://nrichd.ncchd.go.jp/pharmac/
• [Remarks] 独立行政法人国立成育医療研究センター研究所薬剤治療研究部 HP
  • URL: http://nrichd.ncchd.go.jp/pharmac/