Determination of the receptor type protein tyrosine phosphatase of to the oligodendrocyte differentiation

• Project/Area Number: 26830050
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: National Institute for Basic Biology
• Principal Investigator: KUBOYAMA Kazuya 基礎生物学研究所, 統合神経生物学研究部門, 特別協力研究員 (20619671)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 神経科学 / タンパク質チロシンリン酸化シグナル / チロシンホスファターゼ / オリゴデンドロサイト / 脱髄疾患 / グリア細胞 / 脳・神経 / プロテインチロシンホスファターゼ / チロシンリン酸化

Outline of Final Research Achievements

The purpose of this study was to determine the regulatory mechanism of protein tyrosine phosphatase receptor type Z (PTPRZ), which inhibits oligodendrocyte differentiation and myelination/remyelination. Here we revealed that the expression of pleiotrophin is transiently upregulated in damaged neurons after demyelination. Pleiotrophin may be released from demyelinated axons and bind to PTPRZ at the cell surface of oligodendrocyte precursor cells, thereby releases the block of differentiation into oligodendrocyte, so the remyelination of neighboring axon is initiated.

Research Products

• [Journal Article] Small-molecule inhibition of PTPRZ reduces tumor growth in a rat model of glioblastoma. (2016)
  • Author(s): Fujikawa A, Nagahira A, Sugawara H, Ishii K, Imajo S, Matsumoto M, Kuboyama K, Suzuki R, Tanga N, Noda M, Uchiyama S, Tomoo T, Ogata A, Masumura M, Noda M.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 20473-20473
  • DOI: 10.1038/srep20473
  • Peer Reviewed / Open Access
• [Journal Article] Inactivation of protein tyrosine phosphatase receptor type Z by pleiotrophin promotes remyelination through activation of differentiation of oligodendrocyte precursor cells (2015)
  • Author(s): Kuboyama, K., Fujikawa, A., Suzuki, R., and Noda, M
  • Journal Title: J. Neurosci. Volume: 35 Issue: 35 Pages: 12162-12171
  • DOI: 10.1523/jneurosci.2127-15.2015
  • Peer Reviewed
• [Journal Article] Channel properties of Nax expressed in neurons. (2015)
  • Author(s): Matsumoto M, Hiyama TY, Kuboyama K, Suzuki R, Fujikawa A, Noda M.
  • Journal Title: PLoS One Volume: 10 Issue: 5 Pages: e0126109-e0126109
  • DOI: 10.1371/journal.pone.0126109
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Specific dephosphorylation at tyr-554 of git1 by ptprz promotes its association with paxillin and hic-5. (2015)
  • Author(s): Fujikawa A, Matsumoto M, Kuboyama K, Suzuki R, Noda M.
  • Journal Title: PLoS One Volume: 10 Issue: 3 Pages: 1-20
  • DOI: 10.1371/journal.pone.0119361
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Loss of Function Mutation in APC2 Causes Sotos Syndrome Features. (2015)
  • Author(s): Almuriekhi, M., Shintani, T., Fahiminiya, S., Fujikawa, A., Kuboyama, K., Takeuchi, Y., Nawaz, Z., Nadaf, J., Kamel, H., Kitam, A.K., Samiha, Z., Mahmoud, L., Ben-Omran, T., Majewski, J. & Noda, M.
  • Journal Title: Cell Reports Volume: 10 Issue: 9 Pages: 1585-1598
  • DOI: 10.1016/j.celrep.2015.02.011
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] pleiotrophin-PTPRZシグナルによる オリゴデンドロサイトの分化と再ミエリン化の制御機構 (2016)
  • Author(s): 久保山和哉, 藤川顕寛, 鈴木亮子, 野田昌晴
  • Organizer: 第7回 日本プロテインホスファターゼ研究会学術集会
  • Place of Presentation: 自然科学研究機構（愛知県岡崎市）
  • Year and Date: 2016-01-29
• [Presentation] Role of Pleiotrophin-PTPRZ Signaling in Oligodendrocyte Differentiation and Remyelination. (2015)
  • Author(s): 久保山和哉, 藤川顕寛, 鈴木亮子, 野田昌晴
  • Organizer: 第88回 日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] Loss-of-Function Mutation in APC2 Causes Sotos Syndrome Features. (2015)
  • Author(s): 新谷隆史, Fahiminiya S, Almuriekhi M, 藤川顕寛, 久保山和哉, 竹内靖, Nawaz Z, Nadaf J, Kamel H, Kitam KA, Samiha Z, Mahmoud L, Ben-Omran T, Majewski J, 野田昌晴
  • Organizer: 第38回 日本神経科学大会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-07-28
• [Presentation] Specific dephosphorylation at Tyr-554 of Git1 by Ptprz promotes its association with paxillin and Hic-5. (2014)
  • Author(s): Fujikawa A, Matsumoto M, Kuboyama K, Suzuki R, Noda M.
  • Organizer: 第11回 プロテインホスファターゼ国際カンファレンス
  • Place of Presentation: 東北大学医学部 艮陵会館 (宮城県 仙台市)
  • Year and Date: 2014-11-12 – 2014-11-14
• [Remarks] 髄鞘再生に関わる分子機構の解明 ～神経回路の絶縁シートが回復する仕組み～
  • URL: http://www.nibb.ac.jp/press/2015/09/03.html
• [Remarks] オリゴデンドロサイト系譜OL1細胞（YouTube動画）
  • URL: https://www.youtube.com/watch?v=nqxigfwvJ4I
• [Remarks] マウス脳のX線CT（YouTube動画）
  • URL: https://www.youtube.com/watch?v=O_ReIADiR0I