Regulation of neuronal spine by ubiquitination

• Project/Area Number: 15K21769
• Research Category: Fund for the Promotion of Joint International Research (Home-Returning Researcher Development Research)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Foundation for Biomedical Research and Innovation at Kobe
• Principal Investigator: KAWABE Hiroshi 公益財団法人神戸医療産業都市推進機構, 上席研究員 (00582454)
• Project Period (FY): 2017 – 2019
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥57,200,000 (Direct Cost: ¥44,000,000、Indirect Cost: ¥13,200,000)
• Keywords: スパイン / ユビキチン化 / 超解像顕微鏡 / 超高解像度顕微鏡 / 細胞内情報伝達

Outline of Final Research Achievements

In the neuronal network, information is transferred between two neurons via synapses. Postsynapse is integrated in the dendritic spine. The size of spine is related to the number of neurotransmitter receptors on it and the regulation of spine morphology is of particular importance for the understanding of the pathology of psychiatric disorders. In our project, we studied the role of specific protein ubiquitination mediated by HECT type E3 ligases in the regulation of neuronal development including the spine formation.

Academic Significance and Societal Importance of the Research Achievements

本課題の研究で、これまで未知の部分が多かったユビキチン化による神経細胞発達の制御機構に関して、多くの知見が得られた。中でも知的障害を伴う発達障害であるKaufman症候群の原因遺伝子でE3ユビキチンリガーゼをコードするUbe3Bが、スパインの形成と形態を制御する機構を見出した。この成果は将来的に知的障害の原因の解明や治療に発展する可能性がある。

Research Products

• [Int'l Joint Research] Max Planck Institute of Experimental Medicine/Charité-Universitätsmedizin/Ulm University(ドイツ)
• [Int'l Joint Research] University of British Columbia/McGill University/The University of Western Ontario(カナダ)
• [Int'l Joint Research] Harvard Medical School/Stanford University/National Institutes of Health(アメリカ合衆国)
• [Int'l Joint Research] Fudan University(中国)
• [Int'l Joint Research] University of Basel(スイス)
• [Int'l Joint Research]
• [Int'l Joint Research] ベルリン・Charité医科大学/Max Planck Institute of Experimental Medicine/Max Planck Institute for Biophysical Chemistry（ドイツ）
• [Int'l Joint Research] ハーバード大学（米国）
• [Int'l Joint Research]
• [Int'l Joint Research] ベルリン・Charite医科大学/Max Planck Institute of Experimental Medicine/Max Planck Institute for Biophysical Chemistry(ドイツ)
• [Int'l Joint Research] ハーバード大学(米国)
• [Int'l Joint Research]
• [Journal Article] Optimizing Nervous System-Specific Gene Targeting with Cre Driver Lines: Prevalence of Germline Recombination and Influencing Factors (2020)
  • Author(s): Luo, L.、19名略、Sinclair, J. L.、Stogsdill, J. A.、Traunmuller, L.、Wang, J.、Wortel, J.、 You, W.、 Abumaria, N.、 Beier, K. T.、 Brose, N.、 Burgess, H. A.、 Cepko, C. L.、 Cloutier, J. F.、 Eroglu, C.、 Goebbels, S.、 Kaeser, P. S.、 Kay, J. N.、 Lu, W.、 Luo, L.、 Mandai, K.、15名略、Kawabe, H.、 Craig, A. M.
  • Journal Title: Neuron Volume: 106 Issue: 1 Pages: 37-65
  • DOI: 10.1016/j.neuron.2020.01.008
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The murine ortholog of Kaufman oculocerebrofacial syndrome protein Ube3b regulates synapse number by ubiquitinating Ppp3cc. (2020)
  • Author(s): Ambrozkiewicz MC*, Borisova E, Schwark M, Ripamonti S, Schaub T, Smorodchenko A, Weber AI, Rhee HJ, Altas B, Yilmaz R, Mueller S, Piepkorn L, Horan ST, Straussberg R, Zaqout S, Jahn O, Dere E, Rosario M, Boehm-Sturm P, Borck G, Willig K, Rhee JS, Tarabykin V, and Kawabe H. * *=Corresponding authors
  • Journal Title: Molecular Psychiatry Volume: 106 Issue: 6 Pages: 1980-1995
  • DOI: 10.1038/s41380-020-0714-8
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Polarity Acquisition in Cortical Neurons Is Driven by Synergistic Action of Sox9-Regulated Wwp1 and Wwp2 E3?Ubiquitin Ligases and Intronic miR-140 (2018)
  • Author(s): Ambrozkiewicz MC、Schwark M、Kishimoto-Suga M、Borisova E、Hori K、Salazar-L?zaro A、Rusanova A、Altas B、Piepkorn L、Bessa P、Schaub T、Zhang X、Rabe T、Ripamonti S、Ros?rio M、Akiyama H、Jahn O、Kobayashi T、Hoshino M、Tarabykin V、Kawabe H
  • Journal Title: Neuron Volume: 100 Issue: 5 Pages: 1097-1115
  • DOI: 10.1016/j.neuron.2018.10.008
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Molecular mechanisms of Streptococcus pneumoniae-targeted autophagy via pneumolysin, Golgi-resident Rab41, and Nedd4-1-mediated K63-linked ubiquitination (2018)
  • Author(s): Ogawa M, Matsuda R, Takada N, Tomokiyo M, Yamamoto S, Shizukusihi S, Yamaji T, Yoshikawa Y, Yoshida M, Tanida I, Koike M, Murai M, Morita H, Takeyama H, Ryo A, Guan JL, Yamamoto M, Inoue JI, Yanagawa T, Fukuda M, Kawabe H, Ohnishi M
  • Journal Title: Cellular Microbiology Volume: e12846 Issue: 8
  • DOI: 10.1111/cmi.12846
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] NEDD4 controls spermatogonial stem cell homeostasis and stress response by regulating messenger ribonucleoprotein complexes. (2017)
  • Author(s): Zhou Z, Kawabe H, Suzuki A, Shinmyozu K, Saga Y.
  • Journal Title: Nature Communication. Volume: 8 Issue: 1 Pages: 15662-15662
  • DOI: 10.1038/ncomms15662
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Deletion of Nedd4-2 results in progressive kidney disease in mice. (2017)
  • Author(s): Henshall, T. L., Manning, J. A., Alfassy, O. S., Goel, P., Boase, N. A., Kawabe, H., and Kumar, S.
  • Journal Title: Cell Death and Differentiation Volume: 24 Issue: 12 Pages: 2150-2160
  • DOI: 10.1038/cdd.2017.137
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The E3 ubiquitin ligase NEDD4 enhances killing of membrane-perturbing intracellular bacteria by promoting autophagy. (2017)
  • Author(s): Pei, G., Buijze, H., Liu, H., Moura-Alves, P., Goosmann, C., Brinkmann, V., Kawabe, H., Dorhoi, A., and Kaufmann, S.H.E.
  • Journal Title: Autophagy Volume: 13 Issue: 12 Pages: 2041-2055
  • DOI: 10.1080/15548627.2017.1376160
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 神経細胞発達におけるWWP E3ユビキチンリガーゼとmiR140の役割 (2017)
  • Author(s): 川辺 浩志
  • Organizer: 第40回日本神経科学大会