Study on the role of extracellular deubiquitinating enzymes

• Project/Area Number: 23650199
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: WADA Keiji 独立行政法人国立精神・神経医療研究センター, 神経研究所疾病研究第四部, 部長 (70250222)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 蛋白質 / 脳神経疾患 / 神経科学 / 生理活性 / 細胞 / 組織 / 脱ユビキチン化酵素 / 神経細胞 / ネットワーク / 生体情報 / 分泌 / パーキンソン病 / モデル動物 / 脳科学

Research Abstract

We aimed to elucidate the biological role of extracellular UCH-L1. To achieve this purpose, we used cultured cells and studied whether the protein was secreted or not into the media. We observed that UCH-L1 was secreted into the media via a unconventional pathway. Interestingly, exosome contained UCH-L1. I93M UCH-L1 mutant was less secreted compared with wild type of UCH-L1. Then we studied a possible interaction of UCH-L1 with other disease-related proteins in the secretory event. We found that the secretion of UCH-L1 was modified by the presence of mutated alpha-synuclein and huntingtin. These results suggest that secretion of UCH-L1 into extracellular space might be related to the pathophysiological conditions of neurodegenerative disorders.

Research Products

• [Journal Article] Ubiquitin C-terminal hydrolase L1 (UCH-L1) act as a novel potentiator of cyclin-dependent kinases to enhance cell proliferation, independent of its hydrolase activity (2013)
  • Author(s): Kabuta, T., Mitsui, T., Takahashi, M., Fujiwara, Y., Kabuta, C., Konya, C., Tsuchiya, Y., Hatanaka, Y., Uchida, K., Hohjoh, H., Wada, K
  • Journal Title: J. Biol. Chem Volume: 288 Issue: 18 Pages: 12615-12626
  • DOI: 10.1074/jbc.m112.435701
  • Peer Reviewed
• [Journal Article] Sulfatide accumulation in the dystrophic terminals of gracile axonal dystrophy mice: lipid analysis using matrix-assisted laser desorption/ionization imaging mass spectrometry (2013)
  • Author(s): Onishi, K., Tasumi, Y., Wada, K., Yang, H.J., Sugiura, Y., Setou, M., Yoshikawa, H
  • Journal Title: Med. Mol. Morphol Volume: (Epub ahead of print)
  • NAID: 10031203183
  • Peer Reviewed
• [Journal Article] Ubiquitin C-terminal hydrolase L1 (UCH-L1) act as a novel potentiator of cyclin-dependent kinases to enhance cell proliferation, independent of its hydrolase activity. (2013)
  • Author(s): Kabuta, T.
  • Journal Title: Journal of Biological Chemistry Volume: 未定
  • Peer Reviewed
• [Journal Article] Control of BACE1 and APP processing by ubiquitin carboxyl-terminal hydrolase L1 in Alzheimer's Disease Pathogenesis (2012)
  • Author(s): Zhang, M., et al
  • Journal Title: J Neurochem Volume: 120 Issue: 6 Pages: 1129-1138
  • DOI: 10.1111/j.1471-4159.2011.07644.x
  • Peer Reviewed
• [Journal Article] Selective Neuroprotective Effects of the S18Y Polymorphic Variant of UCH-L1 in the dopaminergic system (2012)
  • Author(s): Xilouri, M., et al
  • Journal Title: Hum Mol Genet Volume: 21 Issue: 4 Pages: 874-879
  • DOI: 10.1093/hmg/ddr521
  • Peer Reviewed
• [Journal Article] Uchl1 is required for β-cell survival and function in prediabetic lipotoxic conditions (2012)
  • Author(s): Chu, K.Y., et al
  • Journal Title: Diabetologia Volume: 55 Issue: 1 Pages: 128-140
  • DOI: 10.1007/s00125-011-2323-1
  • Peer Reviewed
• [Journal Article] Parkinson's disease-associated mutations in alpha-synuclein and UCH-L1 inhibit the unconventional secretion of UCH-L1 (2011)
  • Author(s): Konya, C.
  • Journal Title: Neurochem Int Volume: 59 Issue: 2 Pages: 251-258
  • DOI: 10.1016/j.neuint.2011.05.012
  • Peer Reviewed
• [Presentation] 神経変性疾患の予防をめざして:脳―臓器間ネットワークからの解析 (2012)
  • Author(s): 和田圭司
  • Organizer: 大阪大学蛋白質研究所セミナー神経疾患の克服に向けて
  • Place of Presentation: 大阪
• [Presentation] 神経変性疾患の予防をめざして：脳―臓器間ネットワークからの解析 (2012)
  • Author(s): 和田圭司
  • Organizer: 大阪大学蛋白質研究所セミナー(招待講演)
  • Place of Presentation: 大阪大学蛋白質研究所（大阪）
• [Presentation] 中枢神経系‐神経症状のようなものを見つけたときにどうするか:論文化への道標‐ (2011)
  • Author(s): 和田圭司
  • Organizer: 第58回日本実験動物学会総会
  • Place of Presentation: 東京
• [Presentation] gadmouse 延髄薄束核における神経軸索内蓄積物の検討 (2011)
  • Author(s): 大西沙代子, 芳川浩男, 辰己吉記, 杉 浦悠毅, 梁腎正, 和田圭司, 瀬藤光 利
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 名古屋
• [Presentation] 中枢神経系－神経症状のようなものを見つけたときにどうするか：論文化への道標－ (2011)
  • Author(s): 和田圭司
  • Organizer: 第58回日本実験動物学会総会(招待講演)
  • Place of Presentation: タワーホール船堀（東京）
• [Remarks]
  • URL: http://www.ncnp.go.jp/nin/guide/r4/index.html
• [Remarks]
  • URL: http://www.ncnp.go.jp/nin/guide/r4/index.html