Remodeling of nuclear transport system in terminal differentiation of cortical neurons

• Project/Area Number: 26830047
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Osaka University
• Principal Investigator: Fujiwara Kazushiro 大阪大学, たんぱく質研究所, 助教 (80638495)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• 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: ニューロン / 分化 / RanGAP1 / SUMO / RanGAP / ニューロン分化 / 核輸送 / Cdc6 / 最終分化 / 核-細胞質間輸送 / 神経分化 / SUMO化

Outline of Final Research Achievements

Neuronal terminal differentiation rapidly promoted desumoylation of RanGAP1 and reduced the levels of nuclear pore-associated RanGAP1. Downregulation of RanGAP1 expression impeded the nuclear import of nucleocytoplasmic shuttling proteins including the DNA replication initiation factor Cdc6 and accelerated cell cycle exit of neuronal progenitors. These results suggest that remodeling of the RanGAP1-mediated nuclear transport system plays a key role in cell cycle exit for terminal differentiation of cortical neurons.

Research Products

• [Journal Article] Terminal differentiation of cortical neurons rapidly remodels RanGAP-mediated nuclear transport system. (2016)
  • Author(s): Fujiwara K, Hasegawa K, Oka M, Yoneda Y, Yoshikawa K.
  • Journal Title: Genes Cells Volume: 21 Issue: 11 Pages: 1176-1194
  • DOI: 10.1111/gtc.12434
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Promotion of mitochondrial biogenesis by necdin protects neurons against mitochondrial insults. (2016)
  • Author(s): Hasegawa, K., Yasuda, T., Shiraishi, C., Fujiwara, K., Przedborski, S., Mochizuki, H., Yoshikawa, K.
  • Journal Title: Nature Communications Volume: 7 Issue: 1 Pages: 10943-10943
  • DOI: 10.1038/ncomms10943
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Necdin controls EGFR signaling linked to astrocyte differentiation in primary cortical progenitor cells. (2016)
  • Author(s): Fujimoto, I., Hasegawa, K., Fujiwara, K., Yamada, M., Yoshikawa, K.
  • Journal Title: Cellular Signalling Volume: 28 Issue: 2 Pages: 94-107
  • DOI: 10.1016/j.cellsig.2015.11.016
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Necdin promotes ubiquitin-dependent degradation of PIAS1 SUMO E3 ligase (2014)
  • Author(s): Gur, I., Fujiwara, K., Hasegawa, K., Yoshikawa, K.
  • Journal Title: PLoS One Volume: 9 Issue: 6 Pages: e99503-e99503
  • DOI: 10.1371/journal.pone.0099503
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] ニューロン分化におけるNecdinによるRanGAP1のSUMO化制御 (2015)
  • Author(s): 藤原 一志郎、長谷川 孝一、吉川 和明
  • 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: 2015-12-03
• [Presentation] Necdin promotes mitochondrial biogenesis to prevent neurodegeneration in experimental Parkinson’s disease. (2015)
  • Author(s): Hasegawa, K., Yasuda, T., Shiraishi, C., Fujiwara, K., Mochizuki, K., Yoshikawa, K.
  • Organizer: Neuroscience 2015
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-10-21
  • Int'l Joint Research
• [Presentation] Necdin downregulates EGFR signaling in cortical neural precursor cells to suppress gliogenesis. (2015)
  • Author(s): Fujimoto, I., Hasegawa, K., Fujiwara, K., Yoshikawa, K.
  • Organizer: Neuroscience 2015
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-10-20
  • Int'l Joint Research
• [Presentation] Necdin regulates RanGAP1 sumoylation during neuronal differentiation (2014)
  • Author(s): Fujiwara K, Hasegawa K, Yoshikawa K.
  • Organizer: Neuroscience 2014
  • Place of Presentation: Walter E. Washington Convention Center, Washington, DC
  • Year and Date: 2014-11-15
• [Presentation] Necdinによる上皮成長因子受容体シグナルの制御機構 (2014)
  • Author(s): 藤本 泉, 長谷川 孝一, 藤原 一志郎, 吉川 和明
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館、京都
  • Year and Date: 2014-10-18