Regulation of neuronal cell size control in normal and disease condition

• Project/Area Number: 25430064
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Niigata University
• Principal Investigator: Takei Nobuyuki 新潟大学, 脳研究所, 准教授 (70221372)
• Co-Investigator(Kenkyū-buntansha): KAKITA Akiyoshi 新潟大学, 脳研究所, 教授 (80281012)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: mTOR / 細胞サイズ / 神経細胞 / 蛋白合成 / BDNF / AMPK / 脂質合成 / 限局性皮質形成異常 / FCD

Outline of Final Research Achievements

We have analyzed the signaling transduction pathways of mammalian target of rapamycin (mTOR), that is a key enzyme of cell size control. We identified several molecules that regulate the activity of mTOR in neurons. We revealed that activation of mTOR leads to the upregulation of protein and lipid synthesis and its link to the cell size in CNS neurons. In disease study, we found novel somatic mutations of MTOR in Forcal Cortical Dysplasia IIb (FCDIIb) brain and confirm that these mutations make mTOR hyperactive.

Research Products

• [Int'l Joint Research] Dept. of Med.Biochem. & Biol./Dartmouth Medical School(米国)
• [Int'l Joint Research] Dept. of Mol. Biol./Massachusetts General Hospital(米国)
• [Journal Article] Somatic Mutations in the MTOR gene cause focal cortical dysplasia type IIb (2015)
  • Author(s): Nakashima M, Saitsu H, Takei N, Tohyama J, Kato M, Kitaura H, Shiina M, Shirozu H, Masuda H, Watanabe K, Ohba C, Tsurusaki Y, Miyake N, Zheng Y, Sato T, Takebayashi H, Ogata K, Kameyama S, Kakita A, Matsumoto N
  • Journal Title: Ann. Neurol. Volume: 78 Issue: 3 Pages: 375-386
  • DOI: 10.1002/ana.24444
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A possible link between BDNF and mTOR in control of food intake. (2014)
  • Author(s): Takei N, Furukawa K, Hanyu O, Sone H, NawaH
  • Journal Title: Front. Psychol Volume: 5
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] mTOR signaling and its roles in normal and abnormal brain development. (2014)
  • Author(s): Takei N and Nawa H.
  • Journal Title: Front Mol Neurosci. Volume: 7 Pages: 28-28
  • DOI: 10.3389/fnmol.2014.00028
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Neuropathologic implication of peripheral neuregulin-1 and EGF signals in dopaminergic dysfunction and behavioral deficits relevant to schizophrenia: their target cells and time window. (2014)
  • Author(s): Nawa H, Sotoyama H, Iwakura Y, Takei N, Namba H.
  • Journal Title: Biomed Res Int. Volume: n/a Pages: 697935-697935
  • DOI: 10.1155/2014/697935
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] AMP-activated protein kinase counteracts brain-derived neurotrophic factor-induced mammalian target of rapamycin complex 1 signaling in neurons. (2013)
  • Author(s): Ishizuka Y, Kakiya N, Witters LA, Oshiro N, Shirao T, Nawa H, Takei N.
  • Journal Title: J Neurochem. Volume: 127 Issue: 1 Pages: 66-77
  • DOI: 10.1111/jnc.12362
  • Peer Reviewed
• [Journal Article] ErbB2 dephosphorylation and anti-proliferative effects of neuregulin-1 in ErbB2-overexpressing cell lines; re-evaluation of their low-affinity interaction. (2013)
  • Author(s): Wang, R., Iwakura, Y., Araki, K., Keino-Masu, K., Masu, M., Wang, X., Takei, N., Higashiyama, S. and Nawa, H.
  • Journal Title: Scientific reports Volume: 3 Issue: 1 Pages: 1402-1402
  • DOI: 10.1038/srep01402
  • Peer Reviewed
• [Presentation] mTORシグナル系と脳形成異常 (2015)
  • Author(s): 武井延之
  • Organizer: BMB2015
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] EGF downregulates presynaptic maturation and suppresses synapse formation in vitro and in vivo (2015)
  • Author(s): Takei N, Yokomaku D, Ushiki T, Nawa H
  • Organizer: 25th ISN Meeting
  • Place of Presentation: Cairns, Australia
  • Year and Date: 2015-08-24
  • Int'l Joint Research
• [Presentation] mTOR mediates neuronal maturation and cell size control. (2014)
  • Author(s): Nobuyuki Takei
  • Organizer: ISN satellite symposium on “ Key molecules for neuronal maturation”
  • Place of Presentation: Yayoi Auditorium, The University of Tokyo, Tokyo
  • Year and Date: 2014-09-23
  • Invited
• [Presentation] Atomic Force Microscopic Imaging of Growth Cones from Rat Dorsal Root Ganglion Neurons (2014)
  • Author(s): Osamu Hoshi, Yuichiro Cho, Nobuyuki Takei
  • Organizer: ISN Special Conference
  • Place of Presentation: Yayoi Auditorium, The University of Tokyo, Tokyo
  • Year and Date: 2014-09-20 – 2014-09-22
• [Presentation] 冬眠時シマリス脳におけるAMPK を介した翻訳抑制機構 (2013)
  • Author(s): 山田 新太郎,近藤 宣昭,那波 宏之,関島 恒夫,武井 延之
  • Organizer: ３６回日本分子生物学会
  • Place of Presentation: 神戸国際会議場
• [Book] サイトカイン・増殖因子キーワード事典 (2015)
  • Author(s): 武井延之（分担） （宮園浩平、秋山徹、宮島篤、宮澤恵二編集）
  • Total Pages: 420
  • Publisher: 羊土社
• [Book] 脳神経科学イラストレイテッド第三版 (2013)
  • Author(s): 武井延之
  • Total Pages: 8
  • Publisher: 羊土社
• [Remarks] 新潟大学脳研究所
  • URL: http://www.bri.niigata-u.ac.jp/