Regulatory mechanism of AMPA receptor dynamics by phospholipase A_2

• Project/Area Number: 22700405
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: 財団法人東京都医学総合研究所 (2011); Tokyo Metropolitan Organization for Medical Research (2010)
• Principal Investigator: HIRABAYASHI Tetsuya 財団法人東京都医学総合研究所, 生体分子先端研究分野, 主席研究員 (90345025)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 神経可塑性 / アラキドン酸 / 蛍光イメージング / 脂質 / 酵素 / 神経科学

Research Abstract

Trafficking of AMPA-type glutamate receptor subunit GluR2 in Purkinje neurons is a key mechanism to modulate long-term depression(LTD) in the cerebellum, which contributes to certain forms of motor learning and coordination. We have shown that full activation of cytosolic phospholipase A_2αand consequent liberation of arachidonic acid from membrane phospholipids are required for the prolonged decrease in the synaptic-surface expression of GluR2.To elucidate the regulatory mechanism of GluR2 dynamics by phospholipase A_2 and arachidonic acid, we attempted spatial and temporal control of local free arachidonic acid liberation using photolysis of caged compounds, visualization of internalized GluR2 movement, and comparative analysis of phospholipid composition.

Research Products

• [Journal Article] PGD_2 induces eotaxin-3 via PPARγ from sebocytes : a possible pathogenesis of eosinophilic pustular folliculitis (2012)
  • Author(s): Nakahigashi, K., et al
  • Journal Title: J.Allergy Clin.Immunol. Volume: 129 Issue: 2 Pages: 536-543
  • DOI: 10.1016/j.jaci.2011.11.034
  • Peer Reviewed
• [Journal Article] Recent progress in phospholipase A_2 research : from cells to animals to humans. (2011)
  • Author(s): Murakami M, Taketomi Y, Miki Y, Sato H, Hirabayashi T, Yamamoto K.
  • Journal Title: Prog Lipid Res Volume: 50 Pages: 152-92
  • Peer Reviewed
• [Journal Article] Analysis of two major intracellular phospholipase A2s in mast cells reveals crucial contribution of cPLA2alpha, not iPLA2beta, to lipid mobilization in proximal mast cells and distal fibroblasts. (2011)
  • Author(s): Ueno, N., Taketomi, Y., Yamamoto, K., Hirabayashi, T., Kamei, D., Kita, Y., Shimizu, T., Shinzawa, K., Tsujimoto, Y., Ikeda, K., Taguchi, R., Murakami, M.
  • Journal Title: J. Biol. Chem. Volume: 186 Issue: 43 Pages: 37249-37263
  • DOI: 10.1074/jbc.m111.290312
  • Peer Reviewed
• [Journal Article] Recent progress in phospholipase A_2 research : from cells to animals to humans (2011)
  • Author(s): Murakami, M., Taketomi, Y., Miki, Y., Sato, H., Hirabayashi, T., and Yamamoto, K.
  • Journal Title: Prog. Lipid Res Volume: 50 Issue: 2 Pages: 152-192
  • DOI: 10.1016/j.plipres.2010.12.001
  • Peer Reviewed
• [Presentation] 脂肪滴形成における脂質代謝酵素PNPLA5の機能解析 (2011)
  • Author(s): 平林哲也、横山浩平、堀山正雄、島村透、片桐千仭、村上誠
  • Organizer: 日本生化学会大会第84回年会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-24
• [Presentation] Novel lipid-metabolizing enzyme induced in sebocytes (2010)
  • Author(s): 平林哲也
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2010-12-07
• [Presentation] 皮膚に発現する新規脂質代謝酵素の機能解析 (2010)
  • Author(s): 平林哲也
  • Organizer: 第52回日本脂質生化学会
  • Place of Presentation: 群馬県渋川市
  • Year and Date: 2010-06-14
• [Book] 「ホスホリパーゼA_2の生理的・病理的役割」実験医学 (2010)
  • Author(s): 村上誠、佐藤弘泰、平林哲也、山本圭、武富芳隆