Information processing by the interaction of the ATP-sensors and mechano-sensors

2010 Fiscal Year Final Research Report

• Project Area: Molecular interaction and modal shift of cellular sensors
• Project/Area Number: 18077011
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: University of Yamanashi
• Principal Investigator: KOIZUMI Schuichi University of Yamanashi, 大学院・医学工学総合研究部, 教授 (10280752)
• Co-Investigator(Kenkyū-buntansha): FUJISHITA Kayoko 山梨大学, 大学院・医学工学総合研究部, 助教 (10443102) ; SHIBATA Keisuke 山梨大学, 大学院・医学工学総合研究部, 助教 (50580411) ; OKUBO Satoko 国立医薬品食品衛生研究所, 研究員 (20274954)
• Project Period (FY): 2006 – 2010
• Keywords: ミクログリア / 貪食 / アストロサイト / 神経細胞傷害 / ATP / UDP / ATPセンサー / モーダルシフト

Research Abstract

Microglia sense ATP leaked from damaged neurons by the ATP-sensor P2Y12, and migrate toward the injured site. If they meet UDP, eat-me signal, there, microglia start to phagocytose the damaged cells or debris to remove them from the brain. The UDP sensor is P2Y6. Microglia change their mode from migration to phagocytosis (modal-shift), which was associated with down- and up-regulation of P2Y12 and P2Y6, respectively. By such a modal-shift, microglia maintain the homeostasis of the CNS.

Research Products

• [Journal Article] Synchronized Ca^2+ oscillations in astrocytes. (2010)
  • Author(s): Koizumi, S.
  • Journal Title: FEBS J. 277 Pages: 286-292
• [Journal Article] The TRPV4 cation channel mediates stretch-evoked Ca^2+ influx and ATP release in primary urothelial cell cultures. (2009)
  • Author(s): Mochizuki, T., Tokabe, T., Araki, I., Fujishita, K., Shibasaki, K., Uchida, K., Naruse, K., Koizumi, S., Takeda, M.and Tominaga, M.
  • Journal Title: J.Biol.Chem. 284 Pages: 21257-21264
• [Journal Article] Grape seed extract (GSE) acting on astrocytes, reveals its neuronal protection against oxidative stress via interleukin-6-mediated mechanisms. (2009)
  • Author(s): Fujishita, K., Ozawa, T., Shibata, K., Tanabe, S., Sato, Y., Hisamoto, M., Okuda, T., Koizumi, S.
  • Journal Title: Cell Mol Neurobiol. 29 Pages: 1121-1129
• [Journal Article] Direct observation of ATP-induced conformational changes in single P2X_4 receptors. (2009)
  • Author(s): Shinozaki, Y., Sumitomo, K., Tsuda, M., Koizumi, S., Inoue, K.and Torimitsu, K.
  • Journal Title: PLoS Biology 7 Pages: 103
• [Journal Article] Activation of P2Y_1 receptors in astrocytes interferes the H_2O_2-evoked death promoting signaling cascades. (2009)
  • Author(s): Shinozaki, T., Koizumi, S., Ohno, T., Nagao, T.and Inoue, K.
  • Journal Title: Glia 54(6) Pages: 606-618
• [Journal Article] Retinoic acids acting through retinoid receptors protect hippocampal neurons from oxygen-glucose deprivation-mediated cell death by inhibition of c-Jun-N-terminal kinase and p38 mitogen-activated protein kinase. (2007)
  • Author(s): Shinozaki, Y., Sato, Y., Koizumi, S., Ohno, Y., Nagao, T.and Inoue, K.
  • Journal Title: Neurosci. 147 Pages: 153-163
• [Journal Article] UDP acting at P2Y_6 receptors is a novel mediator of microglial phagocytosis. (2007)
  • Author(s): Koizumi, S., Shigemoto-Mogami, Y., Nasu-Tada, K., Shinozaki, Y., Ohsawa, K., Tsuda, M., Joshi, B.V., Jacobson, K.A., Kohsaka, S., Inoue, K.
  • Journal Title: Nature 446 Pages: 1091-1095
• [Presentation] Mechanisms underlying upregulation of microglial P2Y6 receptors. (2010)
  • Author(s): Koizumi, S., Fujishita, K., Nakao, A.
  • Organizer: Society for Neuroscience Meeting
  • Place of Presentation: San Diego, USA.
  • Year and Date: 20101014-20101017
• [Presentation] Contribution of astrocytes to the "French paradox" in the CNS. (2009)
  • Author(s): Koizumi, S., Fujishita, K., Shibata, K., Ozawa, T.
  • Organizer: Society for Neuroscience
  • Place of Presentation: Chicago, USA.
  • Year and Date: 20091017-20091021
• [Presentation] Contribution of astrocytes to the "French paradox" in the CNS. (2009)
  • Author(s): Koizumi, S., Fujishita, K., Shibata, K., Ozawa, T., Tanabe, S., Sato, Y.
  • Place of Presentation: Paris, France.
  • Year and Date: 20090908-20090912
• [Presentation] Mechanisms underlying upregulation of P2Y_6 receptors in microglia in kainate-induced injury model. (2009)
  • Author(s): Fujishita, K., Nakao, A., Inoue, K.and Koizumi, S.
  • Place of Presentation: Paris, France.
  • Year and Date: 20090908-20090912
• [Presentation] Cell-to-cell communication mediated by extracellular nucleotides in the CNS. (2009)
  • Author(s): Koizum, S.
  • Organizer: A lecture in commemoration of receiving prize "Japan Academy Medal" Fukuoka Purine 2009
  • Place of Presentation: Fukuoka.
  • Year and Date: 20090723-20090725
• [Presentation] Fujishita, K.Glial function and ischemic brain injury.(シンポジウム) (2009)
  • Author(s): Koizumi, S.
  • Organizer: 第82回日本薬理学会
  • Place of Presentation: 横浜
  • Year and Date: 20090316-20090318
• [Presentation] Astrocyte-to-pericyte communication mediated by ATP. (2008)
  • Author(s): Fujishita, K., Sueishi, K., Takata, F., Kataoka, Y., Koizumi, S.
  • Organizer: Society for Neuroscience
  • Place of Presentation: Washington DC, USA.
  • Year and Date: 20081115-20091119
• [Book] ATPを介したグリア・ニューロン相互作用、細胞 (2008)
  • Author(s): 小泉修一
  • Total Pages: 12(142)-16(146)
  • Publisher: ニューサイエンス社
• [Book] ニューロン・ミクログリア相互作用、BioClinica (2008)
  • Author(s): 小泉修一、井上和秀
  • Total Pages: 97-102
  • Publisher: 北隆館
• [Remarks]
  • URL: http://www.47news.jp/CN/200704/CN2007040501000448.html
• [Patent(Industrial Property Rights)] グリア細胞の活性化抑制組成物 (2009)
  • Inventor(s): 小泉修一(山梨大学)、柴田圭輔(山梨大学)、藤下加代子(山梨大学)、菅原健(山梨大学)、松川隆(山梨大学)
  • Industrial Property Rights Holder: 小泉修一(山梨大学)、柴田圭輔(山梨大学)、藤下加代子(山梨大学)、菅原健(山梨大学)、松川隆(山梨大学)
  • Industrial Property Number: 特願2009-267902
  • Filing Date: 2009-11-25
• [Patent(Industrial Property Rights)] 神経細胞の維持や修復に有用な薬剤 (2009)
  • Inventor(s): 小泉修一(山梨大学)、柴田圭輔(山梨大学)、小澤哲朗(山梨大学)、柴田圭輔(山梨大学)、松川隆(山梨大学)
  • Industrial Property Rights Holder: 小泉修一(山梨大学)、柴田圭輔(山梨大学)、小澤哲朗(山梨大学)、柴田圭輔(山梨大学)、松川隆(山梨大学)
  • Industrial Property Number: 特願2009-183294
  • Filing Date: 2009-08-06