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Functional analysis of G-protein coupled receptor 3 for future applications of novel stroke therapy utilizing neuronal stem cell transplantation

Research Project

Project/Area Number 24591264
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionHiroshima University

Principal Investigator

TANAKA Shigeru  広島大学, 医歯薬保健学研究院, 講師 (20512651)

Co-Investigator(Kenkyū-buntansha) MATSUMOTO Masayasu  広島大学, 医歯薬保健学研究院, 教授 (20192346)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsGPCR / cAMP / PKA / 神経細胞 / Neuron / cAMP
Outline of Final Research Achievements

G-protein coupled receptor 3 (GPR3) belongs to a member of constitutively active Gs-coupled receptors that activate 3’-5’-cyclic adenosine monophosphate (cAMP) and is highly expressed in the brain. In the current study, principal investigator has clarified that GPR3 was distributed in the cortex, striatum, hippocampus, medial habenular nucleus, and cerebellum. The GPR3 subcellular localization analysis using fluorescent-tagged GPR3 revealed that GPR3 was distributed along the plasma membrane and in goldi bodies and endosomes in neurons. Moreover, time-lapse experiments revealed that fluorescent punctae of GPR3 were transported along the neurite, which was associated with the local activation of PKA at the neurite tips.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (50 results)

All 2015 2014 2013 2011 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (39 results) (of which Invited: 1 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Deregulation of the actin cytoskeleton and macropinocytosis in response to phorbol ester by the mutant protein kinase C gamma that causes spinocerebellar ataxia type 14.2014

    • Author(s)
      Yamamoto K, Seki T, Yamamoto H, Adachi N, Tanaka S, Hide I, Saito N, Sakai N
    • Journal Title

      Front Physiol.

      Volume: 5 Pages: 126-126

    • DOI

      10.3389/fphys.2014.00126

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Developmental expression of GPR3 in rodent cerebellar granule neurons is associated with cell survival and protects neurons from various apoptotic stimuli.2014

    • Author(s)
      Tanaka S, Miyagi T, Dohi E, Seki T, Hide I, Sotomaru Y, Saeki Y, Chiocca AE, Matsumoto M, Sakai N
    • Journal Title

      Neurobiol Dis.

      Volume: 68 Pages: 215-227

    • DOI

      10.1016/j.nbd.2014.04.007

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Long-Term Exposure of RN46A Cells Expressing Serotonin Transporter (SERT) to a cAMP Analog Up-regulates SERT Activity and Is Accompanied by Neural Differentiation of the Cells2013

    • Author(s)
      Yamamoto, H
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 121 Issue: 1 Pages: 25-38

    • DOI

      10.1254/jphs.12229FP

    • NAID

      10031147584

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of the Chemical Chaperone 4-Phenylbutylate on the Function of the Serotonin Transporter (SERT) Expressed in COS-7 Cells2013

    • Author(s)
      Fujiwara, M., Yamamoto, H., Miyagi, T., Seki, T., Tanaka, S., Hide, I., Sakai, N.
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 122 Issue: 2 Pages: 71-83

    • DOI

      10.1254/jphs.12194FP

    • NAID

      10031185399

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A brain-specific Grb2-associated regulator of extracellular signal-regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) (GAREM) subtype, GAREM2, contributes to neurite outgrowth of neuroblastoma cells by regulating Erk signaling.2013

    • Author(s)
      Taniguchi T, Tanaka S, Ishii A, Watanabe M, Fujitani N, Sugeo A, Gotoh S, Ohta T, Hiyoshi M, Matsuzaki H, Sakai N, Konishi H.
    • Journal Title

      J Biol Chem.

      Volume: 288 Issue: 41 Pages: 29934-29942

    • DOI

      10.1074/jbc.m113.492520

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mutant gammaPKC that causes spinocerebellar ataxia type 14 upregulates Hsp70, which protects cells from the mutant's cytotoxicity.2013

    • Author(s)
      Ogawa, K., Seki, T., Onji, T., Adachi, N., Tanaka, S., Hide, I., Saito, N., Sakai, N.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 440 Issue: 1 Pages: 25-30

    • DOI

      10.1016/j.bbrc.2013.09.013

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of the chemical chaperone 4-phenylbutylate on the function of the serotonin transporter (SERT) expressed in COS-7 cells.2013

    • Author(s)
      Fujiwara, M., Yamamoto, H., Sakai, N., et al
    • Journal Title

      J. Pharmacol. Sci.

      Volume: in press

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Establishment of a novel fluorescence-based method to evaluate chaperone-mediate autophagy in a singlz neuron2011

    • Author(s)
      Seki, T., Ki Y., Tanaka, S., Dohi, E., Onji, T., Yamamoto, K., Seki T, Yoshino KI, Tanaka S, Dohi E, Onji T, Yamamoto K, Hide, I., Sakai, N. et al.
    • Journal Title

      PLoS ONE

      Volume: 7 Issue: 2 Pages: e31232-e31232

    • DOI

      10.1371/journal.pone.0031232

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hypoxic stress activates chaperone-mediated autophagy and modulates neuronal cell survival2011

    • Author(s)
      Dohi, E., Tanaka, S., Seki, T, m Miyagi, T., Hide, I., Sakai, N. et al.
    • Journal Title

      Neurochemistry International

      Volume: 60 Issue: 4 Pages: 431-442

    • DOI

      10.1016/j.neuint.2012.01.020

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 虚血性脳障害において神経細胞生存に関連するG蛋白共役型受容体GPR32015

    • Author(s)
      田中茂、宮城達博、土肥栄祐、秀和泉、佐伯嘉修、E. Antonio Chiooca、松本昌泰、酒井規雄
    • Organizer
      第40回脳卒中学会総会
    • Place of Presentation
      広島グリーンアリーナ(広島)
    • Year and Date
      2015-03-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] 神経細胞における恒常的Gs活性化受容体GPR3の機能2015

    • Author(s)
      田中茂、佐伯嘉修、E. Antonio Chiocca、酒井規雄
    • Organizer
      第88回日本薬理学会年会シンポジウム
    • Place of Presentation
      名古屋国際会議場(名古屋)
    • Year and Date
      2015-03-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] TLR4活性化ミクログリアはGM-CSFシグナルを上方制御しその生存を維持する2015

    • Author(s)
      神垣真由美、秀和泉、白榊紘子、柳瀬雄輝、田中茂、白藤俊彦、秀道広、酒井規雄
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(名古屋)
    • Year and Date
      2015-03-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Neuronal expression of GPR3 in rodent brain is associated with cell survival2014

    • Author(s)
      Tanaka S, Miyagi T, Hide I, Shirafuji T, and Sakai N
    • Organizer
      Society for Neuroscience meeting 2014
    • Place of Presentation
      米国ワシントンDC
    • Year and Date
      2014-11-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] The subcellular localization and local function of Gs-linked receptor GPR3 in neuronal cells2014

    • Author(s)
      Miyagi T, Tanaka S, Hide I, Shirafuji T, and Sakai N
    • Organizer
      Society for Neuroscience meeting 2014
    • Place of Presentation
      米国ワシントンDC
    • Year and Date
      2014-11-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Mechanism of TLR4-mediated survival of microglia: Roles of GM-CSF self-production and the activation of JAK2/STAT5 signaling pathwaysvation of JAK2/STAT5 signaling pathways2014

    • Author(s)
      Kamigaki M, Hide I, Yanase Y, Tanaka S, Shirafuji T, Hide M, Sakai N
    • Organizer
      Society for Neuroscience meeting 2014
    • Place of Presentation
      米国ワシントンDC
    • Year and Date
      2014-11-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 小脳顆粒神経細胞における恒常的Gs活性型受容体GPR3の局在と機能2014

    • Author(s)
      宮城達博、田中茂、秀和泉、白藤俊彦、酒井規雄
    • Organizer
      第126回薬理学会近畿部会
    • Place of Presentation
      和歌山JAビル(和歌山)
    • Year and Date
      2014-10-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] GPR3は様々なアポトーシス刺激に対し神経保護的に働く2014

    • Author(s)
      田中茂、宮城達博、秀和泉、白藤俊彦、酒井規雄
    • Organizer
      第57回日本神経化学大会
    • Place of Presentation
      奈良県文化会館・奈良県新講堂(奈良市)
    • Year and Date
      2014-10-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] GM-CSF自己産生とJAK2/STAT5シグナル伝達がTLR4活性化ミクログリアの生存に関与する2014

    • Author(s)
      神垣真由美、秀和泉、柳瀬雄輝、白榊紘子、田中茂、白藤俊彦、秀道広、酒井規雄
    • Organizer
      第57回日本神経化学大会
    • Place of Presentation
      奈良県文化会館・奈良県新講堂(奈良市)
    • Year and Date
      2014-10-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] 神経細胞におけるGs共役型受容体GPR3の細胞内動態と機能2014

    • Author(s)
      宮城達博、田中茂、秀和泉、白藤俊彦、酒井規雄
    • Organizer
      第57回日本神経化学大会
    • Place of Presentation
      奈良県文化会館・奈良県新講堂(奈良市)
    • Year and Date
      2014-09-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] 脳虚血環境下における神経細胞生存の分子メカニズム2014

    • Author(s)
      田中茂
    • Organizer
      広島大学脳神経内科 WNNM研究会
    • Place of Presentation
      広島リーガロイヤルホテル(広島)
    • Year and Date
      2014-09-16
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] TLR4活性化ミクログリアはGM-CSFの自己産生とJAK2/STAT5シグナル伝達を介して生存を維持する2014

    • Author(s)
      神垣真由美、秀和泉、柳瀬雄輝、田中茂、白藤俊彦、秀道広、酒井規雄
    • Organizer
      第125回日本薬理学会近畿部会
    • Place of Presentation
      岡山コンベンションセンター(岡山)
    • Year and Date
      2014-06-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 齧歯類脳虚血モデルにおけるCMA関連蛋白LAMP-2Aの経時的発現変化2013

    • Author(s)
      土肥栄祐、田中茂、関貴弘、宮城達博、秀和泉、高橋哲也、松本昌泰、酒井規雄
    • Organizer
      第54回神経学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] イメージングを活用した新たなシャペロン介在性オートファジーの解析方法の確立2013

    • Author(s)
      酒井規雄、吉野健一、田中茂、土肥栄祐、隠地智也、山本和央、秀和泉、Henly L Paulson、齋藤尚亮、関貴弘
    • Organizer
      第54回神経学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] TLR4活性化によるミクログリアの生存維持にGM-CSF自己産生とTNF/TNFR2シグナルが関与する

    • Author(s)
      神垣真由美、秀和泉、柳瀬雄輝、田中芳樹、原田佳奈、関貴弘、田中茂、秀道広、酒井規雄
    • Organizer
      Neuro2013
    • Place of Presentation
      京都国際会議場
    • Related Report
      2013 Research-status Report
  • [Presentation] 神経細胞における恒常的Gs活性化受容体GPR3の局在と機能

    • Author(s)
      宮城達博、田中茂、秀和泉、関貴弘、酒井規雄
    • Organizer
      Neuro2013
    • Place of Presentation
      京都国際会議場
    • Related Report
      2013 Research-status Report
  • [Presentation] 膜輸送によるセロトニントランスポーター調節機構

    • Author(s)
      酒井規雄、藤原雅幸、山本光、浅野昌也 田中茂、関貴弘、秀和泉
    • Organizer
      第17回活性アミンに関するワークショップ
    • Place of Presentation
      福井
    • Related Report
      2013 Research-status Report
  • [Presentation] 中枢神経系における恒常的Gs活性型受容体GPR3の局在と機能

    • Author(s)
      宮城達博、田中茂、秀和泉、関貴弘、酒井規雄
    • Organizer
      第43回神経精神薬理学会総会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Research-status Report
  • [Presentation] 蛍光イメージングを用いた神経細胞でのシャペロン介在性オートファジー活性の解析

    • Author(s)
      関貴弘、吉野健一、田中茂、土肥栄祐、隠地智也、秀和泉、Henly Paulson、齋藤尚亮、酒井規雄
    • Organizer
      第43回神経精神薬理学会総会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Research-status Report
  • [Presentation] セロトニントランスポーター機能調節に対するケミカルシャペロン4-phenylbutylate(4-PBA)の効果

    • Author(s)
      酒井規雄、藤原雅幸、山本光、宮城達博、関貴弘、田中茂、秀和泉
    • Organizer
      第43回神経精神薬理学会総会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Research-status Report
  • [Presentation] GPR3 protects neurons from apoptosis via Phosphatidylinositol 3-Kinase and mitogen-activated protein-kinase signaling pathway.

    • Author(s)
      Tanaka S, Miyagi T, Hide I, Seki T, and Sakai N
    • Organizer
      Neuroscience meeting 2013
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Possible relationship between decreased expression of lysosomal-associated membrane protein type 2A and delayed neuronal death after brain ischemia.

    • Author(s)
      Dohi E, Tanaka S, Seki T, Hide I, Matsumoto M, and Sakai N
    • Organizer
      Neuroscience meeting 2013
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] GPR3は様々なアポトーシス刺激に対し神経保護的に働く

    • Author(s)
      田中茂、宮城達博、秀和泉、白藤俊彦、E. Antonio Chiocca、酒井規雄
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] 神経細胞における恒常的Gs活性化受容体GPR3の細胞内局在と機能

    • Author(s)
      宮城達博、田中茂、秀和泉、白藤俊彦、酒井規雄
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] LR4を介したアデノシンA2a受容体活性化によるミクログリア機能の調節

    • Author(s)
      秀和泉、神垣真由美、柳瀬雄輝、関貴弘、田中茂、白藤俊彦、秀道広、酒井規雄
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] 低酸素ストレスにより活性化されるシャペロン介在性オートファジーの細胞保護効果

    • Author(s)
      土肥栄佑 田中茂 酒井規雄 他
    • Organizer
      第121回薬理学会近畿部会
    • Place of Presentation
      徳島
    • Related Report
      2012 Research-status Report
  • [Presentation] 神経細胞株SH-SY 5Y細胞におけるニコチン誘発性PKCトランスロケーションの観察

    • Author(s)
      酒井規雄 宮原岳史 田中茂 他
    • Organizer
      第16回活性アミンに関するワークショップ
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] GPR3依存的な神経突起伸長にPI3キナーゼ、MAPキナーゼの活性化が寄与する

    • Author(s)
      田中茂 宮城達博 酒井規雄 他
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] GPR3 protects neurons from apoptosis under the hypoxic condition.

    • Author(s)
      Tanaka, S., Miyagi, M Sakai, N. et al
    • Organizer
      第55回日本神経化学会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] Enhanced survival and phagocyticactivity by Toll-like receptor 4 activation in rat microglia.

    • Author(s)
      Hide, I. Yanase, Y Sakai, N. et al
    • Organizer
      第55回日本神経化学会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] Long-term exposure of cAMP analogue up-regulates the function of serotonin transporter (SERT) in RN46A cells.

    • Author(s)
      Yamamoto, H. Tanaka, S. Sakai, N. et al
    • Organizer
      Neuroscience 2012 (Annual meeting of society for neuroscience)
    • Place of Presentation
      New Orleans (USA)
    • Related Report
      2012 Research-status Report
  • [Presentation] Phosphatidylinositol 3-Kinase and mitogen-activated protein-kinase signaling pathway play a role in the GPR3-mediated neurite outgrowth.

    • Author(s)
      Tanaka, S. Miyagi, T. Sakai, N. et al
    • Organizer
      Neuroscience 2012 (Annual meeting of society for neuroscience)
    • Place of Presentation
      New Orleans (USA)
    • Related Report
      2012 Research-status Report
  • [Presentation] Time dependent alternations of lysosomal-associated membrane protein type 2A in rodent brain following cerebral ischemia.

    • Author(s)
      Dohi E, Tanaka S, Sakai N. et al.
    • Organizer
      Neuroscience 2012 (Annual meeting of society for neuroscience)
    • Place of Presentation
      New Orleans (USA)
    • Related Report
      2012 Research-status Report
  • [Presentation] GPR3 protects neurons from apoptosis, induced by different stimuli

    • Author(s)
      Tanaka S, Miyagi T, Sakai N. et al.
    • Organizer
      Transpacific Workshop on Stroke
    • Place of Presentation
      New Orleans (USA)
    • Related Report
      2012 Research-status Report
  • [Presentation] Contribution of chaperone-mediated autophagy to the survival of cells under the hypoxic conditions.

    • Author(s)
      Dohi E, Tanaka S, Sakai N. et al.
    • Organizer
      Transpacific Workshop on Stroke
    • Place of Presentation
      New Orleans (USA)
    • Related Report
      2012 Research-status Report
  • [Presentation] 虚血脳におけるシャペロン介在性オートファジーの役割

    • Author(s)
      田中茂 土肥栄祐 酒井規雄 他
    • Organizer
      第24回脳循環代謝学会総会シンポジウム
    • Place of Presentation
      広島
    • Related Report
      2012 Research-status Report
  • [Presentation] ミクログリアの死細胞貪食におけるP2Y2受容体の役割

    • Author(s)
      秀和泉 田中茂 酒井規雄 他
    • Organizer
      第122回日本薬理学会近畿部会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Presentation] GPR3を介した突起伸長にGbetagannmaを介する経路が部分的に関与する

    • Author(s)
      田中茂 宮城達博 酒井規雄 他
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Toll様受容体4活性化により生存するミクログリアは顆粒球マクロファージコロニー刺激因子を自己誘導する

    • Author(s)
      神垣真由美 秀和泉 酒井規雄 他
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Book] 最新臨床脳卒中学(上)2014

    • Author(s)
      田中茂、土肥栄祐、酒井規雄 (分担執筆)
    • Total Pages
      735
    • Publisher
      日本臨床
    • Related Report
      2014 Annual Research Report
  • [Remarks] 広島大学大学院 医歯薬保健学研究科 神経薬理学

    • URL

      http://home.hiroshima-u.ac.jp/yakuri/

    • Related Report
      2014 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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