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Regulation of Arc gene transcription by SRF cofactors: mechanism and application for drug design in ASD

Research Project

Project/Area Number 26460064
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionUniversity of Toyama

Principal Investigator

TABUCHI Akiko  富山大学, 大学院医学薬学研究部(薬学), 准教授 (40303234)

Co-Investigator(Renkei-kenkyūsha) Mori Hisashi  富山大学, 大学院医学薬学研究部(医学), 教授 (00239617)
Research Collaborator FUKUCHI Mamoru  富山大学, 大学院医学薬学研究部(薬学), 助教
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords神経活動 / 血清応答因子(SRF) / MKL / Arc / 遺伝子発現 / 転写因子 / SRF / 脳由来神経栄養因子 / 血清応答因子 / 転写コファクター / 脳由来神経栄養因子(BDNF)
Outline of Final Research Achievements

Neuronal activity controls gene expression in neurons and regulates the amounts of molecules which are involved in brain function. Activity-regulated cytoskeleton-associated protein (Arc) functions at synapses. Thus, understanding the molecular mechanism of Arc gene expression contributes to the construction of drug design for neurological disorders. Transcription factors play a central role in gene expression. One of the representative transcription factor is serum response factor (SRF). We have focused on SRF-bound cofactor, megakaryoblastic leukemia (MKL). In this study, we found that MKL2 play an important role in activating Arc gene in neurons. In addition, SOLOIST, a novel MKL2 isoform, which we discovered activated several immediate early genes. We are now generating genetically modified mice to investigate the in vivo function of SOLOIST. Furthermore, we produced MKL1 and MKL2 antibodies.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (38 results)

All 2016 2015 2014 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Acknowledgement Compliant: 1 results,  Open Access: 3 results) Presentation (29 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results) Remarks (2 results)

  • [Journal Article] Balance between cAMP and Ca(2+) signals regulates expression levels of pituitary adenylate cyclase-activating polypeptide gene in neurons.2016

    • Author(s)
      Fukuchi M, Kuwana Y, Tabuchi A, Tsuda M
    • Journal Title

      Genes Cells.

      Volume: 21 Issue: 8 Pages: 921-9

    • DOI

      10.1111/gtc.12393

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Neuromodulatory effect of Gαs- or Gαq-coupled GPCR on NMDAR selectively activates the NMDAR/Ca2+/calcineurin/CREB-regulated transcriptional coactivator 1 (CRTC1) pathway to effectively induce Bdnf expression in neurons.2015

    • Author(s)
      Fukuchi M, Tabuchi A, Kuwana Y, Watanabe S, Inoue M, Takasaki I, Izumi H, Tanaka A, Inoue R, Mori H, Komatsu H, Takamori H, Okuno H, Bito H, Tsuda M.
    • Journal Title

      J Neurosci.

      Volume: 35 Issue: 14 Pages: 5606-5624

    • DOI

      10.1523/jneurosci.3650-14.2015

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Convergent effests of Ca2+ and cAMP signals on the expression of immediate early genes in neurons.2015

    • Author(s)
      Fukuchi M, Kanesaki K, Takasaki I, Tabuchi A, Tsuda M.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 466 (3) Issue: 3 Pages: 572-577

    • DOI

      10.1016/j.bbrc.2015.09.084

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Class I histone deacetylase-mediated repression of the proximal promoter of the activity-regulated cytoskeleton-associated protein gene regulates its response to brain-derived neurotrophic factor.2015

    • Author(s)
      Fukuchi M, Nakashima F, Tabuchi A, Shimotori M, Tatsumi S, Okuno H, Bito H, Tsuda M
    • Journal Title

      J Biol Chem.

      Volume: 290 Issue: 11 Pages: 6825-6836

    • DOI

      10.1074/jbc.m114.617258

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Excitatory GABA induces BDNF transcription via CRTC1 and phosphorylated CREB-related pathways in immature cortical cells.2014

    • Author(s)
      Fukuchi M, Kirikoshi Y, Mori A, Eda R, Ihara D, Takasaki I, Tabuchi A, Tsuda M.
    • Journal Title

      Journal of Neurochemistry

      Volume: 131 Issue: 2 Pages: 134-146

    • DOI

      10.1111/jnc.12801

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transient α-helices in the disordered RPEL motifs of the serum response factor coactivator MKL1.2014

    • Author(s)
      Mizuguchi M, Fuju T, Obita T, Ishikawa M, Tsuda M, Tabuchi A.
    • Journal Title

      Sci Rep.

      Volume: 4 Issue: 1 Pages: 5224-5224

    • DOI

      10.1038/srep05224

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cellular localization and dendritic function of rat isoforms of the SRF coactivator MKL1 in cortical neurons.2014

    • Author(s)
      Ishikawa M, Shiota J, Ishibashi Y, Hakamata T, Shoji S, Fukuchi M, Tsuda M, Shirao T, Sekino Y, Baraban JM, Tabuchi A.
    • Journal Title

      Neuroreport.

      Volume: 25 Issue: 8 Pages: 585-92

    • DOI

      10.1097/wnr.0000000000000141

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] 高品質抗体を利用したSRF転写活性化因子MKL1とMKL2のシナプスにおける局在と機能の解析2016

    • Author(s)
      田渕明子,金田真理彩,菊池啓悦,佐藤夏美,石橋悠太,阪上洋行,大塚稔久,飛田耶馬人,福地 守,津田正明
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] 脳神経系における転写因子SRFとそのコファクターの発現と機能2016

    • Author(s)
      田渕明子
    • Organizer
      第3回北陸エピジェネティクス研究会
    • Place of Presentation
      福井
    • Year and Date
      2016-11-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] Monitoring and visualizing changes in the expression of BDNF gene using bioluminescence imaging.2016

    • Author(s)
      Fukuchi M, Mori H, Tabuchi A, Tsuda M.
    • Organizer
      Society for Neuroscience 46th annual meeting
    • Place of Presentation
      SanDiego
    • Year and Date
      2016-11-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Specific detection of SRF transcriptional coactivator MKL1 and MKL2 by using new antibodies: application to visualization of subcellular localization in neurons.2016

    • Author(s)
      Kaneda M, Sakagami H, Fukuchi M, Tsuda M, Tabuchi A
    • Organizer
      The First International Symposium on Toyama-Asia-Africa Pharmaceutical Network
    • Place of Presentation
      Toyama
    • Year and Date
      2016-09-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification and characterization of SOLOIST, a novel neuronal isoform of SRF coactivator MKL2: comparison to other MKL2 isoforms.2016

    • Author(s)
      Tanaka T, Ishibashi Y, Shoji S, Kubo Y, Hakamata T, Sakagami H, Fukuchi M, Okuno H, Bito H, Tsuda M
    • Organizer
      The First International Symposium on Toyama-Asia-Africa Pharmaceutical Network
    • Place of Presentation
      Toyama
    • Year and Date
      2016-09-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Involvement of SRF cofactors MKL and TCF in BDNF-induced Arc gene promoter regulation in cortical neurons.2016

    • Author(s)
      Tabuchi A, Kikuchi K, Fukuchi M, Ishibashi Y, Tsujii J, Okuno H, Bito H, Tsuda M
    • Organizer
      The First International Symposium on Toyama-Asia-Africa Pharmaceutical Network
    • Place of Presentation
      Toyama
    • Year and Date
      2016-09-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] BDNF-Lucマウスを利用したBDNF遺伝子発現変化の可視化およびBDNF遺伝子発現誘導剤の探索2016

    • Author(s)
      福地 守,前畑陽祐,森 寿,牧昌次郎,田渕明子,津田正明
    • Organizer
      第38回日本生物学的精神医学会第59回日本神経化学会大会合同大会
    • Place of Presentation
      福岡
    • Year and Date
      2016-09-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] Evaluation of new antibodies against SRF coactivator MKL1 and MKL2.2016

    • Author(s)
      金田真理彩,阪上洋行,福地 守,津田正明,田渕明子
    • Organizer
      第38回日本生物学的精神医学会第59回日本神経化学会大会合同大会
    • Place of Presentation
      福岡
    • Year and Date
      2016-09-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] SOLOIST, a novel neuronal isoform of SRF coactivator MKL2, but not other isoforms, activates endogenous Arc gene transcription in neuronal cells.2016

    • Author(s)
      田中拓郎,石橋悠太,庄司しずく,久保友喜美,袴田知之,阪上洋行,福地 守,奥野浩行,尾藤晴彦,津田正明,田渕明子
    • Organizer
      第38回日本生物学的精神医学会第59回日本神経化学会大会合同大会
    • Place of Presentation
      福岡
    • Year and Date
      2016-09-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] 神経可塑性関連遺伝子の発現調節におけるCREBおよびSRFコファクターの役割2016

    • Author(s)
      田渕明子,福地 守,菊池啓悦,久保友喜美,庄司しずく,袴田知之,田中拓郎,佐藤夏美,石橋悠太,阪上洋行,尾藤晴彦,奥野浩行,大塚稔久,津田正明
    • Organizer
      第39回日本神経科学大会シンポジウム「神経活動依存的な遺伝子発現の制御と機能」
    • Place of Presentation
      横浜
    • Year and Date
      2016-07-20
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 生物発光イメージングを利用した生体マウスにおけるBDNF発現変化の可視化2016

    • Author(s)
      福地 守,和泉宏謙,田中亜由美,井上 蘭,森 寿,牧昌次郎,木山正啓,大塚智史,前畑陽祐,津田正明
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      横浜
    • Year and Date
      2016-07-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] SRF 転写活性化因子 MKL1 および MKL2 のポストシナプス局在とその意義2016

    • Author(s)
      金田真理彩,阪上洋行,佐藤夏美,石橋悠太、福地 守,津田正明,田渕明子
    • Organizer
      日本薬学会北陸支部第128回例会
    • Place of Presentation
      金沢
    • Related Report
      2016 Annual Research Report
  • [Presentation] SRFコアクチベーターMKL2の新規アイソフォームSOLOISTの発現と機能解析.2015

    • Author(s)
      田中拓郎,石橋悠太,庄司しずく,久保友喜美,袴田知之,阪上洋行,福地守,津田正明,田渕明子.
    • Organizer
      日本薬学会北陸支部第127回例会
    • Place of Presentation
      富山
    • Year and Date
      2015-11-15
    • Related Report
      2015 Research-status Report
  • [Presentation] 神経ペプチドPACAP誘導性CRE依存的転写活性化におけるアンカータンパク質AKAP150の役割.2015

    • Author(s)
      渡邊漠,福地守,市村美奈,越智雄基,田渕明子,津田正明.
    • Organizer
      日本薬学会北陸支部第127回例会
    • Place of Presentation
      富山
    • Year and Date
      2015-11-15
    • Related Report
      2015 Research-status Report
  • [Presentation] 異なる翻訳開始点から合成されるBDNFタンパクの相違.2015

    • Author(s)
      雑賀美友紀,福地守,田渕明子,津田正明.
    • Organizer
      日本薬学会北陸支部第127回例会
    • Place of Presentation
      富山
    • Year and Date
      2015-11-15
    • Related Report
      2015 Research-status Report
  • [Presentation] Regulation of BDNF gene expression and its possible role in neural functions and diseases.2015

    • Author(s)
      Fukuchi M, Tabuchi A, Tsuda M.
    • Organizer
      第58回日本神経化学会大会
    • Place of Presentation
      さいたま
    • Year and Date
      2015-09-11
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] SOLOIST, a novel isoform of SRF coactivator MKL2 that is enriched in neurons and negatively regulates dendritic complexity of cortical neurons.2015

    • Author(s)
      Tanaka T, Ishibashi Y, Shoji S, Kubo Y, Hakamata T, Sakagami H, Fukuchi M, Tsuda M, Tabuchi A.
    • Organizer
      第58回日本神経化学会大会
    • Place of Presentation
      さいたま
    • Year and Date
      2015-09-11
    • Related Report
      2015 Research-status Report
  • [Presentation] PACAP induces Bdnf expression through selective activation of NMDA receptor/calcineurin pathway in neurons.2015

    • Author(s)
      Watanabe B, Fukuchi M, Ichimura M, Ochi Y, Tabuchi A, Tsuda M.
    • Organizer
      第58回日本神経化学会大会
    • Place of Presentation
      さいたま
    • Year and Date
      2015-09-11
    • Related Report
      2015 Research-status Report
  • [Presentation] Difference in a translation start site in BDNF exon I and exon IX.2015

    • Author(s)
      Saika M, Fukuchi M, Tabuchi A, Tsuda M.
    • Organizer
      第58回日本神経化学会大会
    • Place of Presentation
      さいたま
    • Year and Date
      2015-09-11
    • Related Report
      2015 Research-status Report
  • [Presentation] クラスⅠHDACはArc遺伝子プロモーターの近傍領域を介してBDNF誘導性Arc発現を抑制する.2015

    • Author(s)
      福地守,中島布久美,田渕明子,奥野浩行,尾藤晴彦,津田正明.
    • Organizer
      第38回日本神経科学大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-07-28
    • Related Report
      2015 Research-status Report
  • [Presentation] Rho-SRFシグナル阻害剤がラット大脳皮質神経細胞のSRF介在性遺伝子発現と形態に与える効果.2015

    • Author(s)
      菊池啓悦,塩田惇,山田哲也,福地守,津田正明,田渕明子.
    • Organizer
      第38回日本神経科学大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-07-28
    • Related Report
      2015 Research-status Report
  • [Presentation] SRFコアクチベーターMKLによるBDNF誘導性Arc遺伝子発現制御機構の解析.2015

    • Author(s)
      菊地啓悦,福地守,石橋悠太,辻井惇也,石川充,津田正明,奥野浩行,尾藤晴彦,田渕明子.
    • Organizer
      日本生化学会北陸支部第33回大会
    • Place of Presentation
      富山
    • Year and Date
      2015-05-23
    • Related Report
      2015 Research-status Report
  • [Presentation] GPCR活性化によるNMDAR/カルシニューリン/CRTC1経路の選択的活性化を介した遺伝子発現誘導.2014

    • Author(s)
      福地守,前畑陽祐,和泉宏謙,田中亜由美,井上蘭,森寿,田渕明子,津田正明.
    • Organizer
      第36回日本生物学的精神医学会・第57回日本神経化学会大会合同年会
    • Place of Presentation
      奈良
    • Year and Date
      2014-09-29 – 2014-10-01
    • Related Report
      2014 Research-status Report
  • [Presentation] 神経細胞に高発現するScapinin/Phactr3のアクチンとPP1結合部位による樹状突起形態制御.2014

    • Author(s)
      田渕明子,宮田智陽,皆藤真季,菊池啓悦,石橋悠太,福地守,袴田知之,津田正明.
    • Organizer
      第36回日本生物学的精神医学会・第57回日本神経化学会大会合同年会
    • Place of Presentation
      奈良
    • Year and Date
      2014-09-29 – 2014-10-01
    • Related Report
      2014 Research-status Report
  • [Presentation] Expression and dendritic roles of actin- and protein phosphatase-1-binding protein, Scapinin/Phactr3, in rat cortical neurons.2014

    • Author(s)
      Tabuchi A, Miyata T, Kaito M, Kikuchi K, Ishibashi Y, Fukuchi M, Hakamata T, Tsuda M.
    • Organizer
      6th Special Conference of The International Society for Neurochemistry
    • Place of Presentation
      東京
    • Year and Date
      2014-09-20 – 2014-09-22
    • Related Report
      2014 Research-status Report
  • [Presentation] V-1遺伝子によるアクチン重合依存的な黒質線条体ドパミン生合成酵素群の統合的新規発現制御機構.2014

    • Author(s)
      川畑伊知郎,延新来,大宅史織,森田淳一,加藤茂樹,富岡佳久,田渕明子,福地守,津田正明,一瀬-鷲見千穂,近藤一直,泉安彦,久米利明,赤池昭紀,大橋一正,水野健作,一瀬宏,小林和人,山国徹.
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      神奈川
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] PACAPによるBDNF遺伝子発現誘導 - 生物発光イメージングを利用した解析.2014

    • Author(s)
      福地守,前畑陽祐,和泉宏謙,田中亜由美,井上蘭,森寿,田渕明子,津田正明
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      神奈川
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] SRF転写コファクターMKL2のアイソフォーム発現と樹状突起形態制御.2014

    • Author(s)
      田渕明子,石橋悠太,庄司しずく,久保友喜美,袴田知之,宮田智陽,佐藤夏美,阪上洋行,福地守,津田正明
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      神奈川
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] 発光イメージングを用いた神経ペプチドPACAPによる脳由来神経栄養因子BDNF遺伝子発現誘導機構の解析.2014

    • Author(s)
      福地守,田渕明子,前畑陽祐,和泉宏謙,田中亜由美,井上蘭,森寿,津田正明
    • Organizer
      日本生化学会北陸支部第32回大会
    • Place of Presentation
      富山
    • Year and Date
      2014-05-24
    • Related Report
      2014 Research-status Report
  • [Remarks] 富山大学薬学部分子神経生物学研究室

    • URL

      http://www.pha.u-toyama.ac.jp/laboratory/bioche1/index.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 富山大学薬学部分子神経生物学研究室

    • URL

      http://www.pha.u-toyama.ac.jp/bioche1/index-j.html

    • Related Report
      2015 Research-status Report 2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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