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Roles of Girdin in synaptic plasticity and memory

Research Project

Project/Area Number 24390095
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionNagoya University

Principal Investigator

ASAI Naoya  名古屋大学, 医学(系)研究科(研究院), 准教授 (80273233)

Co-Investigator(Kenkyū-buntansha) NAGAI Taku  名古屋大学, 医学部附属病院, 准教授 (10377426)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2013: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywords記憶障害 / シナプス可塑性 / 蛋白リン酸化 / 疾患モデルマウス / BDNF/TekB/Akiシグナル / 海馬神経 / 蛋白リン酸 / アクチン結合蛋白 / 行動解析
Outline of Final Research Achievements

Girdin, an actin-binding protein involved both in the remodeling of the actin cytoskeleton and in cell migration, has been identified as a substrate of Akt at Girdin S1416. We focused on the role of Girdin S1416 phosphorylation in BDNF/TrkB/Akt signaling associated with synaptic plasticity. We found that Girdin in the hippocampus was phosphorylated at S1416 in an activity-dependent manner. Phosphorylation-deficient knock-in mice exhibited shrinkage of spines, deficit of hippocampal long-term potentiation, and memory impairment. Furthermore, Girdin interacted with Src kinase and NR2B subunit of NMDA receptor, leading to phosphorylation of the NR2B subunit and NMDA receptor activation. Our findings suggest that Girdin controls Akt-dependent NR2B phosphorylation through the interaction with Src, which is associated with synaptic plasticity in the hippocampus underlying memory formation.

Report

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

Research Products

(11 results)

All 2015 2014 2013 2012 Other

All Journal Article Remarks

  • [Journal Article] Akt-Girdin signaling in cancer-associated fibroblasts contributes to tumor progression2015

    • Author(s)
      Yumiko Yamamura, Naoya Asai, Atsushi Enomoto, Takuya Kato, Shinji Mii, Yuji Kondo, Kaori Ushida, Kaoru Niimi, Nobuyuki Tsunoda, Masato Nagino, Shu Ichihara, Koichi Furukawa, Kengo Maeda, Toyoaki Murohara, Masahide Takahashi
    • Journal Title

      Cancer Res,

      Volume: 75 Pages: 813-23

    • DOI

      10.1158/0008-5472.can-14-1317

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Girdin is phosphorylated on tyrosine 1798 when associated with structures required for migration.2015

    • Author(s)
      Kenji Omori, Masato Asai, Daisuke Kuga, Kaori Ushida, Tetsuya Izuchi, Shinji Mii, Atsushi Enomoto, Naoya Asai, Masato Nagino, Masahide Takahashi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 458 Pages: 934-40

    • DOI

      10.1016/j.bbrc.2015.02.065

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Girdin phosphorylation is crucial for synaptic plasticity and memory: a potential role in the interaction of BDNF/TrkB/Akt signaling with NMDA receptor2014

    • Author(s)
      Tsuyoshi Nakai, Taku Nagai, Motoki Tanaka, Norimichi Itoh, Naoya Asai, Atsushi Enomoto, Masato Asai, Shinnnosuke Yamada, Ali Bin Saifullah, Masahiro Sokabe, Masahide Takahashi, Kiyofumi Yamada
    • Journal Title

      J. Neurosci.

      Volume: 34 Pages: 14995-15008

    • DOI

      10.1523/jneurosci.2228-14.2014

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Speed control for neuronal migration in the postnatal brain by Gmip-mediated local inactivation of RhoA.2014

    • Author(s)
      Haruko Ota, Takao Hikita, Masato Sawada, Tomoki Nishioka, Mami Matsumoto, Masayuki Komura, Akihisa Ohno, Yukiyo Kamiya, Takuya Miyamoto, Naoya Asai, Atsushi Enomoto, Masahide Takahashi, Kozo Kaibuchi, Kazuya Sobue, Kazunobu Sawamoto
    • Journal Title

      Nat. Commun.

      Volume: 5 Pages: 4532-4532

    • DOI

      10.1038/ncomms5532

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Regulation of cargo‐selective endocytosis by dynamin 2 GTPase‐activating protein girdin2014

    • Author(s)
      Liang Weng, Atsushi Enomoto, Hiroshi Miyoshi, Kiyofumi Takahashi, Naoya Asai, Nobuhiro Morone, Ping Jiang, Jian An, Takuya Kato, Keisuke Kuroda, Takashi Watanabe, Masato Asai, Maki Ishida-Takagishi, Yoshiki Murakumo, Hideki Nakashima, Kozo Kaibuchi and Masahide Takahashi.
    • Journal Title

      EMBO Journal

      Volume: 33 Pages: 2098-112

    • DOI

      10.15252/embj.201488289

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] ole of Girdin in intimal hyperplasi a in vein grafts and efficacy of at elocollagen-mediated application of small interfering RNA for vein gra ft failure2014

    • Author(s)
      Hiroki Miyachi, Shinji Mii, Atsushi Enomoto, Yoshiki Murakumo, Takuya Kato, Naoya Asai, Kimihiro Komori, Masahide Takahashi
    • Journal Title

      J Vasc Surg

      Volume: 60 Pages: 479-489

    • DOI

      10.1016/j.jvs.2013.06.080

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Proteomic analysis of Girdin-interacting proteins in migrating new neurons in the postnatal mouse brain.2013

    • Author(s)
      Haruko Ota, Takao Hikita, Tomoki Nishioka, Mami Matsumoto, Jun Ito, Naoya Asai, Atsushi Enomoto, Masahide Takahashi, Kozo Kaibuchi, Kazuya Sobue, Kazunobu Sawamoto
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 442 Pages: 16-21

    • DOI

      10.1016/j.bbrc.2013.10.126

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Girdin and its phosphorylation dynamically regulate neonatal vascular development and pathological neovascularization in the retina.2013

    • Author(s)
      Takanori Ito, Keiichi Komeima, Tetsuhiro Yasuma, Atsushi Enomoto, Naoya Asai, Masato Asai, Sayoko Iwase, Masahide Takahashi, Hiroko Terasaki
    • Journal Title

      Am J Pathol

      Volume: 182 Pages: 586-596

    • DOI

      10.1016/j.ajpath.2012.10.012

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Similar phenotypes of Girdin germ-line and conditional knockout mice indicate a crucial role for Girdin in the nestin lineage.2012

    • Author(s)
      Masato Asai
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 426 Pages: 533-538

    • DOI

      10.1016/j.bbrc.2012.08.122

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] nvolvement of Girdin in the determination of cell polarity during cell migration.2012

    • Author(s)
      Ohara K, Enomoto A, et al.
    • Journal Title

      PloS One

      Volume: 7

    • DOI

      10.1371/journal.pone.0036681

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Remarks]

    • URL

      http://www.med.nagoya-u.ac.jp/patho2/

    • Related Report
      2012 Annual Research Report

URL: 

Published: 2012-04-23   Modified: 2019-07-29  

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