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Roles of Girdin in neural and cancer cell migration along vessels

Research Project

Project/Area Number 15K08399
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-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, 准教授 (80273233)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords脳神経発生 / チロシンリン酸化 / GEF活性 / 遺伝子改変動物 / 細胞移動 / タンパク質リン酸化 / 中枢神経の発生 / 線維化 / 細胞運動 / 蛋白リン酸化 / 疾患モデルマウス / 癌 / 神経
Outline of Final Research Achievements

Girdin play important roles for brain development at hippocampus, olfacrory blub/RMS, anterior commissure and GABAergic neurons of cortex. Girdin has two tyrosine phosphorylation sites and GEF domain, but these functions in vivo have not been clear.
To study the function of Girdin tyrosine phosphorylation at Y1764 and Y1798, we generated Girdin Y1764,1798F mutant mice. Mutant mice show no obvious phenotype at hippocampus and olfactory bulb/RMS, which may indicate the less important roles of Girdin tyrosine phosphorylation for cell motility at developing brain. In addition, we generate Girdin F1696A mutant mice, which would lack GEF activity of Girdin. Mutant mice show abnormal brain structure at hippocampus and olfactory blub/RMS resembling Girdin knockout mice. Mutant mice also show milder phenotypes at anterior commissure and distribution of GABAergic neurons in cortex. These data suggest importance of Girdin GEF activity for cell motility.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (15 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (12 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 8 results,  Acknowledgement Compliant: 2 results) Remarks (2 results)

  • [Int'l Joint Research] University of Cambridge/Addenbrooke’s Hospital(英国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Negative regulation of amino acid signaling by MAPK-regulated 4F2hc/Girdin complex2018

    • Author(s)
      Liang Weng , Yi-Peng Han, Atsushi Enomoto, Yasuyuki Kitaura, Shushi Nagamori, Yoshikatsu Kanai, Naoya Asai, Jian An, Maki Takagishi, Masato Asai, Shinji Mii, Takashi Masuko, Yoshiharu Shimomura, Masahide Takahashi.
    • Journal Title

      PLoS Biology

      Volume: 16 Issue: 3 Pages: e2005090-e2005090

    • DOI

      10.1371/journal.pbio.2005090

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Significance of perivascular tumour cells defined by CD109 expression in progression of glioma2017

    • Author(s)
      Shiraki Yukihiro、Mii Shinji、Enomoto Atsushi、Momota Hiroyuki、Han Yi-Peng、Kato Takuya、Ushida Kaori、Kato Akira、Asai Naoya、Murakumo Yoshiki、Aoki Kosuke、Suzuki Hiromichi、Ohka Fumiharu、Wakabayashi Toshihiko、Todo Tomoki、Ogawa Seishi、Natsume Atsushi、Takahashi Masahide
    • Journal Title

      The Journal of Pathology

      Volume: 243 Issue: 4 Pages: 468-480

    • DOI

      10.1002/path.4981

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Daple Coordinates Planar Polarized Microtubule Dynamics in Ependymal Cells and Contributes to Hydrocephalus2017

    • Author(s)
      Maki Takagishi, Masato Sawada, Shinya Ohata, Naoya Asai, Atsushi Enomoto, Kunihiko Takahashi, Liang Weng, Kaori Ushida, Hosne Ara, Shigeyuki Matsui, Kozo Kaibuchi,3Kazunobu Sawamoto, and Masahide Takahashi.
    • Journal Title

      Cell Reports

      Volume: 20 Issue: 4 Pages: 960-972

    • DOI

      10.1016/j.celrep.2017.06.089

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Significance of low mTORC1 activity in defining the characteristics of brain tumor stem cells.2017

    • Author(s)
      Han YP, Enomoto A, Shiraki Y, Wang SQ, Wang X, Toyokuni S, Asai N, Ushida K, Ara H, Ohka F, Wakabayashi T, Ma J, Natsume A, Takahashi M.
    • Journal Title

      Neuro Oncol

      Volume: 19 Pages: 636-647

    • DOI

      10.1093/neuonc/now237

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Tyrosine Phosphorylation of an Actin-Binding Protein Girdin Specifically Marks Tuft Cells in Human and Mouse Gut.2017

    • Author(s)
      Kuga D, Ushida K, Mii S, Enomoto A, Asai N, Nagino M, Takahashi M, Asai M.
    • Journal Title

      J Histochem Cytochem.

      Volume: 65(6) Issue: 6 Pages: 347-366

    • DOI

      10.1369/0022155417702586

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suppression of skin tumorigenesis in CD109-deficient mice.2016

    • Author(s)
      Sunagawa M, Mii S, Enomoto A, Kato T, Murakumo Y, Shiraki Y, Asai N, Asai M, Nagino M, Takahashi M.
    • Journal Title

      Oncotarget

      Volume: 7 Issue: 50 Pages: 82836-82850

    • DOI

      10.18632/oncotarget.12653

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Significance of low mTORC1 activity in defining the characteristics of brain tumor stem cells.2016

    • Author(s)
      Han YP, Enomoto A, Shiraki Y, Wang SQ, Wang X, Toyokuni S, Asai N, Ushida K, Ara H, Ohka F, Wakabayashi T, Ma J, Natsume A, Takahashi M.
    • Journal Title

      Neuro Oncol.

      Volume: -

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] CCDC88A mutations cause PEHO-like syndrome in humans and mouse.2016

    • Author(s)
      Nahorski MS, Asai M, Wakeling E, Parker A, Asai N, Canham N, Holder SE, Chen YC, Dyer J, Brady AF, Takahashi M, Woods CG.
    • Journal Title

      Brain.

      Volume: 139 Issue: 4 Pages: 1036-1044

    • DOI

      10.1093/brain/aww014

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Collective invasion of cancer: Perspectives from pathology and development2016

    • Author(s)
      Wang X, Enomoto A, Asai N, Kato T, Takahashi M
    • Journal Title

      Pathol Int

      Volume: 66 Issue: 4 Pages: 183-192

    • DOI

      10.1111/pin.12391

    • NAID

      120005893271

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Akt-dependent Girdin phosphorylation regulates repair processes after acute myocardial infarction.2015

    • Author(s)
      Hayano S, Takefuji M, Maeda K, Noda T, Ichimiya H, Kobayashi K, Enomoto A, Asai N, Takahashi M, Murohara T.
    • Journal Title

      J Mol Cell Cardiol.

      Volume: 88 Pages: 55-63

    • DOI

      10.1016/j.yjmcc.2015.09.012

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential involvement of kinesin-1 in the regulation of subcellular localization of Girdin2015

    • Author(s)
      Aya Muramatsu, Atsushi Enomoto, Takuya Kato, Liang Weng, Keisuke Kuroda, Naoya Asai, Masato Asai, Shinji Mii, Masahide Takahashia
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 463 Issue: 4 Pages: 999-1005

    • DOI

      10.1016/j.bbrc.2015.06.049

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Akt-Girdin as oncotarget.2015

    • Author(s)
      Takahashi M, Asai N, Enomoto A.
    • Journal Title

      Oncoscience.

      Volume: 2(10) Pages: 811-812

    • Related Report
      2015 Research-status Report
  • [Remarks] 腫瘍病理学/神経機能病理学(病理学第二) 独自ホームページ

    • URL

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

    • Related Report
      2016 Research-status Report
  • [Remarks] 名古屋大学医学部・大学院医学系研究科 腫瘍病理学・分子病理学分野

    • URL

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

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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