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2013 Fiscal Year Final Research Report

The role of Rho-mDia siganling in tissue architecture and homeostasis in the body

Research Project

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Project/Area Number 23229003
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionKyoto University

Principal Investigator

NARUMIYA Shuh  京都大学, 医学(系)研究科(研究院), 教授(特任) (70144350)

Project Period (FY) 2011-05-31 – 2014-03-31
KeywordsmDia / actin / Liprin / neuroepithelial polarity / neuronal migration / axon guidance / cytokinesis / tissue architecture
Research Abstract

Here we examined action and regulation of mDia, a Rho-regulated actin nucleator/polymerization factor, at the molecular and cellular level and the role of each mDia isoform in tissue architecture and maintenance in the body. In the former, we discovered that mDia catalyzes actin polymerization by rotating along the pitch of actin filament and that Liprin-alpha negatively regulating mDia activity by trapping mDia in the cytosol. In the latter, we used mDia-deficient KO mice and discovered that mDia contribute to shaping and maintenance of architecture of the brain by regulating the neuroepithelial polarity, tangential migration of inhibitory neuron precursors and axon guidance of the corticospinal tract neurons. We also discovered that mDia2 regulates cytokinesis of erythroblasts and contributes to maintenace of the hematopoietic system. In this work, we further elucidated how mDia-induced actin cytoskeleton functions in each of these in vivo processes.

  • Research Products

    (35 results)

All 2013 2012 2011 Other

All Journal Article (10 results) Presentation (24 results) (of which Invited: 8 results) Book (1 results)

  • [Journal Article] Loss of a Rho-Regulated Actin Nucleator, mDia2, Impairs Cytokinesis during Mouse Fetal Erythropoiesis2013

    • Author(s)
      Watanabe S, De Zan T, Ishizaki T, Yasuda S, Kamijo H, Yamada D, Aoki T, Kiyonari H, Kaneko H, Shimizu R, Yamamoto M, Goshima G, Narumiya S
    • Journal Title

      Cell Rep

      Volume: 5(4) Pages: 926-932

    • DOI

      10.1016/j.celrep.2013.10.021

  • [Journal Article] Physiological roles of Rho and Rho effectors in mammals2013

    • Author(s)
      Thumkeo D,Watanabe S, Narumiya S
    • Journal Title

      Eur J Cell Biol

      Volume: 92(10-11) Pages: 303-315

    • DOI

      10.1016/j.ejcb.2013.09.002

  • [Journal Article] EphA4-dependent axon retraction and midline localization of Ephrin-B3 are disrupted in the spinal cord of mice lacking mDia1 and mDia3 in combination2013

    • Author(s)
      Toyoda Y, Shinohara R, Thumkeo D, Kamijo H, Nishimaru H, Hioki H, Kaneko T, Ishizaki T, Furuyashiki T, Narumiya S
    • Journal Title

      Genes Cells

      Volume: 18(10) Pages: 873-885

    • DOI

      10.1111/gtc.12081

  • [Journal Article] F and G-actin homeostasis regulates mechanosensitive actin nucleation by formins2013

    • Author(s)
      Higashida C, Kiuchi T, Akiba Y, Mizuno H, Maruoka M, Narumiya S, Mizuno K, Watanabe N
    • Journal Title

      Nature Cell Biol

      Volume: 15(4) Pages: 395-405

    • DOI

      10.1038/ncb2693

  • [Journal Article] Citron-kinase mediates transition from constriction to abscission through its coiled-coil domain2013

    • Author(s)
      Watanabe S, De Zan T, Ishizaki T, Narumiya S
    • Journal Title

      J . Cell Sci.

      Volume: 126(Pt 8) Pages: 1773-1784

    • DOI

      10.1242/jcs.116608

  • [Journal Article] A new role of multi scaffold protein Liprin- α : Liprin- α suppresses Rho-mDia mediated stress fiber formation2012

    • Author(s)
      Sakamoto S, Narumiya S, Ishizaki T
    • Journal Title

      Bioarchitecture

      Volume: 2(2) Pages: 43-49

    • DOI

      10.4161/bioa.20422

  • [Journal Article] A role for mDia, a Rho-regulated actin nucleator, in tangential migration of interneuron precursors2012

    • Author(s)
      Shinohara R, Thumkeo D, Kamijo H, Kaneko N, Sawamoto K, Watanabe K, Takebayashi H, Kiyonari H, Ishizaki T, Furuyashiki T, Narumiya S
    • Journal Title

      Nature Neurosci

      Volume: 15(3) Pages: 373 -380

    • DOI

      10.1038/nn3020

  • [Journal Article] Liprin- α controls stress fiber formation by binding to mDia and regulating its membrane localization2012

    • Author(s)
      Sakamoto S, Ishizaki T, Okawa K, Watanabe S, Arakawa T, Watanabe N, Narumiya S
    • Journal Title

      Cell Sci

      Volume: 125(1) Pages: 108-120

    • DOI

      10.1242/jsc.087411

  • [Journal Article] Deficiency of mDia, an actin nucleator, disrupts integrity of neuroepithelium and causes periventricular dysplasia2011

    • Author(s)
      Thumkeo D, Shinohara R, Watanabe K, Takebayashi H, Toyoda Y, Tohyama K, Ishizaki T, Furuyashiki T, Narumiya S
    • Journal Title

      PLoS One

      Volume: 6(9) Pages: e25465

    • DOI

      101371/journal.pene.0025465

  • [Journal Article] Impaired vascular remodeling in the yolk sac of embryos deficient in ROCK-I and ROCK-II2011

    • Author(s)
      Kamijo H, Matsumura Y, Thumkeo D, Koike S, Masu M, Shimizu Y, Ishizaki T, Narumiya S
    • Journal Title

      Genes Cells

      Volume: 16(10) Pages: 1012-1021

    • DOI

      10.1111/j.1365-2443.2011.01546.x

  • [Presentation] アクチン重合分子mDia2 によるマウス発生期の赤芽球細胞質分裂の調節2013

    • Author(s)
      Watanabe S., et al
    • Organizer
      第65回細胞生物学会大会
    • Place of Presentation
      名古屋
    • Year and Date
      2013-06-21
  • [Presentation] Rho-mDia pathway in the cell, the tissue and the body2012

    • Author(s)
      Narumiya, S
    • Organizer
      The 2012 Cold Spring Harbor Asia Conference on "Small GTPases at Different Scales : proteins, membranes, cells"
    • Place of Presentation
      Suzhou, China
    • Year and Date
      20120924-28
    • Invited
  • [Presentation] Rho-mDia signaling; regulation and actions in cells and tissues2012

    • Author(s)
      Narumiya, S
    • Organizer
      The 2nd Internaitonal Meeting of the German Society for Cell Biology on "Actin Dynamics"
    • Place of Presentation
      Regensburg, Germany
    • Year and Date
      20120912-15
    • Invited
  • [Presentation] Rho-mediated regulation of actin cytoskeleton; from single molecule actions to significance in the body. Plenary Lecture2011

    • Author(s)
      Narumiya, S
    • Organizer
      The 84th Annual Meeting of the Japanese Biochemical Society
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      20110921-24
    • Invited
  • [Presentation] Phenotype analysis of mDia-deficient mice; impaired neurblast migration and disordered proliferaitotn of neural stem cells2011

    • Author(s)
      Narumiya, S
    • Organizer
      Gordon Research Conference on Mechanism of Cell Signaling
    • Place of Presentation
      Maine, U.S.A.
    • Year and Date
      2011-08-01
    • Invited
  • [Presentation] 毒素研究から細胞生物学へ : Rho 研究の冒険

    • Author(s)
      成宮周
    • Organizer
      第152回日本獣医学会学術集会
    • Place of Presentation
      大阪
  • [Presentation] My Adventures in Medical Research; Prostanoid Receptors and Rho GTPase

    • Author(s)
      Narumiya, S
    • Organizer
      The 89th Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      Matsumoto, Japan
    • Invited
  • [Presentation] Liprin-alpha suppresses Rho-mDia mediated stress fiber formation

    • Author(s)
      Ishizaki, T
    • Organizer
      Cold Spring Harbor Asia meeting on Small GTPases at Different Scales : Proteins, Membranes, Cells
    • Place of Presentation
      Suzhou, China
    • Invited
  • [Presentation] Roles of mDia in TCR signaling and its potential as a novel target for immunoregualtion drugs

    • Author(s)
      Dean, T, Watanabe, S., and Narumiya, S
    • Organizer
      The 2nd International Conference in Medicine and Public Health
    • Place of Presentation
      Bangkok, Thailand
    • Invited
  • [Presentation] Rho-mDia signaling in developing nervous system

    • Author(s)
      Dean, T, Shinohara, R. and Narumiya, S
    • Organizer
      The 84th Annual Meeting of the Japanese Pharmacological Society
    • Place of Presentation
      Yokohama, Japan
    • Invited
  • [Presentation] Actin nucleator mDia1 and mDia3, cooperatively function in T cell receptor signaling-dependent T cell development in thymus

    • Author(s)
      Dean T., et al
    • Organizer
      The 87th Annual Meeting of the Japanese Pharmacological Society
    • Place of Presentation
      Sendai, Japan
  • [Presentation] Physiological roles of mDia, a Rho effector and actin nucleator, in mammals

    • Author(s)
      Dean T., et al
    • Organizer
      The 86th Annual Meeting of the Japanese Biochemistry Society
    • Place of Presentation
      Yokohama, Japan
  • [Presentation] Roles of mDia, a Rho effector and formin family actin-nucleator, in T cell development

    • Author(s)
      Dean T., et al
    • Organizer
      The 86th Annual Meeting of the Japanese Pharmacological Society
    • Place of Presentation
      Fukuoka, Japan
  • [Presentation] Roles of mDia, a Rho effector and actin nucleator, in neuroepithelium integrity and neuroblast migration

    • Author(s)
      Dean T., et al
    • Organizer
      The 64th Annual Meeting of the Japanese Society for Cell Biology
    • Place of Presentation
      Kobe, Japan
  • [Presentation] Deficiency of mDia, an actin nucleator, disrupts integrity of neuroepithelium and causes periventricular dysplasia

    • Author(s)
      Dean T., et al
    • Organizer
      Cancer Workshop for Young Scientists
    • Place of Presentation
      Nagano, Japan
  • [Presentation] Disruption of neuroepithelial integrity by mDia deficiency causes periventricular heterotopia and hydrocephalus

    • Author(s)
      Dean T., et al
    • Organizer
      The 63th Annual Meeting of the Japanese Society for Cell Biology
    • Place of Presentation
      Sapporo, Japan
  • [Presentation] Loss of a Rho-regulated actin nucleator, mDia2, impairs cytokinesis during fetal erythropoiesis

    • Author(s)
      Watanabe S., et al
    • Organizer
      The 61th NIBB Conference
    • Place of Presentation
      Okazaki, Japan
  • [Presentation] 生体内におけるmDia の機能解析

    • Author(s)
      Watanabe S., et al
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      Yokohama, Japan
  • [Presentation] 配偶子形成および受精におけるRho 標的タンパク質mDia の役割

    • Author(s)
      Watanabe S., et al
    • Organizer
      第59回日本実験動物学会総会
    • Place of Presentation
      Beppu, Japan
  • [Presentation] Citron-kinase mediates transition from constriction to abscission through its coiled-coil domain

    • Author(s)
      Watanabe S., et al
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      Fukuoka, Japan
  • [Presentation] Roles of mDia2, an actin nucleator, in embryonic development

    • Author(s)
      Watanabe S., et al
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      Fukuoka, Japan
  • [Presentation] A role for mDia, a Rho-regulated actin nucleator, in emotionalchanges induced by social isolation stress

    • Author(s)
      Deguchi, Y., et al
    • Organizer
      Nauro 2013
    • Place of Presentation
      Kyoto, Japan
  • [Presentation] A role for mDia, a Rho-regulated actin nucleator, in elevated anxiety induced by social isolation stress in mice

    • Author(s)
      Deguchi, Y., et al
    • Organizer
      第87回日本薬理学会年会
  • [Presentation] 配偶子形成および受精におけるRho 標的タンパク質mDia の役割

    • Author(s)
      Sakamoto, S., et al
    • Organizer
      日本実験動物科学・技術九州2012
    • Place of Presentation
      Beppu, Japan
  • [Book] Molecular Structures, Cellular Functions and Physiological Roles of Rho Effectors in Ras superfamily small G proteins : Biology and Mechanisms (Wittinghofer, A., ed.)

    • Author(s)
      Ishizaki T., Narumiya, S
    • Publisher
      Springer(in press)

URL: 

Published: 2015-06-25  

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