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Live-cell 3D imaging analysis of the dynamics of epithelial cells and functional molecules in epithelial tubular formation

Planned Research

Project AreaRegulation of polarity signaling during morphogenesis, remodeling, and breakdown of epithelial tubular structure
Project/Area Number 23112005
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTohoku University

Principal Investigator

Ohashi Kazumasa  東北大学, 生命科学研究科, 准教授 (10312539)

Project Period (FY) 2011-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥95,030,000 (Direct Cost: ¥73,100,000、Indirect Cost: ¥21,930,000)
Fiscal Year 2015: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2014: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2013: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2012: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2011: ¥23,010,000 (Direct Cost: ¥17,700,000、Indirect Cost: ¥5,310,000)
Keywords上皮細胞 / 上皮管腔組織 / アクチン骨格 / RhoGEF / Rho / メカノシグナル / イメージング / 機械的シグナル / GEF / 管腔形成 / コフィリン
Outline of Final Research Achievements

In this study, we investigated the roles of Rho-GEFs, Farp1 and Solo, which are involved in mechanoresponses, in the ordering and the tubule formation of epithelial cells. We found that Farp1 facilitates the adhesion-dependent growth of mammary epithelial cell through integrins. We found that Solo binds to a simple epithelium-specific intermediate filament, keratin8 and keratin18, and Solo is required to organize and maintain of the keratin8/18 network in epithelial cells. We also showed that Solo is required to activate RhoA and to generate the resistance force in response to tensile-force application. Furthermore, we showed that knockdown of Solo accelerates the velocity of collective cell migration of MDCK cells, and enlarges the lumen area of HGF-induced tubule of 3D-cultured MDCK cells.

Report

(6 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (51 results)

All 2016 2015 2014 2013 2012 2011 Other

All Journal Article (15 results) (of which Peer Reviewed: 14 results,  Acknowledgement Compliant: 4 results,  Open Access: 1 results) Presentation (31 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Book (1 results) Remarks (4 results)

  • [Journal Article] Interplay between Solo and keratin filaments is crucial for force-induced stress fiber reinforcement.2016

    • Author(s)
      Fujiwara, S., Ohashi, K., T. Mashiko, Kondo, H., Mizuno, K.
    • Journal Title

      Mol. Biol. Cell

      Volume: 27 Issue: 6 Pages: 954-966

    • DOI

      10.1091/mbc.e15-06-0417

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Rho-guanine nucleotide exchange factors involved in cyclic stretch-induced reorientation of vascular endothelial cells2015

    • Author(s)
      Hiyori Abiko*, Sachiko Fujiwara*, Kazumasa Ohashi, Ryuichi Hiatari, Toshiya Mashiko, Naoya Sakamoto, Masaaki Sato, Kensaku Mizuno (* co-first authors)
    • Journal Title

      Journal of Cell Science

      Volume: 印刷中 Pages: 1683-1695

    • DOI

      10.1242/jcs.157503

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles of cofilin in development and its mechanisms of regulation.2015

    • Author(s)
      Ohashi, K.
    • Journal Title

      Develop. Growth Differ.

      Volume: 57 Issue: 4 Pages: 275-290

    • DOI

      10.1111/dgd.12213

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Rho-guanine nucleotide exchange factors involved in cyclic stretch-induced reorientation of vascular endothelial cells.2015

    • Author(s)
      Abiko, H., Fujiwara, S., Ohashi, K., Hiatari, R., Mashiko, T., Sakamoto, N., Sato, M., and Mizuno, K.
    • Journal Title

      J. Cell Sci.

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Insulin receptor substrate-4 binds to slingshot-1 phosphatase and promotes cofilin dephosphorylation.2014

    • Author(s)
      Homma Y, Kanno S, Sasaki K, Nishita M, Yasui A, Asano T, Ohashi K, Mizuno K.
    • Journal Title

      J Biol Chem.

      Volume: 289 Issue: 38 Pages: 26302-26313

    • DOI

      10.1074/jbc.m114.565945

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Damnacanthal, an effective inhibitor of LIM-kinase, inhibits cell migration and invasion.2014

    • Author(s)
      Ohashi, K.
    • Journal Title

      Mol. Biol. Cell

      Volume: 25 Issue: 6 Pages: 828-840

    • DOI

      10.1091/mbc.e13-09-0540

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] p63RhoGEF-mediated formation of a single polarized lamellipodium is required for chemotactic migration in breast carcinoma cells2013

    • Author(s)
      Hayashi, A., Hiatari, R., Tsuji, T., Ohashi, K., Mizuno, K.
    • Journal Title

      FEBS Lett

      Volume: 587 Issue: 6 Pages: 698-705

    • DOI

      10.1016/j.febslet.2013.01.043

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CaMKIIβ-mediated LIM-kinase activation plays a crucial role in BDNF-induced neuritogenesis2013

    • Author(s)
      Saito, A., Miyajima, K., Akatsuka, J., Kondo, H., Mashiko, T., Kiuchi, T., Ohashi, K.,Mizuno, K.
    • Journal Title

      Genes Cells

      Volume: (in press) Issue: 7 Pages: 533-543

    • DOI

      10.1111/gtc.12054

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coactosin accelerates cell dynamism by promoting actin polymerization2013

    • Author(s)
      Xubin Hou
    • Journal Title

      Dev. Biol.

      Volume: in press

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytochalasin D acts as an inhibitor of the actin-cofilin interaction.2012

    • Author(s)
      Kazuyasu Shoji
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 424 Issue: 1 Pages: 52-57

    • DOI

      10.1016/j.bbrc.2012.06.063

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Furry Protein Promotes Aurora A-mediated Polo-like Kinase 1 Activation2012

    • Author(s)
      Ikeda, M., Chiba, S., Ohashi, K., Mizuno, K.
    • Journal Title

      J. Biol. Chem

      Volume: 287 Issue: 33 Pages: 27670-27681

    • DOI

      10.1074/jbc.m112.378968

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Wntの細胞内平面極性シグナルによるRhoファミリーの活性化とアクチン細胞骨格制御機構2012

    • Author(s)
      大橋一正
    • Journal Title

      生体の科学

      Volume: 63 Pages: 177-182

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Visualization of cofilin-actin and Ras-Raf interactions by bimolecular fluorescence complementation assays using a new pair of split Venus fragments2012

    • Author(s)
      K.Ohashi
    • Journal Title

      Biotechniques

      Volume: 52 Issue: 1 Pages: 45-50

    • DOI

      10.2144/000113777

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Live-cell imaging of G-actin dynamics using sequential FDAP2011

    • Author(s)
      Kiuchi, T, et al
    • Journal Title

      BioArchitecture

      Volume: 1 Pages: 1-5

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LIM-kinase- mediated cofilin phosphorylation decelerates actin retrograde flow in lamellipodia2011

    • Author(s)
      K. Ohashi, S. Fujiwara, T. Watanabe, T. Kiuchi, M. Sato, K. Mizuno
    • Journal Title

      J. Biol. Chem.

      Volume: Vol. 286 Issue: 42 Pages: 36340-36351

    • DOI

      10.1074/jbc.m111.259135

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] メカノストレス応答に寄与するRhoGEF, Soloの上皮細胞集団の秩序化における機能2016

    • Author(s)
      大橋一正、藤原佐知子、酒井高輝、安彦日和、近藤洋志、増子寿弥、水野健作
    • Organizer
      2016年 生体運動合同班会議プログラム
    • Place of Presentation
      キャンパスプラザ京都 5階第一講義室(京都府・京都市)
    • Year and Date
      2016-01-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Rho-GEF Soloによる細胞骨格の制御と力覚応答における機能2015

    • Author(s)
      藤原佐知子、安彦日和、大橋一正、増子寿弥、近藤洋志、佐藤正明、水野健作
    • Organizer
      第38回日本分子生物学会年会 第88回日本生化学大会
    • Place of Presentation
      神戸ポートアイランド(兵庫県・神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] The role of Solo, a Rho-GEF involved in mechanotransduction, in the dynamical ordering of epithelial cell populations2015

    • Author(s)
      大橋一正
    • Organizer
      The Second International Meeting for Epithelial Tubulology
    • Place of Presentation
      北海道大学医学部 学友会館フラテホール(北海道・札幌市)
    • Year and Date
      2015-08-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] RhoA/RhoC特異的GEFであるSoloの力覚応答における役割2015

    • Author(s)
      大橋一正、藤原佐知子、増子寿弥、安彦日和、佐藤正明、水野健作
    • Organizer
      第67回日本細胞生物学会
    • Place of Presentation
      タワーホール船堀(東京都・江戸川区)
    • Year and Date
      2015-06-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] Rho-GEF Soloによるアクチン繊維と中間径フィラメントの制御とメカノセンシングにおける機能2015

    • Author(s)
      藤原佐知子、安彦日和、大橋一正、増子寿弥、水野健作
    • Organizer
      日本生化学会東北支部 第81回例会・シンポジウム
    • Place of Presentation
      東北大学さくらホール(宮城県・仙台市)
    • Year and Date
      2015-05-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] Identification and functional analysis of Rho-GEFs involved in cyclic stretch-induced cell orientation of vascular endothelial cells2014

    • Author(s)
      Toshiya Mashiko, Sachiko Fujiwara, Hiroshi Kondo, Hiyori Abiko, Masaaki Sato, Kazumasa Ohashi, Kensaku Mizuno
    • Organizer
      第37回日本分子生物学会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] ゲルゾリンはアクチンオリゴマーによるスリングショットの活性化を介してコフィリンの脱リン酸化を亢進する2014

    • Author(s)
      高橋克宣、菅野新一郎、大橋一正、水野健作
    • Organizer
      第87回日本生化学大会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Farp1はインテグリンを介した細胞接着に関与する2014

    • Author(s)
      梶 紀子, 萱場 敦子, 高橋 将太, 大橋 一正, 水野 健作
    • Organizer
      第66回日本細胞生物学会
    • Place of Presentation
      奈良
    • Year and Date
      2014-06-11 – 2014-06-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] Identification and characterization of Solo as a Rho-GEF involved in mechanosensing2014

    • Author(s)
      Sachiko Fujiwara, Toshiya Mashiko, Hiroshi Kondo, Hiyori Abiko, Masaaki Sato, Kazumasa Ohashi, Kensaku Mizuno
    • Organizer
      International Symposium on Mechanobiology
    • Place of Presentation
      岡山
    • Year and Date
      2014-05-20 – 2014-05-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] Identification of Rho-GEFs involved in mechano-biological responses of vascular endothelial cells.2013

    • Author(s)
      Kazumasa Ohashi
    • Organizer
      International Symposium on Biomedical Engineering Interface
    • Place of Presentation
      仙台
    • Year and Date
      2013-03-14
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] メカノセンシングに関与するRho-GEFとして同定したSOLO の機能解析2013

    • Author(s)
      藤原佐知子
    • Organizer
      日本生化学会東北支部第79回例会
    • Place of Presentation
      仙台
    • Related Report
      2013 Annual Research Report
  • [Presentation] 乳がん組織の極性移動にはp63RhoGEFによるラメリポディア形成の極性化が必要である2013

    • Author(s)
      大橋一正
    • Organizer
      第65回日本細胞生物学会大会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Annual Research Report
  • [Presentation] Farp1 is involved in ECM stiffness-induced transformation of mammary epithelial cells.2013

    • Author(s)
      Kaji, N.
    • Organizer
      第65回日本細胞生物学会大会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] p63RhoGEF is required for chemotactic migration of breast carcinoma cells by forming a single polarized lamellipodium.2013

    • Author(s)
      Ohashi, K.
    • Organizer
      第65回日本細胞生物学会大会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Annual Research Report
  • [Presentation] 細胞の力覚応答に関与するRho-GEFの同定と機能2013

    • Author(s)
      水野健作
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 細胞の力覚応答に関わるRho-GEF として同定したSolo の機能解析2013

    • Author(s)
      藤原 佐知子
    • Organizer
      第36回日本分子生物学会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] 細胞外基質の硬さ依存的な乳腺上皮細胞の形質転換におけるFarp1の機能2013

    • Author(s)
      高橋 将太
    • Organizer
      第36回日本分子生物学会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
  • [Presentation] DblファミリーRho-GEFであるCDEPは乳腺上皮細胞の細胞外マトリックスの硬さ依存的な形質転換に関与する2012

    • Author(s)
      高橋将太
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-14
    • Related Report
      2012 Annual Research Report
  • [Presentation] Furry is a positive regulator of microtubule acetylation in mitotic spindle.2012

    • Author(s)
      Tomoaki Nagai
    • Organizer
      第52回American Society for Cell Biology Annual Meeting
    • Place of Presentation
      サンフランシスコ、米国
    • Year and Date
      2012-12-13
    • Related Report
      2012 Annual Research Report
  • [Presentation] The Regulation of the Organ Morphology Via Cytoskeletal Remodeoing.2012

    • Author(s)
      Ritsuko Morita
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-11
    • Related Report
      2012 Annual Research Report
  • [Presentation] Identification of Rho-GEFs Involved in Cyclic Stretch-induced Mechanosensing of Vascular Endothelial Cells.2012

    • Author(s)
      Hiroshi Kondo
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-11
    • Related Report
      2012 Annual Research Report
  • [Presentation] Identification of Rho-GEFs involved in mechanosensing of vascular endothelial cells.2012

    • Author(s)
      Hiroshi Kondo
    • Organizer
      第45回日本発生生物学会・第64回日本細胞生物学会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2012-05-28
    • Related Report
      2012 Annual Research Report
  • [Presentation] Identification of cytochalasin D as an inhibitor of actin-cofilin in teraction2011

    • Author(s)
      東海林和康, 他
    • Organizer
      第34回日本分子生物学会
    • Place of Presentation
      横浜,パシフィコ横浜
    • Year and Date
      2011-12-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] Furry is involved in bipolar spindle formation through Plk1 activation2011

    • Author(s)
      池田真教, 他
    • Organizer
      第34回日本分子生物学会
    • Place of Presentation
      横浜,パシフィコ横浜
    • Year and Date
      2011-12-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Identification of Rho-GEFs involved in breast cancer cell migration2011

    • Author(s)
      日當竜一, 他
    • Organizer
      第34回日本分子生物学会
    • Place of Presentation
      横浜,パシフィコ横浜
    • Year and Date
      2011-12-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Activation of LIMK1 by CaMKIIb is required for BDNF-induced dendritogenesis in rat cortical neurons2011

    • Author(s)
      北谷佳那恵, 他
    • Organizer
      第34回日本分子生物学会
    • Place of Presentation
      横浜,パシフィコ横浜
    • Year and Date
      2011-12-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Phosphorylation and activation of LIMK1 by CaMKIIbeta in BDNF-induced dendritogenesis2011

    • Author(s)
      大橋一正, 他
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都,国立京都国際会館
    • Year and Date
      2011-09-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] Regulation of Slingshot-1 phosphorylation in SDF-1-induced T cell chemotaxis2011

    • Author(s)
      川村友理子, 他
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都,国立京都国際会館
    • Year and Date
      2011-09-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] Identification and functional roles of Rho-GEFs that are involved in cell migration2011

    • Author(s)
      林文, 他
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都,国立京都国際会館
    • Year and Date
      2011-09-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] Activation of LIMK1 by CaMKIIb is required for BDNF-induced dendritogenesis in rat cortical neurons2011

    • Author(s)
      大橋一正, 他
    • Organizer
      第63回日本細胞生物学会大会
    • Place of Presentation
      札幌,北海道大学
    • Year and Date
      2011-06-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] Multipoit measurements of fluorescence decay after photoactivation of Dronpa-actin reveal spatial distribution of G-actin concentration between lamellipodium and cell body2011

    • Author(s)
      木内泰, 他
    • Organizer
      第63回日本細胞生物学会大会
    • Place of Presentation
      札幌,北海道大学
    • Year and Date
      2011-06-28
    • Related Report
      2011 Annual Research Report
  • [Book] Methods in Molecular Biology, Exocytosis and Endocytosis Second edition2014

    • Author(s)
      Ohashi, K., and Mizuno, K.
    • Total Pages
      16
    • Publisher
      Springer Press
    • Related Report
      2014 Annual Research Report
  • [Remarks] 東北大学 大学院生命科学研究科 情報伝達分子解析分野 水野研究室

    • URL

      http://www.biology.tohoku.ac.jp/lab-www/mizuno_lab/

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
  • [Remarks] 東北大学 大学院生命科学研究科 情報伝達分子解析分野 水野研究室

    • URL

      http://www.biology.tohoku.ac.jp/lab-www/mizuno_lab/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 東北大学 水野研(情報伝達分子解析分野)

    • URL

      http://www.biology.tohoku.ac.jp/lab-www/mizuno_lab/

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.biology.tohoku.ac.jp/lab-www/mizuno_lab/

    • Related Report
      2011 Annual Research Report

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Published: 2011-08-01   Modified: 2019-07-29  

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