Regulation mechanisms of mechanostress-induced actin cytoskeleton reorganzation

• Project/Area Number: 22616001
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Mechanobiology
• Research Institution: Tohoku University
• Principal Investigator: OHASHI Kazumasa 東北大学, 大学院・生命科学研究科, 准教授 (10312539)
• Co-Investigator(Renkei-kenkyūsha): SAKAMOTO Naoya 川崎医療福祉大学, 医療技術学部, 准教授 (20361115)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: アクチン骨格 / Rho-GEF / メカノセンシング / 血管内皮細胞 / 乳腺上皮細胞 / Rhoファミリー / Dblファミリー / 細胞外基質 / Db1ファミリー

Research Abstract

In this study, we investigated the molecular mechanisms of mechanostress-induced actin cytoskeleton remodeling. We succeeded in identifying 8Rho-GEFs involved in cyclic stretch-induced cell alignment of vascular endothelial cells and 5 Rho-GEFs involved in the rigidity of extracellular matrix-induced epithelial-mesenchymal transition (EMT) -like transformation in mammary epithelial cells. We also revealed that p63RhoGEF is plays a crucial role in the polarized cell migration.

Research Products

• [Journal Article] CaMKIIβ-mediated LIM-kinase activation plays a crucial role in BDNF-induced neuritogenesis (2013)
  • 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
  • Peer Reviewed
• [Journal Article] p63RhoGEF-mediated formation of a single polarized lamellipodium is required for chemotactic migration in breast carcinoma cells (2013)
  • 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
  • Peer Reviewed
• [Journal Article] Coactosin accelerates cell dynamism by promoting actin polymerization (2013)
  • Author(s): Xubin Hou
  • Journal Title: Dev. Biol. Volume: in press
  • Peer Reviewed
• [Journal Article] Furry Protein Promotes Aurora A-mediated Polo-like Kinase 1 Activation (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Visualization of cofilin-actin and Ras-Raf interactions by bimolecular fluorescence complementation assays using a new pair of split Venus fragments (2012)
  • Author(s): K.Ohashi
  • Journal Title: Biotechniques Volume: 52 Issue: 1 Pages: 45-50
  • DOI: 10.2144/000113777
  • Peer Reviewed
• [Journal Article] Role of nesprin-1 in nuclear deformation in endothelial cells under static and uniaxial stretching conditions (2012)
  • Author(s): T. Anno, N. Sakamoto, M. Sato
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: Vol. 424 Issue: 1 Pages: 94-99
  • DOI: 10.1016/j.bbrc.2012.06.073
  • Peer Reviewed
• [Journal Article] Role of paxillin in the early phase of orientation of the vascular endothelial cells exposed to cyclic stretching (2012)
  • Author(s): Huang, W., Sakamoto, N., Miyazawa, M.R., Sato, M.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 418 Issue: 4 Pages: 708-713
  • DOI: 10.1016/j.bbrc.2012.01.083
  • 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、辻拓史、水野健作
  • Journal Title: 生体の科学 Volume: 63巻3号 Pages: 177-182
• [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
  • 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
• [Journal Article] LIM-kinase- mediated cofilin phosphorylation decelerates actin retrograde flow in lamellipodia (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Measurements of spatiotemporal changes in G-actin concentration reveal its effect on stimulus-induced actin assembly and lamellipodium extension (2011)
  • Author(s): T.Kiuchi, T.Nagai, K.Ohashi, K.Mizuno
  • Journal Title: The Journal of Cell Biology Volume: 193(2) Issue: 2 Pages: 365-380
  • DOI: 10.1083/jcb.201101035
  • Peer Reviewed
• [Journal Article] Development of an endothelial-smooth muscle cell coculture model using phenotype-controlled smooth muscle cells (2011)
  • Author(s): N.Sakamoto
  • Journal Title: Annals of Biomedical Engineering Volume: 39 Issue: 11 Pages: 2750-2758
  • DOI: 10.1007/s10439-011-0372-8
  • Peer Reviewed
• [Journal Article] Combined stimulation with cyclic stretching and hypoxia increases production of matrix metalloproteinase-9 and cytokines by macrophages (2011)
  • Author(s): K.Oya
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 412 Issue: 4 Pages: 678-682
  • DOI: 10.1016/j.bbrc.2011.08.024
  • Peer Reviewed
• [Journal Article] Live-cell imaging of G-actin dynamics using sequential FDAP (2011)
  • Author(s): Kiuchi, T, et al
  • Journal Title: BioArchitecture Volume: 1 Pages: 1-5
  • Peer Reviewed
• [Journal Article] Measurements of spatiotemporal changes in G-actin concentration reveal its effect on stimulus-induced actin assembly and lamellipodium extension (2011)
  • Author(s): Kiuchi T., et al
  • Journal Title: J.Cell Biol. Volume: 193 Pages: 365-380
  • Peer Reviewed
• [Journal Article] Involvement of p114-RhoGEF and Lfc in Wnt-3a- and Dishevelled-induced RhoA activation and neurite retraction in N1E-115 mouse neuroblastoma cells (2010)
  • Author(s): Tsuji, T., Ohta,Y., Kanno, Y., Hirose, K., Ohashi, K., Mizuno, K.
  • Journal Title: Mol. Biol. Cell Volume: 21 Issue: 20 Pages: 3590-3600
  • DOI: 10.1091/mbc.e10-02-0095
  • Peer Reviewed
• [Journal Article] LIM-kinase is critical for the mesenchymal-to-amoeboid cell morphological transition in 3D matrices (2010)
  • Author(s): Mishima, T., Naotsuka, M., Horita, Y., Sato, M., Ohashi, K., Mizuno, K.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 392 Issue: 4 Pages: 577-581
  • DOI: 10.1016/j.bbrc.2010.01.075
  • Peer Reviewed
• [Journal Article] Involvement of p114-RhoGEF and Lfc in Wnt-3a-and Dishevelled-induced RhoA activation and neurite retraction in N1E-115 mouse neuroblastoma cells (2010)
  • Author(s): Tsuji T., et al
  • Journal Title: Mol.Biol.Cell Volume: 21 Pages: 3590-3600
  • Peer Reviewed
• [Presentation] Identification of Rho-GEFs involved in mechano-biological responses of vascular endothelial cells (2013)
  • Author(s): Ohashi K., Abiko H., Kondo H., Fujiwara S., Mashiko K., Sakamoto N., Sato M., Mizuno K.
  • Organizer: International Symposium on Biomedical Engineering Interface
  • Place of Presentation: 仙台
• [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
  • Invited
• [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、大橋一正、北谷佳那恵、直塚萌、佐藤圭一、阿部彰子、萱場敦子、梶紀子、水野健作
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] Identification of Rho-GEFs Involved in Cyclic Stretch-induced Mechanosensing of Vascular Endothelial Cells (2012)
  • Author(s): Kondo, H., Ohashi, K., Abiko, H., Hiatari, R., Sakamoto, N., Sato, M., Mizuno, K.
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡
• [Presentation] Identification of Rho-GEFs involved in mechanosensing of vascular endothelial cells (2012)
  • Author(s): Kondo, H., Ohashi, K., Abiko, H., Hiatari, R., Sakamoto, N., Sato, M., Mizuno, K.
  • 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
• [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
• [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
• [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
• [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
• [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
• [Presentation] Identification of cytochalasin D as an inhibitor of actin-cofilin in teraction (2011)
  • 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
• [Presentation] Identification of cytochalasin D as an inhibitor of actin-cofilin interaction (2011)
  • 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
• [Presentation] Furry is involved in bipolar spindle formation through Plk1 activation (2011)
  • 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
• [Presentation] Identification of Rho-GEFs involved in breast cancer cell migration (2011)
  • 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
• [Presentation] Activation of LIMK1 by CaMKIIb is required for BDNF-induced dendritogenesis in rat cortical neurons (2011)
  • 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
• [Presentation] Phosphorylation and activation of LIMK1 by CaMKIIbeta in BD NF-induced dendritogenesis (2011)
  • 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
• [Presentation] Regulation of Slingshot-1 phosphorylation in SDF-1-induced T cell chemotaxis (2011)
  • 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
• [Presentation] Identification and functional roles of Rho-GEFs that are involved in cell migration (2011)
  • 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
• [Presentation] Phosphorylation and activation of LIMK1 by CaMKIIbeta in BDNF-induced dendritogenesis (2011)
  • 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
• [Presentation] Activation of LIMK1 by CaMKIIb is required for BDNF-induced dendritogenesis in rat cortical neurons (2011)
  • 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
• [Presentation] Multipoit measurements of fluorescence decay after photoactivation of Dronpa-actin reveal spatial distribution of G-actin concentration between lamellipodium and cell body (2011)
  • 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
• [Presentation] Identification of Rho-GEFs involved in ECM rigidity-induced transformation of mammary epithelial cells (2011)
  • Author(s): Kitatani, K., Naotsuka, M., Sato, K., Abe, S., Ohashi, K., Mizuno, K.
  • Organizer: 第34回日本 分子生物学会
  • Place of Presentation: 横浜
• [Presentation] Identification of Rho-GEFs involved in breast cancercell migration (2011)
  • Author(s): Hiatari, R., Tsuji, T., Hayashi, A., Ohashi, K., Mizuno, K.
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: 横浜
• [Presentation] Identification and functional roles of Rho-GEFs that are involved in cell migration (2011)
  • Author(s): Hayashi, A., Tsuji, T., Hiatari, R., Ohashi, K., Mizuno, K.
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] Phosphorylation and activation of LIMK1 by CaMKIIbeta in BDNF-induced dendritogenesis (2011)
  • Author(s): Ohashi, K., Saito, A., Kondo, H., Miyajima, K., Akatsuka, J., Kiuchi, T., Mizuno, K.
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] Activation of LIMK1 by CaMKIIb is required for BDNF-induced dendritogenesis in rat cortical neurons (2011)
  • Author(s): 大橋一正 、斎藤聡彦、宮島健、赤塚淳一、 木内泰、水野健作
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 札幌
• [Presentation] Identification ofRho-GEFs that are involved in mechanotransduction of vascular endothelial cells (2011)
  • Author(s): Ohashi, K., Abiko, H., Tsuji, T., Naotsuka, M., Hiatari, R., Sakamoto, N., Sato, M., Mizuno, K.
  • Organizer: The 6th International Symposium on Biomechanics in Vascular Biology and Cardiovascular Disease
  • Place of Presentation: Rotterdam, The Netherlands
• [Presentation] Regulation of Furry localization to spindle microtubules (2010)
  • Author(s): 池田真教, 他
  • Organizer: 第33回日本分子生物学会年会第83回日本生化学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] LIMK1 is required for BDNF-induced dendritogenesis through the PLCγ-CaMKII β signaling pathway (2010)
  • Author(s): 斉藤聡彦, 他
  • Organizer: 第33回日本分子生物学会年会第83回日本生化学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] 細胞移動時の接着斑のターンオーバーにおけるSlingshotファミリーの機能解析 (2010)
  • Author(s): 高橋克宣, 他
  • Organizer: 第33回日本分子生物学会年会第83回日本生化学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] 細胞骨格再編成を介した器官形態の制御メカニズムの解析 (2010)
  • Author(s): 森田梨津子, 他
  • Organizer: 第33回日本分子生物学会年会第83回日本生化学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] メカノストレス応答に関わるRho-GEFの網羅的探索 (2010)
  • Author(s): 安彦日和, 他
  • Organizer: 日本分子生物学会第10回春季シンポジウム
  • Place of Presentation: 宮城県松島
  • Year and Date: 2010-06-07
• [Presentation] 細胞内アクチンモノマー濃度と刺激依存的なラメリポディア形成との強い相関関係 (2010)
  • Author(s): 永井友朗, 他
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: 大阪
  • Year and Date: 2010-05-20
• [Presentation] Identification of Rho-GEFs involved in mechnotranduction of vascular endothelial cell (2010)
  • Author(s): Abiko, H., Tsuji, T., Naotsuka, M., Hiatari, R., Sakamoto, N., Sato, M., Ohashi, K., Mizuno, K.
  • Organizer: 第33回日本分子生物学会年会第83回日本生化学会合同大会
  • Place of Presentation: 神戸
• [Presentation] メカノストレス応答に関わるRho-GEFの網羅的探索 (2010)
  • Author(s): 安彦日和、辻拓史、直塚萌、大橋一正、坂元尚哉、佐藤正明、水野健作
  • Organizer: 日本分子生物学会第10回春季シンポジウム
  • Place of Presentation: 松島
• [Presentation] BDNFによるラット皮質神経細胞の樹状突起形成におけるCaMキナーゼ依存的LIMキナーゼ活性化の役割 (2010)
  • Author(s): 大橋一正、宮島健、斎藤聡彦、赤塚淳一、水野健作
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: 大阪
• [Remarks]
  • URL: http://www.lifesci.tohoku.ac.jp/teacher/ts_oohashi/
• [Remarks]
  • URL: http://www.biology.tohoku.ac.jp/lab-www/mizuno_lab/
• [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/
• [Remarks]
  • URL: http://www.biology.tohoku.ac.jp/lab-www/mizuno_lab/
• [Remarks]
  • URL: http://www.biology.tohoku.ac.jp/lab-www/mizuno_lab/