Analysis of molecular mechanim for sensing stiffness of extracellular matrix

• Project/Area Number: 24380185
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Applied molecular and cellular biology
• Research Institution: Kyoto University
• Principal Investigator: KIOKA Noriyuki 京都大学, (連合)農学研究科(研究院), 准教授 (90234179)
• Co-Investigator(Renkei-kenkyūsha): 原田 伊知郎 東京工業大学, 生命理工学研究科, 助教 (00361759) ; 木村 泰久 京都大学, 大学院農学研究科, 助教 (10415143)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2013: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2012: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: 細胞外マトリックス / コラーゲン / メカノバイオロジー / がん / 接着斑 / 細胞接着 / 生体分子 / シグナル伝達 / 細胞・組織 / 癌 / 細胞分化

Outline of Final Research Achievements

Recent evidences have shown that stiffness of extracellular matrix(ECM) plays a critical role in regulating cell behaviors. Our research has clarified that an interaction of a focal adhesion protein vinculin with another focal adhesion protein vinexin works as a sensor for ECM stiffness. In addition, we have also found that Dlg5, a vinexin-binding protein, regulates cell migration and invasion of prostate cancer cell line via Akt-Girdin pathway. These observations shed light on mechanisms for sensing ECM stiffness and directing cell behaviors.

Research Products

• [Journal Article] Loss of Dlg5 expression promotes the migration and invasion of prostate cancer cells via Girdin phosphorylation (2014)
  • Author(s): Tomiyama, L., Sezaki, T., Matsuo, M., Ueda, K. and Kioka, N.
  • Journal Title: Oncogene Volume: 33 Issue: 9 Pages: 1141-1149
  • DOI: 10.1038/onc.2014.31
  • Peer Reviewed
• [Journal Article] Interaction of the vinculin proline-rich linker region with vinexin α in sensing extracellular matrix stiffness (2014)
  • Author(s): Hiroshi Yamashita, Takafumi Ichikawa, Daisuke Matsuyama, Yasuhisa Kimura, Kazumitsu Ueda, Susan W. Craig, Ichiro Harada, and Noriyuki Kioka
  • Journal Title: Journal of Cell Science Volume: 127 Pages: 1875-86
  • DOI: 10.1242/jcs.133645
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Non-specific protein modifications by a phytochemical induce heat shock response for self-defense (2013)
  • Author(s): Kohta Ohnishi
  • Journal Title: PLoS One Volume: 8(3) Issue: 3 Pages: 1-15
  • DOI: 10.1371/journal.pone.0058641
  • Peer Reviewed / Open Access
• [Journal Article] Dlg5 interacts with the TGF-beta receptor and promotes its degradation (2013)
  • Author(s): Takuhito Sezaki, Lucia Tomiyama, Yasuhisa
  • Journal Title: FEBS Lett Volume: (in press) Issue: 11 Pages: 1624-1629
  • DOI: 10.1016/j.febslet.2013.04.015
  • Peer Reviewed
• [Journal Article] Vinexin-beta protects against cardiac hypertrophy by blocking the Akt-dependent signalling pathway (2013)
  • Author(s): Chen, K. Gao, L. Liu, Y. Zhang, Y. Jiang, D. S. Wei, X. Zhu, X. H. Zhang, R. Chen, Y. Yang, Q. Kioka. N. Zhang. X
  • Journal Title: Basic research in cardiology Volume: 108 Issue: 2 Pages: 338-338
  • DOI: 10.1007/s00395-013-0338-0
  • Peer Reviewed
• [Journal Article] Role of Dlg5/1p-dlg, a membrane-associated guanylate kinase family protein, in epithelial-mesenchymal transition in LLc-PK1 renal epithelial cells (2012)
  • Author(s): Takuhito Sezaki, Kohki Inada, Takayuki Sogabe, Kumiyo Kakuda, Lucia Tomiyama, Yohsuke Matsuno, Takafumi Ichikawa, Michinori Matsuo, Kazumitsu Ueda, Noriyuki Kioka
  • Journal Title: PLoS ONE Volume: 7 Issue: 4 Pages: e35519-e35519
  • DOI: 10.1371/journal.pone.0035519
  • Peer Reviewed
• [Journal Article] ATP hydrolysis-dependent conformational changes in the extracellular domain of ABCA1 are associated with apoA-I binding. (2012)
  • Author(s): Nagao, K., Takahashi, K., Azuma, Y., Takada, M., Kimura, Y., Matsuo, M., Kioka, N. and Ueda, K.
  • Journal Title: J Lipid Res Volume: 53 Issue: 1 Pages: 126-136
  • DOI: 10.1194/jlr.m019976
  • Peer Reviewed
• [Presentation] 接着斑タンパク質ビネキシンαの両親媒性へリックスはビンキュリンと相互作用する (2015)
  • Author(s): 日野直也、市川尚文、木村泰久、植田和光、木岡紀幸
  • Organizer: 日本農芸化学会2015年度大会
  • Place of Presentation: 岡山
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] 細胞外マトリクスの硬さ感知におけるビンキュリンのアクチン繊維結合能の重要性 (2015)
  • Author(s): 大町朋弘、市川尚文、木村泰久、植田和光、木岡紀幸
  • Organizer: 日本農芸化学会2015年度大会
  • Place of Presentation: 岡山
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] 細胞外基質の硬さを感知するメカノセンサー (2015)
  • Author(s): 木岡紀幸
  • Organizer: 日本農芸化学会2015年度大会
  • Place of Presentation: 岡山
  • Year and Date: 2015-03-26 – 2015-03-29
  • Invited
• [Presentation] Loss of Dlg5 expression promotes the migration and invasion of prostate cancer cells via Girdin phosphorylation (2014)
  • Author(s): Lucia Tomiyama, Takuhito Sezaki, Michinori Matsuo, Kazumitsu Ueda, and Noriyuki Kioka
  • Organizer: 2014 Annual Meeting of The American Society for Cell Biology
  • Place of Presentation: Philadelphia, Pennsylvania, USA
  • Year and Date: 2014-12-06 – 2014-12-10
• [Presentation] Comparison of the effect of the vinexin family proteins on vinculin-mediated mechanosensing (2014)
  • Author(s): Takafumi Ichikawa, Masahiro Kita, Takuhito Sezaki, Shian-Huey Chiang, Alan R. Saltiel, Yasuhisa Kimura, Kazumitsu Ueda, Noriyuki Kioka
  • Organizer: 2014 Annual Meeting of The American Society for Cell Biology
  • Place of Presentation: Philadelphia, Pennsylvania, USA
  • Year and Date: 2014-12-06 – 2014-12-10
• [Presentation] 軟骨細胞分化における接着斑タンパク質ビネキシンの役割 (2014)
  • Author(s): 椀谷友紀、木村泰久、植田和光、木岡紀幸
  • Organizer: 2014年度日本農芸化学会関西支部大会
  • Place of Presentation: 奈良
  • Year and Date: 2014-09-20
• [Presentation] Interaction of the vinculin proline-rich linker region with vinexin alpha in sensing extracellular matrix stiffness (2014)
  • Author(s): Takafumi Ichikawa, Hiroshi Yamashita, Daisuke Matsuyama, Yasuhisa Kimura, Kazumitsu Ueda, Susan W. Craig, Ichiro Harada, and Noriyuki Kioka
  • Organizer: International symposium on Mechanobiology
  • Place of Presentation: 岡山
  • Year and Date: 2014-05-20 – 2014-05-23
• [Presentation] 結合能と接着斑増強効果を指標としたビネキシンファミリー（Sorbs）タンパク質の機能の比較解析 (2014)
  • Author(s): 喜多真弘、市川尚文、瀬崎拓人、松尾道憲、植田和光、木岡紀幸
  • Organizer: 日本農芸化学会2014年度大会
  • Place of Presentation: 東京
• [Presentation] 細胞外マトリックスの硬さを感知するメカノセンサーとしての“接着斑” (2013)
  • Author(s): 木岡紀幸
  • Organizer: 理研シンポジウム「最先端光計測とライフサイエンスの近未来-バイオラマン2017-
  • Place of Presentation: 松山
  • Invited
• [Presentation] 細胞外マトリクスの硬さの感知におけるビンキュリン-ビネキシンα相互作用 (2013)
  • Author(s): 市川尚文, 山下寛, 木村泰久, 植田和光, 木岡紀幸
  • Organizer: 第480回農芸化学会関西支部講演会
  • Place of Presentation: 大阪
• [Presentation] Comparing the effect on focal adhesion among vinexin family (Sorbs) proteins (2013)
  • Author(s): Masahiro kita, Takafumi Ichikawa, Takuhito sezaki, Michinori Matsuo, Kazumitsu Ueda and Noriyuki Kioka
  • Organizer: 第６５回日本細胞生物学会大会
  • Place of Presentation: 愛知
• [Presentation] 接着斑タンパク質ビンキュリンは間葉系幹細胞のECMの硬さ依存的な脂肪細胞分化抑制に必要である (2013)
  • Author(s): 黒田美都、和田洋樹、植田和光、木岡紀幸
  • Organizer: 第36回日本分子生物学会
  • Place of Presentation: 神戸
• [Presentation] 細胞外マトリックスの堅さの感知におけるビンキュリン-ビネキシン相互作用 (2012)
  • Author(s): 木岡紀幸
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡(招待講演)
• [Remarks]
  • URL: http://www.biochemistry.kais.kyoto-u.ac.jp/
• [Remarks] 京都大学細胞生化学分野業績
  • URL: http://www.biochemistry.kais.kyoto-u.ac.jp/gyouseki/gyouseki.html