Mechanisms of mechanical force-induced Rho family activation and actin cytoskeletal reorganization
Project/Area Number |
24370051
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Functional biochemistry
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Research Institution | Tohoku University |
Principal Investigator |
MIZUNO Kensaku 東北大学, 生命科学研究科, 教授 (70128396)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
|
Keywords | 細胞・組織 / 細胞骨格 / Rho / メカニカルストレス / アクチン / 細胞極性 / メカノセンサー |
Outline of Final Research Achievements |
Rho family GTPases are crucial for mechanical force-induced actin cytoskeletal reorganization; however, the mechanism underlying force-induced activation of Rho family GTPases is unknown. A screen of short-hairpin RNAs targeting 63 Rho-guanine nucleotide exchange factors (Rho-GEFs) revealed that at least 11 Rho-GEFs are involved in cyclic-stretch-induced reorientation of vascular endothelial cells. Among 11 Rho-GEFs, Solo is involved in cell-cell-adhesion- and cadherin-mediated mechanical force-induced RhoA activation and reorientation of endothelial cells. We also identified at least 5 Rho-GEFs that are involved in extracellular matrix (ECM) stiffness-induced transformation of MCF-10A human breast epithelial cells cultured in 3D ECM conditions. Among them, Farp1 binds to integrins and plays a critical role in cell adhesion, proliferation, and morphogenesis.
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Report
(4 results)
Research Products
(36 results)
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[Journal Article] beta-arrestin-dependent regulation of the cofilin pathway is required for the scavenging activity of the atypical chemokine receptor D6.2013
Author(s)
Borroni, E. M., Cancellieri, C., Vacchini, A., Benureau, Y., Lagane, B., Bachelerie, F., Arenzana-Seisdedos, F., Mizuno, K., Mantovani, A., Bonecchi, R., and Locati, M.
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Journal Title
Sci. Signal.
Volume: (in press)(掲載確定)
Related Report
Peer Reviewed
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[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.
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Journal Title
Genes Cells
Volume: (in press)
Issue: 7
Pages: 533-543
DOI
Related Report
Peer Reviewed
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[Journal Article] Coactosin accelerates cell dynamism by promoting actin polymerization.2013
Author(s)
Hou, X., Katahira, T., Ohashi, K., Mizuno, K., Sugiyama, S, and Nakamura, H.
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Journal Title
Dev. Biol.
Volume: (in press)(掲載確定)
Related Report
Peer Reviewed
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[Journal Article] Novel PKCa-mediated phosphorylation site(s) on cofilin and their potential role in terminating histamine release.2012
Author(s)
Sakuma, M., Shirai, Y., Yoshino, K., Kuramasu, M., Nakamura, T., Yanagita, T., Mizuno. K.. Hide, I., Nakata, Y., and Saito, N.
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Journal Title
Mol. Biol. Cell
Volume: 23
Issue: 18
Pages: 3707-3721
DOI
Related Report
Peer Reviewed
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