Abstract
The extracellular matrix (ECM) is a major regulator of cell behavior. Recent studies have indicated the importance of the physical properties of the ECM, including its stiffness, for cell migration and differentiation. Using actomyosin-generated forces, cells pull the ECM and sense stiffness via cell-ECM adhesion structures called focal adhesions (FAs). Vinculin, an actin-binding FA protein, has emerged as a major player in FA-mediated mechanotransduction. Although vinculin is important for sensing ECM stiffness, the role of vinculin binding to actin in the ECM stiffness-mediated regulation of vinculin behavior remains unknown. Here, we show that an actin binding-deficient mutation disrupts the ECM stiffness-dependent regulation of CSB (cytoskeleton stabilization buffer) resistance and the stable localization of vinculin. These results suggest that the vinculin-actin interaction participates in FA-mediated mechanotransduction.
MeSH terms
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Actin Cytoskeleton / metabolism*
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Animals
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Cells, Cultured
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Extracellular Matrix / metabolism
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Focal Adhesions
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Mice
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Protein Binding
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Subcellular Fractions / metabolism
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Vinculin / genetics
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Vinculin / metabolism*
Grants and funding
This work was supported in part by The Naito Foundation(NK), a Grant-in-Aid for Scientific Research (B) (JSPS KAKENHI Grant Number 24380185)(NK), a Grant-in-aid for Exploratory Research (JSPS KAKENHI Grant Number 26660291, 16K15090)(NK) from The Japan Society for the Promotion of Science (
https://www.jsps.go.jp/english/index.html), Grants-in-Aid for Scientific Research (S) (25221203)(KU) and a Grant-in-Aid for Scientific Research on Innovative Areas (MEXT KAKENHI Grant Number 26112707)(NK) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (
http://www.mext.go.jp/en/), and the Advanced Research and Development Programs for Medical Innovation (NK) from Japan Agency for Medical Research and development (
http://www.amed.go.jp/en/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.