Tensin 2 modulates cell contractility in 3D collagen gels through the RhoGAP DLC1 |
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Authors: | Katherine Clark Jonathan D Howe Christine E Pullar J Angelo Green Vira V Artym Kenneth M Yamada David R Critchley |
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Institution: | 1. Department of Biochemistry, University of Leicester, Leicester LE1 9HN, UK;2. Department of Cell Physiology and Pharmacology, University of Leicester, Leicester LE1 9HN, UK;3. Laboratory of Cell and Developmental Biology, NIDCR, NIH, Bethesda, Maryland 20892;4. Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical School, Washington, District of Columbia 20057 |
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Abstract: | Cytoskeletal proteins of the tensin family couple integrins to the actin cytoskeleton. They are found in both focal adhesions and the fibrillar adhesions formed between cells and the fibronectin matrix. There are four tensin genes which encode three large (~200 kDa) tensin isoforms (tensin 1, 2, 3) and one short isoform (cten). However, the subcellular localization and function of the individual isoforms is poorly understood. Using human foreskin fibroblasts (HFFs), and imaging on both fixed and live cells, we show that GFP‐tensin 2 is enriched in dynamic focal adhesions at the leading edge of the cell, whereas GFP‐tensin 3 translocates rearward, and is enriched in fibrillar adhesions. To investigate the possible role of tensins in cell‐matrix remodeling, we used siRNAs to knockdown each tensin isoform. We discovered that tensin 2 knockdown significantly reduced the ability of HFFs to contract 3D collagen gels, whilst no effect on fibronectin fibrillogenesis was observed. This inhibition of collagen gel contraction was associated with a substantial reduction in Rho activity, and it was reversed by depletion of DLC1, a RhoGAP that binds to tensin in focal adhesions. These findings suggest that focal adhesion‐localized tensin 2 negatively regulates DLC1 to permit Rho‐mediated actomyosin contraction and remodeling of collagen fibers. J. Cell. Biochem. 109: 808–817, 2010. © 2010 Wiley‐Liss, Inc. |
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Keywords: | tensin fibronectin matrix assembly fibrillar adhesion collagen contraction DLC1 RhoGAP |
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