Tensin 2 modulates cell contractility in 3D collagen gels through the RhoGAP DLC1.
Tensin 2 modulates cell contractility in 3D collagen gels through the RhoGAP DLC1.
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DOI：
10.1002/jcb.22460
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发表时间：
2010-03-01
影响因子：
4
通讯作者：
Critchley, David R.
中科院分区：
文献类型：
--
作者：
Clark, Katherine;Howe, Jonathan D.;Pullar, Christine E.;Green, J. Angelo;Artym, Vira V.;Yamada, Kenneth M.;Critchley, David R.
张力蛋白家族的细胞骨架蛋白将整合素与肌动蛋白细胞骨架偶联。它们存在于细胞与纤连蛋白基质之间形成的粘着斑和纤维状粘连中。有四种张力蛋白基因，编码三种大 (~200 kDa) 张力蛋白亚型（张力蛋白 1、2、3）和一种短亚型 (cten)。然而，人们对各个亚型的亚细胞定位和功能知之甚少。使用人包皮成纤维细胞 (HFF)，并对固定细胞和活细胞进行成像，我们发现 GFP-张力蛋白 2 在细胞前缘的动态粘着斑中富集，而 GFP-张力蛋白 3 向后移位，在纤维状粘连中富集。为了研究张力蛋白在细胞基质重塑中的可能作用，我们使用 siRNA 来敲除每种张力蛋白亚型。我们发现，张力蛋白 2 敲除显着降低了 HFF 收缩 3D 胶原凝胶的能力，而没有观察到对纤连蛋白纤维形成的影响。这种对胶原蛋白凝胶收缩的抑制与 Rho 活性的大幅降低有关，并且可以通过 DLC1（一种与粘着斑中的张力蛋白结合的 RhoGAP）的消耗来逆转。这些发现表明，粘着斑局部张力蛋白 2 负向调节 DLC1，以允许 Rho 介导的肌动球蛋白收缩和胶原纤维重塑。
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.
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DLC-1和CTEN的SH2结构域的磷酸酪氨酸独立的相互作用调节局灶性粘附定位和DLC-1的生长抑制活性。
影响因子：
7.8
作者：
Liao, Yi-Chun;Si, Lizhen;White, Ralph W. DeVere;Lo, Su Hao
通讯作者：
Lo, Su Hao
DOI：
10.1083/jcb.125.5.1067
发表时间：
1994-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lo SH;Janmey PA;Hartwig JH;Chen LB
通讯作者：
Chen LB
影响因子：
4.8
作者：
Brancaccio, M;Guazzone, S;Silengo, L
通讯作者：
Silengo, L
影响因子：
3.7
作者：
Chan, Lo-Kong;Ko, Frankie Chi Fat;Yam, Judy Wai Ping
通讯作者：
Yam, Judy Wai Ping
影响因子：
21.3
作者：
Katz, Menachem;Amit, Ido;Yarden, Yosef
通讯作者：
Yarden, Yosef