ZRP-1 controls Rho GTPase-mediated actin reorganization by localizing at cell-matrix and cell-cell adhesions
ZRP-1 controls Rho GTPase-mediated actin reorganization by localizing at cell-matrix and cell-cell adhesions
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DOI：
10.1242/jcs.03477
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发表时间：
2007-08-15
影响因子：
4
通讯作者：
Yamamoto, Tadashi
中科院分区：
文献类型：
--
作者：
Bai, Chen-Yu;Ohsugi, Miho;Yamamoto, Tadashi
粘着斑蛋白ZRP-1/TRIP 6参与肌动蛋白重组和细胞运动。然而，ZRP-1的作用仍然不清楚，因为以前报道的数据经常相互矛盾。在本研究中，我们研究了ZRP-1在HeLa细胞中的作用。ZRP-1定位于HeLa细胞中的细胞-细胞接触位点以及细胞-基质接触位点。RNA干扰介导的ZRP-1从HeLa细胞的耗竭表明，ZRP-1是必不可少的，不仅为应力纤维的形成和组装的成熟粘着斑，而且为肌动蛋白重组在细胞-细胞接触点和正确的细胞-细胞粘附，因此，集体细胞迁移。由ZRP-1缺失引起的局灶性粘连和应力纤维的损伤与FAK的酪氨酸磷酸化减少有关。然而，局灶性粘连的成熟不能通过表达活性FAK来恢复。有趣的是，ZRP-1耗竭细胞中的应力纤维通过RhoA的外源性表达得到改善。我们还发现，在ZRP-1缺失的细胞中，总Rac 1活性升高，导致肌动蛋白聚合和动态膜突起的异常爆发。综上所述，我们得出结论，ZRP-1通过定位于细胞-基质和细胞-细胞接触位点，在细胞-基质/细胞-细胞接触信号与Rho GTP酶介导的肌动蛋白重塑的偶联中起着至关重要的作用。
Focal adhesion protein ZRP-1/TRIP6 has been implicated in actin reorganization and cell motility. The role of ZRP-1, however, remained obscure because previously reported data are often conflicting one another. In the present study, we examined roles of ZRP-1 in HeLa cells. ZRP-1 is localized to the cell-cell contact sites as well as to cell-matrix contact sites in HeLa cells. RNA-interference-mediated depletion of ZRP-1 from HeLa cells revealed that ZRP-1 is essential not only for the formation of stress fibers and assembly of mature focal adhesions, but also for the actin reorganization at cell-cell contact sites and for correct cell-cell adhesion and, thus, for collective cell migration. Impairment of focal adhesions and stress fibers caused by ZRP-1 depletion has been associated with reduced tyrosine phosphorylation of FAK. However, maturation of focal adhesions could not be recovered by expression of active FAK. Interestingly, stress fibers in ZRP-1-depleted cells were ameliorated by exogenous expression of RhoA. We also found that total Rac1 activity is elevated in ZRP-1-depleted cells, resulting in abnormal burst of actin polymerization and dynamic membrane protrusions. Taken together, we conclude that that ZRP-1 plays a crucial role in coupling the cell-matrix/cell-cell-contact signals with Rho GTPase-mediated actin remodeling by localizing at cell-matrix and cell-cell contact sites.