Wnt-3a-dependent cell motility involves RhoA activation and is specifically regulated by dishevelled-2
Wnt-3a-dependent cell motility involves RhoA activation and is specifically regulated by dishevelled-2
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DOI：
10.1074/jbc.m406391200
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发表时间：
2005-01-07
影响因子：
4.8
通讯作者：
Rubin, JS
中科院分区：
文献类型：
--
作者：
Endo, Y;Wolf, V;Rubin, JS
wnt刺激细胞迁移，尽管这一作用的机制尚不完全清楚。为了研究介导wnt依赖性细胞运动的途径，我们用wnt -3a条件培养基处理中国仓鼠卵巢细胞，并监测细胞形状和运动的变化。Wnt-3a诱导细胞扩散、突起结构形成、应力纤维重组和迁移。尽管Wnt-3a稳定了β -catenin，但β -catenin/canonical通路的两种抑制剂Dickkopf-1和显性阴性T细胞因子构建体并没有降低运动能力。小GTPase RhoA也被Wnt-3a激活。与β -连环蛋白信号传导相反，Rho激酶的抑制部分阻断了运动。由于disheveled （Dvl）蛋白是典型和非典型Wnt信号的效应物，我们使用免疫荧光分析和小干扰RNA技术来评估Dvl在细胞运动中的作用。特异性敲低Dvl-2表达可显著降低wnt -3a依赖性细胞形状和运动的变化，表明该Dvl亚型在介导中国仓鼠卵巢细胞wnt -3a依赖性运动中起主导作用。
Wnts stimulate cell migration, although the mechanisms responsible for this effect are not fully understood. To investigate the pathways that mediate Wnt-dependent cell motility, we treated Chinese hamster ovary cells with Wnt-3a-conditioned medium and monitored changes in cell shape and movement. Wnt-3a induced cell spreading, formation of protrusive structures, reorganization of stress fibers and migration. Although Wnt-3a stabilized beta-catenin, two inhibitors of the beta-catenin/canonical pathway, Dickkopf-1 and a dominant-negative T cell factor construct, did not reduce motility. The small GTPase RhoA also was activated by Wnt-3a. In contrast to beta-catenin signaling, inhibition of Rho kinase partially blocked motility. Because Dishevelled (Dvl) proteins are effectors of both canonical and noncanonical Wnt signaling, we used immunofluorescent analysis and small interference RNA technology to evaluate the role of Dvl in cell motility. Specific knock-down of Dvl-2 expression markedly reduced Wnt-3a-dependent changes in cell shape and movement, suggesting that this Dvl isoform had a predominant role in mediating Wnt-3a-dependent motility in Chinese hamster ovary cells.