Spatiotemporal dynamics of RhoA activity in migrating cells
Spatiotemporal dynamics of RhoA activity in migrating cells
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DOI：
10.1038/nature04665
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发表时间：
2006-04-20
期刊：
影响因子：
64.8
通讯作者：
Hahn, KM
中科院分区：
文献类型：
--
作者：
Pertz, O;Hodgson, L;Hahn, KM
Rho家族GTPases调节控制细胞迁移的肌动蛋白和粘附动力学。目前的模型假设Rac促进细胞膜前缘的突出，而RhoA调节细胞体的收缩性（1,2）。然而，有证据表明RhoA也调节膜突出（3,4）。在这里，我们使用一种荧光生物传感器，基于一种新颖的设计，保留可逆的膜相互作用，来可视化RhoA活性在细胞迁移过程中的时空动态。在随机迁移的细胞中，RhoA活性直接集中在突起边缘的锐带中。偶见于缩尾处，在细胞体处较低。RhoA活性也与外周褶边和胞泡相关，但与血小板衍生生长因子（PDGF）诱导的背侧褶边无关。与随机迁移的细胞相比，PDGF诱导的膜突起具有较低的RhoA活性，这可能是因为PDGF强烈激活Rac，而Rac先前已被证明可以拮抗RhoA活性（5,6）。因此，我们的数据表明，不同的细胞外信号在膜突出过程中诱导不同的RhoA信号传导模式。
Rho family GTPases regulate the actin and adhesion dynamics that control cell migration. Current models postulate that Rac promotes membrane protrusion at the leading edge and that RhoA regulates contractility in the cell body(1,2). However, there is evidence that RhoA also regulates membrane protrusion(3,4). Here we use a fluorescent biosensor, based on a novel design preserving reversible membrane interactions, to visualize the spatiotemporal dynamics of RhoA activity during cell migration. In randomly migrating cells, RhoA activity is concentrated in a sharp band directly at the edge of protrusions. It is observed sporadically in retracting tails, and is low in the cell body. RhoA activity is also associated with peripheral ruffles and pinocytic vesicles, but not with dorsal ruffles induced by platelet-derived growth factor (PDGF). In contrast to randomly migrating cells, PDGF-induced membrane protrusions have low RhoA activity, potentially because PDGF strongly activates Rac, which has previously been shown to antagonize RhoA activity(5,6). Our data therefore show that different extracellular cues induce distinct patterns of RhoA signalling during membrane protrusion.