Directional persistence of cell migration coincides with stability of asymmetric intracellular signaling.
Directional persistence of cell migration coincides with stability of asymmetric intracellular signaling.
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DOI：
10.1016/j.bpj.2009.09.051
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发表时间：
2010-01
影响因子：
3.4
通讯作者：
Michael Weiger;Shoeb Ahmed;Erik S. Welf;J. Haugh
中科院分区：
文献类型：
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作者：
Michael Weiger;Shoeb Ahmed;Erik S. Welf;J. Haugh
长期以来，人们已经认识到，细胞迁移的时空动力学是在细胞内信号传导途径的控制下，细胞内信号传导途径由粘附受体和其他细胞外信号转导物介导。此外，有充分的证据表明，细胞迁移的各个方面是随机的：否则它怎么可能在比典型的信号转导过程长得多的时间尺度上表现出方向性持久性，并被方向的突然变化所打断？然而，信号传导过程影响这些行为的机制仍不清楚。我们已经开发了相关的平行活细胞显微镜测量细胞迁移动力学的细胞内信号转导过程，管理他们的分析方法。在随机迁移的成纤维细胞中磷酸肌醇3激酶信号传导的分析中，我们观察到强烈信号传导的热点与局部细胞突起相一致，并且与细胞迁移持久性相对应的特征寿命相一致。我们进一步表明，遥远的热点是动态和随机耦合。这些结果表明，细胞迁移方向的变化是由相对快速的细胞内信号传导过程的脆弱平衡决定的。
It has long been appreciated that spatiotemporal dynamics of cell migration are under the control of intracellular signaling pathways, which are mediated by adhesion receptors and other transducers of extracellular cues. Further, there is ample evidence that aspects of cell migration are stochastic: how else could it exhibit directional persistence over timescales much longer than typical signal transduction processes, punctuated by abrupt changes in direction? Yet the mechanisms by which signaling processes affect those behaviors remain unclear. We have developed analytical methods for relating parallel live-cell microscopy measurements of cell migration dynamics to the intracellular signaling processes that govern them. In this analysis of phosphoinositide 3-kinase signaling in randomly migrating fibroblasts, we observe that hot spots of intense signaling coincide with localized cell protrusion and endure with characteristic lifetimes that correspond to those of cell migration persistence. We further show that distant hot spots are dynamically and stochastically coupled. These results are indicative of a mechanism by which changes in a cell's direction of migration are determined by a fragile balance of relatively rapid intracellular signaling processes.