Miao Yuchuan, Bhattacharya Sayak, Edwards Marc, Cai Huaqing, Inoue Takanari, Iglesias Pablo A, Devreotes Peter N
Department of Biological Chemistry, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Department of Electrical and Computer Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Nat Cell Biol. 2017 Apr;19(4):329-340. doi: 10.1038/ncb3495. Epub 2017 Mar 27.
The diverse migratory modes displayed by different cell types are generally believed to be idiosyncratic. Here we show that the migratory behaviour of Dictyostelium was switched from amoeboid to keratocyte-like and oscillatory modes by synthetically decreasing phosphatidylinositol-4,5-bisphosphate levels or increasing Ras/Rap-related activities. The perturbations at these key nodes of an excitable signal transduction network initiated a causal chain of events: the threshold for network activation was lowered, the speed and range of propagating waves of signal transduction activity increased, actin-driven cellular protrusions expanded and, consequently, the cell migratory mode transitions ensued. Conversely, innately keratocyte-like and oscillatory cells were promptly converted to amoeboid by inhibition of Ras effectors with restoration of directed migration. We use computational analysis to explain how thresholds control cell migration and discuss the architecture of the signal transduction network that gives rise to excitability.
不同细胞类型所表现出的多样迁移模式通常被认为是特异的。在此我们表明，通过合成降低磷脂酰肌醇 - 4,5 - 二磷酸水平或增加Ras/Rap相关活性，盘基网柄菌的迁移行为从阿米巴样模式转变为角质细胞样和振荡模式。在这个可兴奋信号转导网络的这些关键节点处的扰动引发了一系列因果事件：网络激活的阈值降低，信号转导活动传播波的速度和范围增加，肌动蛋白驱动的细胞突起扩展，因此细胞迁移模式随之转变。相反，通过抑制Ras效应器并恢复定向迁移，天生的角质细胞样和振荡细胞迅速转变为阿米巴样。我们使用计算分析来解释阈值如何控制细胞迁移，并讨论产生兴奋性的信号转导网络的结构。
