1. Altering the threshold of an excitable signal transduction network changes cell migratory modes
- Author
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Takanari Inoue, Huaqing Cai, Peter N. Devreotes, Sayak Bhattacharya, Yuchuan Miao, Marc Edwards, and Pablo A. Iglesias
- Subjects
0301 basic medicine ,Phosphatidylinositol 4,5-Diphosphate ,Cell type ,Time Factors ,Cell ,Green Fluorescent Proteins ,Biosensing Techniques ,Time-Lapse Imaging ,Article ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,medicine ,Cyclic AMP ,Computer Simulation ,Dictyostelium ,Computational analysis ,Cell Shape ,Cytoskeleton ,biology ,Effector ,Chemistry ,Cell Membrane ,Cell Biology ,biology.organism_classification ,Control cell ,Signal transduction network ,Actins ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Signal transduction ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
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. more...
- Published
- 2017