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Miao, Yuchuan, Bhattacharya, Sayak, Edwards, Marc, Cai, Huaqing, Inoue, Takanari, Iglesias, PA Pablo A, Devreotes, PN Peter N, (2017) ' Altering the threshold of an excitable signal transduction network changes cell migratory modes. ' Nat. Cell Biol. 19 329-340

 

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.
Status:	ppublish	Type:	Journal article	Source:	PUBMED	PubMed ID:	28346441

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	Genes addressed in this paper
	amiB	gpgA	piaA	pikI	pkbA	pkgB	rasC	rasG
Topics in this paper
Genetic Interactions					X	X	X	X
Mutants/Phenotypes	X	X	X	X	X	X	X	X
Chemotaxis/Motility	X	X	X	X	X	X	X	X
Signal Transduction	X	X	X	X	X	X	X	X