Abstract
In the social amoeba Dictyostelium discoideum, travelling waves of extracellular cyclic adenosine monophosphate (cAMP) self-organize in cell populations and direct aggregation of individual cells to form multicellular fruiting bodies. In contrast to the large body of studies that addressed how movement of cells is determined by spatial and temporal cues encoded in the dynamic cAMP gradients, how cell mechanics affect the formation of a self-generated chemoattractant field has received less attention. Here, we show, by live cell imaging analysis, that the periodicity of the synchronized cAMP waves increases in cells treated with the actin inhibitor latrunculin. Detail analysis of the extracellular cAMP-induced transients of cytosolic cAMP (cAMP relay response) in well-isolated cells demonstrated that their amplitude and duration were markedly reduced in latrunculin-treated cells. Similarly, in cells strongly adhered to a poly-l-lysine-coated surface, the response was suppressed, and the periodicity of the population-level oscillations was markedly lengthened. Our results suggest that cortical F-actin is dispensable for the basic low amplitude relay response but essential for its full amplification and that this enhanced response is necessary to establish high-frequency signalling centres. The observed F-actin dependence may prevent aggregation centres from establishing in microenvironments that are incompatible with cell migration.
Highlights
Cell movement and migration are often directed by self-generated diffusive extracellular signals; cells move according to the spatio-temporal profiles of molecules that are produced by themselves
The present results suggest that F-actin plays a critical role in the amplification of extracellular cyclic adenosine monophosphate (cAMP) and to initiate the population-level oscillations
The occurrence of the collective bursts of cAMP synthesis/secretion is determined by the accumulation ofnanomolar extracellular cAMP [18]
Summary
Cell movement and migration are often directed by self-generated diffusive extracellular signals; cells move according to the spatio-temporal profiles of molecules that are produced by themselves. Self-generated subcellular gradient of autocrine EGF signals stimulate motility and polarization [2]. Directionality of cell movement depends on mechanical parameters, such as surface rigidity and topography, confinement and adhesion [4]. F-actin formation in Dictyostelium is known to align along the nanoscale ridges on the surface substrate and induces biased directional movement [5]. Direction of fibroblast cell migration [6] as well as efficiency of neutrophil and macrophage migration depends on substrate stiffness [7,8]. How mechanical parameters influence synthesis and formation of a self-generated chemoattractant field has so far received little attention
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