Abstract
ABSTRACTMotile cells manifest increased migration speed and directionality in gradients of stimuli, including chemoattractants, electrical potential and substratum stiffness. Here, we demonstrate that Dictyostelium cells move directionally in response to an electric field (EF) with specific acceleration/deceleration kinetics of directionality and migration speed. Detailed analyses of the migration kinetics suggest that migration speed and directionality are separately regulated by Gβ and RasG, respectively, in EF-directed cell migration. Cells lacking Gβ, which is essential for all chemotactic responses in Dictyostelium, showed EF-directed cell migration with the same increase in directionality in an EF as wild-type cells. However, these cells failed to show induction of the migration speed upon EF stimulation as much as wild-type cells. Loss of RasG, a key regulator of chemoattractant-directed cell migration, resulted in almost complete loss of directionality, but similar acceleration/deceleration kinetics of migration speed as wild-type cells. These results indicate that Gβ and RasG are required for the induction of migration speed and directionality, respectively, in response to an EF, suggesting separation of migration speed and directionality even with intact feedback loops between mechanical and signaling networks.
Highlights
Directional cell migration is a highly coordinated process of motility, directional sensing and polarity
Large-scale screening for electrotaxis phenotypes Previously, we developed a high-throughput screening technique and performed large-scale screening to find mutants with electrotaxis phenotypes from a collection of 365 D. discoideum strains with morphological defects (Gao et al, 2015)
The 2-D analysis of the phenotypes of the collection of mutants demonstrates that the defects in the control of directionality are not necessarily linked with those of migration speed, suggesting the possibility that directionality and migration speed of cells might be separately regulated in directed cell migration in an electric field (EF)
Summary
Directional cell migration is a highly coordinated process of motility (migration speed), directional sensing and polarity. Motility refers to the ability of cells to move around randomly by extending pseudopods. When exposed to external cues, cells determine the direction of movement by sensing the spatial and temporal information of the external signals, referred to as directional sensing, and persistently move toward the direction of the gradient with forming a. Directional sensing and polarity establishment are mediated by a system that detects temporal and spatial stimuli and biases motility toward a certain direction (Artemenko et al, 2014; Shi et al, 2013). There have been numerous studies over the past several decades that investigated these processes and several signaling molecules involved in the directional cell migration have been characterized. The interrelationships, the coordinate regulation and the underlying molecular mechanisms of these sophisticated processes remain largely unknown
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