Abstract
Cell migration is driven by the establishment of disparity between the cortical properties of the softer front and the more rigid rear allowing front extension and actomyosin-based rear contraction. However, how the cortical actin meshwork in the rear is generated remains elusive. Here we identify the mDia1-like formin A (ForA) from Dictyostelium discoideum that generates a subset of filaments as the basis of a resilient cortical actin sheath in the rear. Mechanical resistance of this actin compartment is accomplished by actin crosslinkers and IQGAP-related proteins, and is mandatory to withstand the increased contractile forces in response to mechanical stress by impeding unproductive blebbing in the rear, allowing efficient cell migration in two-dimensional-confined environments. Consistently, ForA supresses the formation of lateral protrusions, rapidly relocalizes to new prospective ends in repolarizing cells and is required for cortical integrity. Finally, we show that ForA utilizes the phosphoinositide gradients in polarized cells for subcellular targeting.
Highlights
Cell migration is driven by the establishment of disparity between the cortical properties of the softer front and the more rigid rear allowing front extension and actomyosin-based rear contraction
Since the hydrostatic pressure-driven blebs are a hallmark of migrating Dictyostelium cells in confined environments[6], and the loss of myosin II is detrimental for cell migration[24], we hypothesized specific actin assembly factors to exist in the rear that contribute to actomyosin-driven contractility
As the Arp2/3 complex is predominantly localized in the cell front, we systematically screened for the localization of as yet uncharacterized Dictyostelium formins by expression of green fluorescent protein (GFP) fusion proteins
Summary
Cell migration is driven by the establishment of disparity between the cortical properties of the softer front and the more rigid rear allowing front extension and actomyosin-based rear contraction. As utilized by immune cells or Dictyostelium amoebae, is instead characterized by rounder shape, weaker adhesion, absence of stress fibres and formation of actin-rich pseudopods or hydrostatic pressure-driven blebs in their fronts and myosin-II-driven contractility in the rears[5,6]. These distinct motility modes are extremes of a broad spectrum characterized by smooth transitions. Arp2/3 complex perturbation potentiated the effect of mDia[1] depletion, suggesting that mDia[1] and Arp2/3 play different roles in cortex function
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