Cortical excitability and cell division

Abstract

As the interface between the cell and its environment, the cell cortex must be able to respond to a variety of external stimuli. This is made possible in part by cortical excitability, a behavior driven by coupled positive and negative feedback loops that generate propagating waves of actin assembly in the cell cortex. Cortical excitability is best known for promoting cell protrusion and allowing the interpretation of and response to chemoattractant gradients in migrating cells. It has recently become apparent, however, that cortical excitability is involved in the response of the cortex to internal signals from the cell-cycle regulatory machinery and the spindle during cell division. Two overlapping functions have been ascribed to cortical excitability in cell division: control of cell division plane placement, and amplification of the activity of the small GTPase Rho at the equatorial cortex during cytokinesis. Here, we propose that cortical excitability explains several important yet poorly understood features of signaling during cell division. We also consider the potential advantages that arise from the use of cortical excitability as a signaling mechanism to regulate cortical dynamics in cell division.

Rho and F-actin self-organize within an artificial cell cortex

“…Additionally, imaging a two-dimensional cortex is more straightforward than imaging a three-dimensional cell, where the cortex changes shape to accommodate cell movement and cytokinesis. [7][8][9][10] This system, however, is not well suited for studies investigating feedback between membrane topologies and cortical waves, as has been characterized in mast cells. 20,21 The reconstituted cortical Rho waves and oscillations shown here exhibit many properties that are similar to cortical waves described in developing embryos; 7,9 however, there are also clear differences.…”

“…[7][8][9][10] This system, however, is not well suited for studies investigating feedback between membrane topologies and cortical waves, as has been characterized in mast cells. 20,21 The reconstituted cortical Rho waves and oscillations shown here exhibit many properties that are similar to cortical waves described in developing embryos; 7,9 however, there are also clear differences. The excitable, traveling active Rho and F-actin waves identified here do not form a periodic pattern, which our data suggest may be due to changes in SLB fluidity after extract addition.…”

“…Alternatively, accumulation of bundled F-actin may not provide the right balance of negative feedback to support Rho excitability without suppressing wave propagation. [7][8][9] Another difference is that reconstituted oscillatory dynamics do not show robust propagation in space. Close inspection of kymographs of oscillations (Figure 2B) suggests there may be shortlived local propagation that is not detectable by our analysis methods.…”

Cell cycle and developmental control of cortical excitability in Xenopus laevis

“…One such behavior is cortical excitability, loosely defined as the ability of the cell cortex to generate traveling waves of filamentous actin (F-actin) polymerization and F-actin regulator protein recruitment. Excitability and related dynamics, such as oscillations, are thought to result from intertwined positive and negative feedback loops, with the former driving the traveling wave front forward at a constant velocity and the latter following closely behind to extinguish the trailing edge of the wave (for review see Michaud et al ., 2021). While cortical waves of F-actin were first reported over twenty years ago (Vicker, 2000), improvements in imaging technology and molecular probes have led to a steady increase in the number of cell types reported to exhibit cortical excitability.…”

Enhanced chemotaxis through spatially-regulated absolute concentration robustness

“…The characteristics of the pseudopods for cells that are migrating randomly or following a chemoattractant gradient are quite similar [8], suggesting that there is a common mechanism regulating the formation of a pseudopod, and that chemoat-tractant receptor occupancy is used solely to spatially guide this process. During the past fifteen years, it has been increasingly clear that the appearance of these extensions in Dictyostelium cells is regulated by an excitable system [10, 11]. The movement of cells using an excitable system is not limited to these amoebae.…”