Activator-inhibitor coupling between Rho signalling and actin assembly makes the cell cortex an excitable medium

Cytokinesis is a process that divides the cytoplasm of a cell into two daughter cells. It relies on localized actomyosin contractility driven by Rho GTPase activity. While Rho's role in actin assembly is established, how this activity is spatially and temporally controlled remains unclear. Prior research has shown that Rho activation is necessary for actin polymerization, but the mechanisms regulating Rho's spatial distribution are less understood. An open question is how the cortex becomes selectively responsive to signals during specific cell cycle phases. This gap motivated investigations into the dynamics of Rho and actin interactions. No prior work had resolved the relationship between Rho activity and F-actin's potential inhibitory role. Understanding this could clarify how cytokinesis is regulated. The cell cycle phase following anaphase is critical for cortical responsiveness. This study addresses the mechanisms underlying Rho's dynamic behavior.

The aim of the study was to investigate how Rho signaling and actin assembly interact to regulate cytokinesis. The researchers focused on the equatorial cortex of oocytes and embryonic cells in frogs and echinoderms. They sought to determine if Rho activity is patterned during anaphase and how this activity is modulated. The study aimed to clarify the role of cyclin-dependent kinase 1 (Cdk1) in wave propagation. The researchers also wanted to identify the role of Ect2, a Rho GEF, in Rho activation. They hypothesized that F-actin might not only be a product of Rho activity but also a regulator of it. The study aimed to test if the cortex behaves as an excitable medium. Understanding this could explain the spatial and temporal control of cytokinesis.

The researchers used a combination of experimental and computational approaches. They examined Rho activity and F-actin dynamics in oocytes and embryonic cells of frogs and echinoderms. Fluorescent labeling was used to visualize Rho activity and actin polymerization. Time-lapse imaging captured cortical waves following anaphase onset. The study included pharmacological inhibition of Cdk1 to assess its role in wave propagation. Ect2 was manipulated to determine its necessity in Rho activation. Mathematical modeling was employed to simulate the reaction-diffusion system. The model incorporated Rho as an activator and F-actin as an inhibitor. Experimental data were compared with model predictions to validate the excitable dynamics hypothesis.

The study found that Rho activity and F-actin polymerization form waves shortly after anaphase onset. These waves are modulated by Cdk1 activity, which influences their propagation. Ect2 is essential for Rho activation, as its inhibition disrupted wave formation. Surprisingly, F-actin was found to inactivate Rho after initial activation. This suggests a feedback loop where Rho promotes actin assembly, and actin inhibits Rho. The waves were modeled as excitable dynamics in a reaction-diffusion system. The model predicted that Rho acts as an activator while F-actin functions as an inhibitor. This excitable behavior explains the spatial and temporal regulation of cytokinesis. The findings suggest that the cortex behaves as an excitable medium during anaphase.

The authors propose that the excitable dynamics of Rho and F-actin explain the spatial and temporal regulation of cytokinesis. The study shows that Rho activity is patterned in waves that are modulated by Cdk1 and require Ect2. The feedback loop between Rho and F-actin suggests a self-regulating mechanism. The excitable behavior of the cortex may explain its responsiveness to spindle signals. The findings support the idea that the cortex is an excitable medium during anaphase. The study provides a computational model that aligns with experimental results. The model incorporates Rho as an activator and F-actin as an inhibitor. The authors suggest that this excitable system underlies fundamental features of cytokinesis.