Contractile ring constriction and septation in fission yeast are integrated mutually stabilizing processes

Abstract

In common with other cellular machineries, the actomyosin contractile ring that divides cells during cytokinesis does not operate in isolation. Contractile rings in animal cells interact with contiguous actomyosin cortex, while ring constriction in many cell-walled organisms couples tightly to cell wall growth. In fission yeast, a septum grows in the wake of the constricting ring, ensuring cytokinesis leaves two daughter cells fully enclosed by cell wall. Here we mathematical modeled the integrated constriction-septation system in fission yeast, with a kinetic growth model evolving the 3D septum shape coupled to a molecularly explicit simulation of the contractile ring highly constrained by experimental data. Simulations revealed influences in both directions, stabilizing the ring-septum system as a whole. By providing a smooth circular anchoring surface for the ring, the inner septum leading edge stabilized ring organization and tension production; by mechanically regulating septum circularity and in-plane growth, ring tension stabilized septum growth and shape. Genetic or pharmacological perturbation of either subsystem destabilized this delicate balance, precipitating uncontrolled positive feedback with disastrous morphological and functional consequences. Thus, high curvature septum irregularities triggered bridging instabilities, in which contractile ring segments became unanchored. Bridging abolished the local tension-mediated septum shape regulation, exacerbating the irregularity in a mutually destabilizing runaway process. Our model explains a number of previously mysterious experimental observations, including unanchoring of ring segments observed in cells with mutations in the septum-growing {beta}-glucan synthases, and irregular septa in cells with mutations in the contractile ring myosin-II Myo2. Thus, the contractile ring and cell wall growth cellular machineries operate as a single integrated system, whose stability relies on mutual regulation by the two subsystems.