Contractile Ring Constriction And Cell Wall Growth Are Regulated By Mechanical Feedback And Destabilized By Mutations In Fission Yeast

The actomyosin contractile ring constricts and divides cells during cytokinesis, but is far from isolated. Constriction is tightly coupled to membrane addition, cortical and cytoplasmic flow and, in organisms with cell walls such as fission yeast, septation, the growth of new cell wall. These processes are highly interdependent, but the mechanisms are poorly understood. In fission yeast, this interdependence is well documented. Mutations of myosin-II in the ring produce irregular septa and inhomogeneous distributions of beta glucan synthases (Bgs) that grow cell wall, while Bgs mutations generate misshapen septa and ring-septum separation (Munoz, 2013). These findings are unexplained. Here we developed molecularly explicit simulations that fully integrate fission yeast contractile ring dynamics and cell wall growth kinetics for the first time. We find the observed irregularities originate in mechanical feedback, destabilized by mutations. In wild-type cells, mechanical communication between ring and septum growth systems regulates constriction-septation, but mutations generate positive mechanical feedback, destabilizing both interdependent systems. 3D simulations revealed a symbiotic ring-septation relationship. Ring organization depended on septum shape because ring tension pulled components to the septum tip, while irregular septum edges drastically impaired ring organization by snapping away straight bridges. Septum growth depended on ring tension, setting the ring's location and septum growth rates. In wild type simulations, the interdependence produced well-organized rings and circular septa. Ring tension suppressed septum roughness due to growth rate mechanosensitivity, while circular septa mechanically regulated ring organization. With mutated components, simulations produced defective organization matching experiment. Simulations with mutant myo2-E1 reproduced observed straight bridges, non-uniform myosin-II distribution, misshapen septa and irregular septum growth rates (Zhou et al., 2015). With mutated Bgs, rings detached into bridges and septa were misshapen (Munoz, 2013).