Mechanisms of Cytokinetic Ring Constriction in Fission Yeast

Abstract

Cytokinesis, the physical process of cell division, is accomplished by constriction of an actomyosin ring in eukaryotic cells. Here we combined mathematical modeling and experiment to study ring constriction in fission yeast, a model organism as many ring components have been identified and their concentrations measured. The ring model implemented random actomyosin organization, consistent with experiment, and actin turnover mediated by formin and cofilin severing proteins with parameters determined by experimental measurements of turnover rates. An obstacle to quantitative modeling is that ring constriction is tightly coupled to the poorly understood process of septation, the deposition of new cell wall in the wake of the constricting ring. Thus we studied yeast protoplasts whose cell walls have been enzymatically digested. We found that protoplasts contain ring precursor nodes similar to normal cells and assemble functional contractile rings that constrict without septation by sliding along the plasma membrane. Thus we could directly compare model predicted ring constriction profiles to experiment. Using this approach we found constriction is driven by tensions ∼14-25 pN, far less than those measured in animal cells, and the strength of ring-membrane anchoring during constriction is ∼9 times the value of all the precursor nodes combined. The model showed ring tension requires actin anchoring and is maximized when the barbed ends are anchored. The tension magnitude is determined by a measurable statistical characteristic of the actomyosin spatial organization which quantifies actin-myosin correlations and describes the degree to which the organization possesses the optimal tension-generating sarcomeric architecture of muscle. Consistent with experiment, suppression of the actin polymerization rate increased the ring constriction time because actin filaments are shorter and hence actin-myosin coupling and tension are diminished. Thus, the model articulates a mechanistic relationship between organization, turnover kinetics and tension.