Cortical Contraction Waves at Cytokinesis of Large Cells

Abstract

Regulated changes in cortical contractility drive cytokinesis in all animal cells. In small somatic cells this regulation is dominated by microtubules: the spindle midzone positions the cytokinetic ring, while astral microtubules induce polar relaxation. However, in specialized cell types, such as oocytes, the microtubule spindle is very small relative to the cell volume and astral microtubules are very short, if present at all. Therefore, the cytokinetic signal must be transmitted to large parts of the cortex by an alternative mechanism.In these oocytes cortical contraction waves present a specialized form of cytokinetic cortical response. As expected due to the extreme difference in cell size and spindle size, our experiments show that these contraction waves are independent of microtubules. Therefore, we asked how cytokinetic signals are transduced, independent of microtubules, to the cortex.By quantifying surface curvature changes combined with imaging of fluorescent markers and inhibitor treatments, we find that the contraction wave is a band of flattening that moves across the cell driven by non-muscle myosin II (NMY2). We further find that the underlying localisation of NMY2 to the cortex is controlled by the conserved signalling module RhoA-RhoK-NMY2, which also controls contraction in the cytokinetic ring. Importantly, we find that the key cell cycle kinase, cdk1/cyclinB forms a spatial gradient across the oocyte, the low point of which sets the starting point of the contraction wave. Combining our quantitative observations with a mathematical model, we show that the spatial cdk1/cyclinB gradient combined with feedback mechanisms inherent in the RhoA-NMY2 signalling network is sufficient to explain the surface contractions. Taken together, we present a molecular-level model for surface contraction waves that identifies a conserved signalling module capable of transducing spatially and temporally organized cytokinetic signals to the cortex.