Mechanosensing Directs Mitotic Signaling Proteins to Sites of High Mechanical Stress to Regulate Cytokinesis Through a Feedback Control System

Abstract

Cytokinesis is the process by which a cell divides into two daughter cells and must be well regulated to prevent aneuploidy. The mitotic spindle is commonly viewed to initiate cleavage furrow formation through spindle signaling to the polar and furrow cortices. However, a number of studies have shown that the furrow can form independently of the mitotic spindle. Using Dictyostelium discoideum, our lab found that cellular mechanosensing is important for cell shape control during cytokinesis. Using micropipette aspiration (MPA) to apply mechanical stress to the cell cortex, we discovered that mechanical stress stimulates accumulation of myosin-II (a force-generating protein) and cortexillin-I (an actin-bundling protein) to the deformation site to correct cell shape. Both myosin-II and cortexillin-I localize to the cleavage furrow and are essential for mechanosensing. Here, we investigated how the spindle signals and mechanosensing work together to control cytokinesis. We found that the kinesin-6-family protein Kif12 can be recruited to mechanically stressed regions in a manner that is dependent on myosin-II and IQGAP2, a signaling effector of cortexillin-I. However, Kif12 is not required for myosin-II mechanosensing. Using agar overlay, we applied a uniform mechanical stress on the cortex. Previous studies showed that dividing cells under this condition have an enhancement of myosin-II localization at the cleavage furrow. In our study, we found that this enhancement is lost in kif12 nulls. We propose that spindle signaling proteins, such as Kif12, can be recruited to mechanically stressed region through the mechanosensing system. Upon recruitment to the stressed furrow cortex, spindle signals then may augment the localization of myosin-II to the cleavage furrow. Therefore, the spindle signals and mechanosensing work synergistically as a feedback control system that regulates cytokinesis.