Myosin II is an Active Stress Sensor at the Core of a Cell Division Control System

Abstract

Mechanosensing is important in many cellular processes such as cell motility and cell division. Cells experience mechanical stress from the surrounding environment and also its internal cytoskeleton structure. Previous studies from our lab showed that cellular mechanosensing is crucial for regulating cytokinesis shape change. Using micropipette aspiration (MPA) to generate stress on the cell cortex, we discovered that mechanical stress stimulates the accumulation of myosin-II (a contractile force generating protein) and cortexillin-I (an actin bundling protein) at the deformation site. These proteins then contract the cortex, correcting the shape of the cell. Both myosin-II and cortexillin-I are required for this mechanosensory system during cytokinesis. Recently, we demonstrated that this mechanosensory response is tunable by varying the lever arm length of myosin-II heavy chain, showing that myosin-II is an active force sensor in this mechanosensory system. We now focus on how mechanical inputs mediated through myosin-II lead to changes in biochemical signaling pathways, specifically the cortexillin-I regulatory and spindle signaling pathways. Rac1A (a small GTPase), IQGAP1, and IQGAPA (GTPase effectors) can form complexes with cortexillin-I. In the absence of both IQGAP1 and IQGAPA, cortexillin-I does not localize normally to the cleavage furrow during cell division. However, IQGAPA, but not IQGAP1, is required for myosin-II mechanosensing. Kif12, a mitotic-kinesin-like protein in Dictyostelium cells, is part of the chromosomal passenger complex, including INCENP and Aurora kinase. Kif12 is also recruited to the cell cortex inside the micropipette in a myosin-II-dependent and/or IQGAPA-dependent manner during cell division. Thus, mitotic spindle signaling proteins are responsive to mechanical stress sensed by myosin-II. Overall, myosin-II is a key mechanical stress sensor and these mechanical inputs are fed back to the mitotic spindle signaling system.