Mechanically induced septin networks protect nuclear integrity.

The cytoskeleton is a key mediator of mechanical interactions in cells, but specific contributions of septins remain unclear. Septins preferentially localize with a subset of actin stress fibers positioned under the nucleus, where they are situated between the membrane and stress fibers. Removing the nucleus from the cell results in the loss of these subnuclear septin-decorated stress fibers. Surprisingly, however, their formation can be rescued using a large glass bead in place of the nucleus. Similarly, applying a compressive force to the cell via confinement, whether externally or through internally generated actomyosin forces, results in increased septin accumulation in regions where the nucleus engages the cell cortex. Finally, loss of septin filaments via knockdown of SEPT7 increases nuclear membrane rupture during confinement. Together, these data argue that septins act as a dynamic mechanosensitive protective network to buffer mechanical forces on the nucleus.