Mammalian SEPT2 is required for scaffolding nonmuscle myosin II and its kinases

Mammalian septin SEPT2 belongs to a conserved family of filamentous GTPases that are associated with actin stress fibers in interphase cells and the contractile ring in dividing cells. Although SEPT2 is essential for cytokinesis, its role in this process remains undefined. Here, we report that SEPT2 directly binds nonmuscle myosin ll (myosin ll), and this association is important for fully activating myosin ll in interphase and dividing cells. Inhibition of the SEPT2-myosin ll interaction in interphase cells results in loss of stress fibers, while in dividing cells this causes instability of the ingressed cleavage furrow and dissociation of the myosin ll from the Rho-activated myosin kinases ROCK and citron kinase. We propose that SEPT2-containing filaments provide a molecular platform for myosin ll and its kinases to ensure the full activation of myosin ll that is necessary for the final stages of cytokinesis.