Segregation and activation of myosin IIB creates a rear in migrating cells

Abstract

We have found that MLC-dependent activation of myosin IIB in migrating cells is required to form an extended rear, which coincides with increased directional migration. Activated myosin IIB localizes prominently at the cell rear and produces large, stable actin fi lament bundles and adhesions, which locally inhibit protrusion and defi ne the morphology of the tail. Myosin IIA forms de novo fi laments away from the myosin IIB - enriched center and back to form regions that support protrusion. The positioning and dynamics of myosin IIA and IIB depend on the self-assembly regions in their coiled-coil C terminus. COS7 and B16 melanoma cells lack myosin IIA and IIB, respectively; and show isoform-specifi c front-back polarity in migrating cells. These studies demonstrate the role of MLC activation and myosin isoforms in creating a cell rear, the segregation of iso-forms during fi lament assembly and their differential effects on adhesion and protrusion, and a key role for the noncontractile region of the isoforms in determining their localization and function. © 2008 Vicente-Manzanares et al.