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Published online
doi:10.1083/jcb.200806030
The Journal of Cell Biology, Vol. 183, No. 3, 543-554
The Rockefeller University Press, 0021-9525 $30.00
© Vicente-Manzanares et al.
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Article

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



Miguel Vicente-Manzanares1, Margaret A. Koach1, Leanna Whitmore1, Marcelo L. Lamers2, and Alan F. Horwitz1

1 Department of Cell Biology, University of Virginia, Charlottesville, VA 22908
2 Department of Cell and Developmental Biology, Biomedical Sciences Institute, University of São Paulo SP05508-000, Brazil

Correspondence to Miguel Vicente-Manzanares: mvicente{at}virginia.edu

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 filament bundles and adhesions, which locally inhibit protrusion and define the morphology of the tail. Myosin IIA forms de novo filaments 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-specific 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 isoforms during filament 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.

Abbreviations used in this paper: FRAP, fluorescence recovery after photobleaching; MEF, mouse embryonic fibroblast; MLC, myosin light chain.

© 2008 Vicente-Manzanares et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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