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Science 320 (5874): 365-369

Copyright © 2008 by the American Association for the Advancement of Science

Wnt5a Control of Cell Polarity and Directional Movement by Polarized Redistribution of Adhesion Receptors

Eric S. Witze,1 Elizabeth S. Litman,1,2 Gretchen M. Argast,1 Randall T. Moon,3,2 Natalie G. Ahn1,2*

Abstract: Mechanisms by which Wnt pathways integrate the organization of receptors, organelles, and cytoskeletal proteins to confer cell polarity and directional cell movement are incompletely understood. We show that acute responses to Wnt5a involve recruitment of actin, myosin IIB, Frizzled 3, and melanoma cell adhesion molecule into an intracellular structure in a melanoma cell line. In the presence of a chemokine gradient, this Wnt-mediated receptor–actin–myosin polarity (W-RAMP) structure accumulates asymmetrically at the cell periphery, where it triggers membrane contractility and nuclear movement in the direction of membrane retraction. The process requires endosome trafficking, is associated with multivesicular bodies, and is regulated by Wnt5a through the small guanosine triphosphatases Rab4 and RhoB. Thus, cell-autonomous mechanisms allow Wnt5a to control cell orientation, polarity, and directional movement in response to positional cues from chemokine gradients.

1 Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO80309, USA.
2 Howard Hughes Medical Institute, University of Colorado, Boulder, CO 80309, USA.
3 Department of Pharmacology and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.

* To whom correspondence should be addressed. E-mail: natalie.ahn{at}colorado.edu


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