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Published online 12 December 2005. doi:10.1083/jcb.200506094
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 171, Number 6, 1061-1071
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Article

The mammalian Scribble polarity protein regulates epithelial cell adhesion and migration through E-cadherin

Yi Qin1,2, Christopher Capaldo1,2, Barry M. Gumbiner3, and Ian G. Macara1,2

1 Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, VA 22908
2 Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908
3 Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA 22908

Correspondence to Ian G. Macara: igm9c{at}virginia.edu

Scribble (Scrib) is a conserved polarity protein required in Drosophila melanogaster for synaptic function, neuroblast differentiation, and epithelial polarization. It is also a tumor suppressor. In rodents, Scrib has been implicated in receptor recycling and planar polarity but not in apical/basal polarity. We now show that knockdown of Scrib disrupts adhesion between Madin–Darby canine kidney epithelial cells. As a consequence, the cells acquire a mesenchymal appearance, migrate more rapidly, and lose directionality. Although tight junction assembly is delayed, confluent monolayers remain polarized. These effects are independent of Rac activation or Scrib binding to ßPIX. Rather, Scrib depletion disrupts E-cadherin–mediated cell–cell adhesion. The changes in morphology and migration are phenocopied by E-cadherin knockdown. Adhesion is partially rescued by expression of an E-cadherin–{alpha}-catenin fusion protein but not by E-cadherin–green fluorescent protein. These results suggest that Scrib stabilizes the coupling between E-cadherin and the catenins and are consistent with the idea that mammalian Scrib could behave as a tumor suppressor by regulating epithelial cell adhesion and migration.

Abbreviations used in this paper: EMT, epithelial–mesenchymal transition; ERK, extracellular signal–regulated kinase; HGF, hepatocyte growth factor; KD, knockdown; PDZ, PSD-95, ZO-1, and Discs-large; RNAi, RNA interference; shRNA, small hairpin RNA.


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