The mammalian Scribble polarity protein regulates epithelial cell adhesion and migration through E-cadherin.
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 betaPIX. 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.
Qin
Yi
Y
Center for Cell Signaling, Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Capaldo
Christopher
C
Gumbiner
Barry M
BM
Macara
Ian G
IG
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D002452:Cell Count; D018797:Cell Cycle Proteins / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D020868:Gene Silencing; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D010641:Phenotype; D011485:Protein Binding; D034622:RNA Interference; D064067:Rho Guanine Nucleotide Exchange Factors; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D051178:alpha Catenin / Q000378:metabolism
D015820:Cadherins; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; C480591:SCRIB protein, human; D025521:Tumor Suppressor Proteins; D051178:alpha Catenin