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PMID: 16344308 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

The Journal of cell biology ·Vol. 171 ·No. 6 ·2005-12-19 ·Pages 1061-71

Qin Y, Capaldo C, Gumbiner BM, Macara IG

Abstract

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.

MeSH Terms
Animals Cadherins/metabolism Cell Adhesion Cell Count Cell Cycle Proteins/metabolism Cell Movement Cells, Cultured Dogs Epithelial Cells/metabolism Fluorescent Antibody Technique Gene Silencing Guanine Nucleotide Exchange Factors/metabolism Humans Membrane Proteins/metabolism Microscopy, Confocal Phenotype Protein Binding RNA Interference Rho Guanine Nucleotide Exchange Factors Transfection Tumor Suppressor Proteins/metabolism alpha Catenin/metabolism
Chemicals
Cadherins Cell Cycle Proteins Guanine Nucleotide Exchange Factors Membrane Proteins Rho Guanine Nucleotide Exchange Factors SCRIB protein, human Tumor Suppressor Proteins alpha Catenin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Qin Yi
Center for Cell Signaling, Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Capaldo Christopher
Gumbiner Barry M
Macara Ian G
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200506094
Published
2005-12-19
Epub
2005-00-12
Pages
1061-71
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2171311
Subset
IM
Grants
NCI NIH HHS · P01 CA040042 · United States
NIGMS NIH HHS · R01 GM070902 · United States
NCI NIH HHS · CA040042 · United States
NIGMS NIH HHS · GM070902 · United States
External Links
PubMed source DOI: 10.1083/jcb.200506094 PMC Full Text View journal details
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