Wnt5a signaling promotes apical and basolateral polarization of single epithelial cells

Single epithelial-derived tumor cells have been shown to induce apical and basolateral (AB) polarity by expression of polarization-related proteins. However, physiological cues and molecular mechanisms for AB polarization of single normal epithelial cells are unclear. When intestinal epithelial cell...

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Bibliographic Details
Published in:Molecular biology of the cell 2013-12, Vol.24 (23), p.3764-3774
Main Authors: Gon, Hidetoshi, Fumoto, Katsumi, Ku, Yonson, Matsumoto, Shinji, Kikuchi, Akira
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - metabolism
Animals
Cell Polarity - drug effects
Cell Shape - drug effects
Chlorocebus aethiops
Collagen - pharmacology
Dishevelled Proteins
Drug Combinations
Enterocytes - cytology
Enterocytes - drug effects
Enterocytes - ultrastructure
Epithelial Cells - cytology
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Epithelial Cells - ultrastructure
Green Fluorescent Proteins - metabolism
Guanine Nucleotide Exchange Factors - metabolism
HEK293 Cells
HeLa Cells
Humans
Laminin - pharmacology
Microvilli - drug effects
Microvilli - metabolism
Microvilli - ultrastructure
Neoplasm Proteins - metabolism
Phosphoproteins - metabolism
Protein Transport - drug effects
Proteoglycans - pharmacology
rac1 GTP-Binding Protein - metabolism
Rats
Repressor Proteins - metabolism
rho GTP-Binding Proteins - metabolism
Signal Transduction - drug effects
T-Lymphoma Invasion and Metastasis-inducing Protein 1
Vero Cells
Wnt Proteins - metabolism
Wnt-5a Protein
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Summary:Single epithelial-derived tumor cells have been shown to induce apical and basolateral (AB) polarity by expression of polarization-related proteins. However, physiological cues and molecular mechanisms for AB polarization of single normal epithelial cells are unclear. When intestinal epithelial cells 6 (IEC6 cells) were seeded on basement membrane proteins (Matrigel), single cells formed an F-actin cap on the upper cell surface, where apical markers accumulated, and a basolateral marker was localized to the rest of the cell surface region, in a Wnt5a signaling-dependent manner. However, these phenotypes were not induced by type I collagen. Rac1 activity in the noncap region was higher than that in the cap region, whereas Rho activity increased toward the cap region. Wnt5a signaling activated and inhibited Rac1 and RhoA, respectively, independently through Tiam1 and p190RhoGAP-A, which formed a tertiary complex with Dishevelled. Furthermore, Wnt5a signaling through Rac1 and RhoA was required for cystogenesis of IEC6 cells. These results suggest that Wnt5a promotes the AB polarization of IEC6 cells through regulation of Rac and Rho activities in a manner dependent on adhesion to specific extracellular matrix proteins.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.e13-07-0357