Reference - Detail
|Gon H, Fumoto K, Ku Y, Matsumoto S, Kikuchi A.
|Wnt5a signaling promotes apical and basolateral polarization of single epithelial cells.
|Mol Biol Cell
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.
|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 Rats Repressor Proteins / metabolism Signal Transduction / drug effects T-Lymphoma Invasion and Metastasis-inducing Protein 1 Vero Cells Wnt Proteins / metabolism* Wnt-5a Protein rac1 GTP-Binding Protein / metabolism rho GTP-Binding Proteins / metabolism