p120-Catenin is essential for N-cadherin-mediated formation of proper junctional structure, thereby establishing cell polarity in epithelial cells.
The role of p120-catenin in the function of classical cadherins is still enigmatic despite various studies. To elucidate its role, we examined the effect of p120-catenin on the N-cadherin-mediated localization of junctional proteins in epithelial cells in this study. Cadherin-deficient MIA PaCa-2 epithelial cells did not show linear localization of tight junction proteins ZO-1 and occludin. When N-cadherin was expressed in these cells, however, the resultant transfectant cells revealed strong cell adhesion activity and linear localization of ZO-1, occludin, and N-cadherin in the lateral membrane. When the p120-catenin-binding site of N-cadherin was disrupted, the linear localization of ZO-1 and occludin disappeared, and the mutant N-cadherin became localized more diffusely in the transfectant, although the cell adhesion activity did not change much. Knockdown of p120-catenin also resulted in the very weak localization of ZO-1 and occludin. A similar effect of p120-catenin on the localization of junctional proteins was obtained under more dynamic conditions in a wound healing assay. Moreover, p120-catenin was essential for the regulation of centrosome orientation in this healing assay. Taken together, the present data indicate that p120-catenin is essential for N-cadherin-mediated formation of proper junctional structures and thereby the establishment of the cell polarity. Similar results were obtained when E-cadherin mutants comparable to those of N-cadherin were used, suggesting that p120-catenin plays the same role in the function of other classical cadherins.
Ozaki
Chisa
C
Department of Bioscience, School of Science and Technology, Kwansei Gakuin University, Sanda-shi, Hyogo-ken, Japan.
Yoshioka
Masato
M
Tominaga
Sachiko
S
Osaka
Yoshinori
Y
Obata
Shuichi
S
Suzuki
Shintaro T
ST
D001665:Binding Sites; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D051177:Catenins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D016764:Cell Polarity; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D007365:Intercellular Junctions / Q000648:ultrastructure*; D008565:Membrane Proteins / Q000032:analysis; D062793:Occludin; D010750:Phosphoproteins / Q000032:analysis; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D062826:Zonula Occludens-1 Protein; D000095002:Delta Catenin
D015820:Cadherins; D051177:Catenins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D000095002:Delta Catenin; C000722347:CTNND1 protein, human