Abstract
Adherens junctions (AJs) and tight junctions (TJs) comprise a junctional complex which plays key roles not only in cell adhesion and polarization but also in regulation of cell movement and proliferation in epithelial cells. E-Cadherin and nectin are major cell–cell adhesion molecules (CAMs) at AJs, whereas claudin is a major CAM at TJs. We have shown that the cadherin-based cell–cell adhesion is not formed in MDCK cells in which annexin II, a Ca2+- and phospholipid-binding protein, is knocked down. Here, we found that TJs and the nectin-based cell–cell adhesions were formed in annexin II-knockdown cells. The formation of TJs in annexin II-knockdown MDCK cells required the nectin-based cell–cell adhesion and afadin, a nectin- and actin-filament-binding protein. In addition, it required the activation of Cdc42 and Rac small G proteins and subsequent reorganization of the IQGAP1-dependent actin cytoskeleton which were induced by the nectin-based cell–cell adhesion. These results indicate that the nectin-based cell–cell adhesion and afadin, but not the cadherin-based cell–cell adhesion, are necessary for the formation of TJs and that the signaling by nectin and the subsequent reorganization of the actin cytoskeleton are also necessary for the formation of TJs under certain conditions.
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Acknowledgements
We are grateful to Dr M Takeichi (Center for Developmental Biology, RIKEN, Kobe, Japan) for the anti-E-cadherin mAb, Dr W Birchmeier (Max-Delbruck-Center for Molecular Medicine, Berlin, Germany) for MDCK cells, and Dr H Shibuya (Tokyo Medical and Dental University, Tokyo, Japan) for pBS-H1. The work at the Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine was supported by grants-in-aid for Scientific Research and for Cancer Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (2004, 2005).
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Yamada, A., Fujita, N., Sato, T. et al. Requirement of nectin, but not cadherin, for formation of claudin-based tight junctions in annexin II-knockdown MDCK cells. Oncogene 25, 5085–5102 (2006). https://doi.org/10.1038/sj.onc.1209525
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DOI: https://doi.org/10.1038/sj.onc.1209525
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