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Published online September 15, 2008
doi:10.1083/jcb.200712086
The Journal of Cell Biology, Vol. 182, No. 6, 1217-1230
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Hirano et al.
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Article

EPB41L5 functions to post-transcriptionally regulate cadherin and integrin during epithelial–mesenchymal transition

Mariko Hirano1,4, Shigeru Hashimoto4, Shigenobu Yonemura3, Hisataka Sabe4, and Shinichi Aizawa1,2

1 Laboratory for Vertebrate Body Plan, 2 for Animal Resources and Genetic Engineering, and 3 for Cellular Morphogenesis, Center for Developmental Biology (CDB), RIKEN Kobe, Chuo-ku, Kobe 650-0047, Japan
4 Department of Molecular Biology, Osaka Bioscience Institute, Suita-shi, Osaka 565-0874, Japan

Correspondence to Shinichi Aizawa: saizawa{at}cdb.riken.jp

EPB41L5 belongs to the band 4.1 superfamily. We investigate here the involvement of EPB41L5 in epithelial–mesenchymal transition (EMT) during mouse gastrulation. EPB41L5 expression is induced during TGFβ-stimulated EMT, whereas silencing of EPB41L5 by siRNA inhibits this transition. In EPB41L5 mutants, cell–cell adhesion is enhanced, and EMT is greatly impaired during gastrulation. Moreover, cell attachment, spreading, and mobility are greatly reduced by EPB41L5 deficiency. Gene transcription regulation during EMT occurs normally at the mRNA level; EPB41L5 siRNA does not affect either the decrease in E-cadherin or the increase in integrin expression. However, at the protein level, the decrease in E-cadherin and increase in integrin are inhibited in both EPB41L5 siRNA-treated NMuMG cells and mutant mesoderm. We find that EPB41L5 binds p120ctn through its N-terminal FERM domain, inhibiting p120ctn–E-cadherin binding. EPB41L5 overexpression causes E-cadherin relocalization into Rab5-positive vesicles in epithelial cells. At the same time, EPB41L5 binds to paxillin through its C terminus, enhancing integrin/paxillin association, thereby stimulating focal adhesion formation.

Abbreviations used in this paper: Crb, Crumbs; EMT, epithelial–mesenchymal transition; p120ctn, p120 catenin.

© 2008 Hirano et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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