EPB41L5 functions to post-transcriptionally regulate cadherin and integrin during epithelial-mesenchymal transition.
EPB41L5 functions to post-transcriptionally regulate cadherin and integrin during epithelial-mesenchymal transition.
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DOI：
10.1083/jcb.200712086
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发表时间：
2008-09-22
期刊：
影响因子：
--
通讯作者：
Aizawa S
中科院分区：
文献类型：
--
作者：
Hirano M;Hashimoto S;Yonemura S;Sabe H;Aizawa S
EPB 41 L5属于带4.1超家族。我们在这里调查EPB 41 L5参与上皮间质转化（EMT）在小鼠原肠胚形成。EPB 41 L5的表达在TGFβ刺激的EMT过程中被诱导，而通过siRNA沉默EPB 41 L5抑制了这种转变。在EPB 41 L5突变体中，细胞-细胞粘附增强，并且在原肠胚形成期间EMT大大受损。此外，EPB 41 L5缺陷会大大降低细胞的附着、扩散和移动性。EMT过程中的基因转录调控通常发生在mRNA水平; EPB 41 L5 siRNA不影响E-cadherin的减少或整合素表达的增加。然而，在蛋白质水平上，E-cadherin的减少和整合素的增加在EPB 41 L5 siRNA处理的NMuMG细胞和突变体中胚层中均受到抑制。我们发现EPB 41 L5通过其N-末端FERM结构域结合p120 ctn，抑制p120 ctn-E-钙粘蛋白结合。EPB 41 L5过表达导致上皮细胞中E-钙粘蛋白重新定位到Rab 5阳性囊泡中。同时，EPB 41 L5通过其C末端与桩蛋白结合，增强整联蛋白/桩蛋白缔合，从而刺激粘着斑形成。
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.
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影响因子：
5.3
作者：
Palacios, F;Tushir, JS;D'Souza-Schorey, C
通讯作者：
D'Souza-Schorey, C
影响因子：
19
作者：
D'Souza-Schorey, C
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5.3
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作者：
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de Herreros, AG