EPB41L5 functions to post-transcriptionally regulate cadherin and integrin during epithelial-mesenchymal transition.
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 TGFbeta-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.
Hirano
Mariko
M
Laboratory for Vertebrate Body Plan, Center for Developmental Biology, RIKEN Kobe, Chuo-ku, Kobe 650-0047, Japan.
Hashimoto
Shigeru
S
Yonemura
Shigenobu
S
Sabe
Hisataka
H
Aizawa
Shinichi
S
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D003598:Cytoskeletal Proteins; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D004848:Epithelium / Q000502:physiology*; D022001:Focal Adhesions / Q000378:metabolism; D054262:Gastrulation / Q000502:physiology*; D005786:Gene Expression Regulation; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000502:physiology*; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism
D015415:Biomarkers; D015820:Cadherins; D003598:Cytoskeletal Proteins; C527074:EPB41L5 protein, mouse; D016023:Integrins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; D020696:rab5 GTP-Binding Proteins
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