Tara up-regulates E-cadherin transcription by binding to the Trio RhoGEF and inhibiting Rac signaling

Tomoki Yano , Yuji Yamazaki , Makoto Adachi , Katsuya Okawa , Philippe Fort (1) , Masami Uji , Shoichiro Tsukita (2) , Sachiko Tsukita (2)

1 CRBM - Centre de recherche en Biologie Cellulaire
2 Faculty of Medicine

The spatiotemporal regulation of E-cadherin expression is important during body plan development and carcinogenesis. We found that Tara (Trio-associated repeat on actin) is enriched in cadherin-based adherens junctions (AJs), and its knockdown in MDCK cells (Tara-KD cells) significantly decreases the expression of E-cadherin. Tara-KD activates Rac1 through the Trio RhoGEF, which binds to E-cadherin and subsequently increases the phosphorylation of p38 and Tbx3, a transcriptional E-cadherin repressor. Accordingly, the decrease in E-cadherin expression is abrogated by ITX3 and SB203580 (specific inhibitors of Trio RhoGEF and p38MAPK, respectively), and by dephosphomimetic Tbx3. Despite the decreased E-cadherin expression, the Tara-KD cells do not undergo an epithelial-mesenchymal transition and remain as an epithelial cell sheet, presumably due to the concomitant up-regulation of cadherin-6. Tara-KD reduces the actin-belt density in the circumferential ring, and the cells form flattened cysts, suggesting that Tara functions to modulate epithelial cell sheet formation and integrity by up-regulating E-cadherin transcription.

Domaines: Biologie moléculaire; Embryologie et organogenèse; Cancer; Systématique, phylogénie et taxonomie; Organisation et fonctions cellulaires [q-bio.SC]

Tomoki Yano, Yuji Yamazaki, Makoto Adachi, Katsuya Okawa, Philippe Fort, et al.. Tara up-regulates E-cadherin transcription by binding to the Trio RhoGEF and inhibiting Rac signaling. Journal of Cell Biology, 2011, 193 (2), pp.319-332. ⟨10.1083/jcb.201009100⟩. ⟨hal-02267376⟩