Graduate School of Frontier Biosciences, Osaka University

Japanese

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

Journal J Cell Biol 193, 319-32 (2011)
Authors Yano T (1), Yamazaki Y (1), Adachi M (2), Okawa K (3), Fort P (4), Uji M (1), Tsukita S (1, 2), Tsukita S (1)
  1. Laboratory of Biological Science, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan
  2. Department of Cell Biology, Faculty of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501, Japan
  3. Drug Discovery Research Laboratories, Kyowa Hakko Kirin Co., Ltd., Nagaizumi-machi, Shizuoka, 411-8731, Japan
  4. CRBM, UMSF, Université Montpellier 2 and 1, CNRS UMR 5237, Montpellier 34293, France
Title Tara up-regulates E-cadherin transcription by binding to the Trio RhoGEF and inhibiting Rac-signaling
PubMed 21482718
Laboratory Biological Science Group 〈Prof. Tsukita〉
Abstract 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.