| First Author | Varelas X | Year | 2010 |
| Journal | Dev Cell | Volume | 19 |
| Issue | 6 | Pages | 831-44 |
| PubMed ID | 21145499 | Mgi Jnum | J:169049 |
| Mgi Id | MGI:4939579 | Doi | 10.1016/j.devcel.2010.11.012 |
| Citation | Varelas X, et al. (2010) The Crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-beta-SMAD pathway. Dev Cell 19(6):831-44 |
| abstractText | The Hippo pathway senses cell density information to control tissue growth by regulating the localization of the transcriptional regulators TAZ and YAP (TAZ/YAP). TAZ/YAP also regulate TGF-beta-SMAD signaling, but whether this role is linked to cell density sensing is unknown. Here we demonstrate that TAZ/YAP dictate the localization of active SMAD complexes in response to cell density-mediated formation of polarity complexes. In high-density cell cultures, the Hippo pathway drives cytoplasmic localization of TAZ/YAP, which sequesters SMAD complexes, thereby suppressing TGF-beta signaling. We show that during mouse embryogenesis, this is reflected by differences in TAZ/YAP localization, which define regions of active SMAD2/3 complexes. Interfering with TAZ/YAP phosphorylation drives nuclear accumulation of TAZ/YAP and SMAD2/3. Furthermore, we demonstrate that the Crumbs polarity complex interacts with TAZ/YAP, which relays cell density information by promoting TAZ/YAP phosphorylation, cytoplasmic retention, and suppressed TGF-beta signaling. Accordingly, disruption of the Crumbs complex enhances TGF-beta signaling and predisposes cells to TGF-beta-mediated epithelial-to-mesenchymal transitions. |
