The Crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-β-SMAD pathway - PubMed (original) (raw)

The Crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-β-SMAD pathway

Xaralabos Varelas et al. Dev Cell. 2010.

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Abstract

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-β-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-β 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-β signaling. Accordingly, disruption of the Crumbs complex enhances TGF-β signaling and predisposes cells to TGF-β-mediated epithelial-to-mesenchymal transitions.

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Comment in

Cell signalling: Weighing up TGFβ signals.
Schuldt A. Schuldt A. Nat Rev Mol Cell Biol. 2011 Feb;12(2):76. doi: 10.1038/nrm3050. Epub 2011 Jan 12. Nat Rev Mol Cell Biol. 2011. PMID: 21224888 No abstract available.
Cell signalling: weighing up TGFβ signals.
Schuldt A. Schuldt A. Nat Rev Cancer. 2011 Feb;11(2):82. doi: 10.1038/nrc3011. Nat Rev Cancer. 2011. PMID: 21322293

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The Crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-β-SMAD pathway - PubMed (original) (raw)