Membrane-tethered syntaxin-4 locally abrogates E-cadherin function and activates Smad signals, contributing to asymmetric mammary epithelial morphogenesis
| Autor: | Kota Shirai, Yohei Hirai, Yuina Hirose |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition Organogenesis Cell Morphogenesis SMAD Smad2 Protein Biochemistry 03 medical and health sciences Mice Downregulation and upregulation Extracellular medicine Animals Epithelial–mesenchymal transition Breast Smad3 Protein Molecular Biology Cadherin Chemistry Qa-SNARE Proteins Epithelial Cells Cell Biology Cadherins Cell biology 030104 developmental biology medicine.anatomical_structure Intracellular Signal Transduction |
| Zdroj: | Journal of cellular biochemistry. 119(9) |
| ISSN: | 1097-4644 |
| Popis: | Spatial and temporal epithelial-mesenchymal transition (EMT) is a critical event for the generation of asymmetric epithelial architectures. We found that only restricted cell populations in the morphogenic mammary epithelia extrude syntaxin-4, a plasmalemmal t-SNARE protein, and that epithelial cell clusters with artificial heterogenic presentation of extracellular syntaxin-4 undergo asymmetric morphogenesis. A previous study revealed that inducible expression of cell surface syntaxin-4 causes EMT-like cell behaviors in the clonal mammary epithelial cells, where laminin-mediated signals were abolished so that cells readily succumb to initiate EMT. The present study added new mechanistic insight into syntaxin-4-driven EMT-like cell behaviors. Extracellular syntaxin-4 directly perturbs E-cadherin-mediated epithelial cell-cell adhesion and activates Smad signals. We found that the epithelial cells activated Smad2/3 upon induction of expression of extracellular syntaxin-4, leading to the upregulation of certain transcriptional targets of these TGF-β signaling mediators. Intriguingly, however, mRNA expression of canonical EMT initiators, such as Snail and Slug, was unchanged. In addition, E-cadherin protein was steeply decreased, yet its transcriptional expression remained constant for a couple of days. We found that extracellular syntaxin-4 directly bound to E-cadherin and sequestered β-catenin from cell-cell contact sites, perturbing intercellular adhesive property. The functional ablation of E-cadherin by syntaxin-4 was further validated by L cells with stably expressing E-cadherin, in which cells shows intercellular adhesive property solely by E-cadherin. These results underline the role of local exportation of syntaxin-4 for onset of complex epithelial morphogenesis. |
| Databáze: | OpenAIRE |
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