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Dual function of Src in the maintenance of adherens junctions during tracheal epithelial morphogenesis
Masayo Shindo1, Housei Wada, Masako Kaido
1Riken Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku Kobe 650-0047, Japan.
Abstract:
The downregulation of E-cadherin by Src promotes epithelial to mesenchymal transition and tumorigenesis. However, a simple loss of cell adhesion is not sufficient to explain the diverse developmental roles of Src and metastatic behavior of viral Src-transformed cells. Here, we studied the functions of endogenous and activated forms of Drosophila Src in the context of tracheal epithelial development, during which extensive remodeling of adherens junctions takes place. We show that Src42A is selectively activated in the adherens junctions of epithelia undergoing morphogenesis. Src42A and Src64B are required for tracheal development and to increase the rate of adherens junction turnover. The activation of Src42A caused opposing effects: it reduced the E-cadherin protein level but stimulated transcription of the E-cadherin gene through the activation of Armadillo and TCF. This TCF-dependent pathway was essential for the maintenance of E-cadherin expression and for tissue integrity under conditions of high Src activity. Our data suggest that the two opposing outcomes of Src activation on E-cadherin facilitate the efficient exchange of adherens junctions, demonstrating the key role of Src in the maintenance of epithelial integrity.
Insights
Src kinase activity in Drosophila regulates epithelial integrity by modulating E-cadherin. This dual effect on E-cadherin levels and gene expression is crucial for cell adhesion dynamics during development.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Biology
Background:
- Src tyrosine kinase is implicated in epithelial to mesenchymal transition and tumorigenesis through E-cadherin downregulation.
- The precise roles of Src in developmental processes and cell adhesion dynamics remain incompletely understood.
Purpose of the Study:
- To investigate the function of endogenous and activated Drosophila Src in tracheal epithelial development.
- To elucidate the mechanisms by which Src influences adherens junctions and E-cadherin during morphogenesis.
Main Methods:
- Studied endogenous and activated forms of Drosophila Src (Src42A and Src64B) in tracheal epithelial development.
- Analyzed Src activation at adherens junctions during epithelial morphogenesis.
- Investigated the effects of Src activation on E-cadherin protein levels and gene transcription via Armadillo and TCF pathways.
Main Results:
- Src42A is selectively activated in adherens junctions during tracheal epithelial morphogenesis.
- Src42A and Src64B are essential for tracheal development and increase adherens junction turnover rate.
- Src42A activation paradoxically reduced E-cadherin protein but increased E-cadherin gene transcription through Armadillo/TCF, maintaining tissue integrity.
Conclusions:
- Src plays a critical role in maintaining epithelial integrity by dynamically regulating adherens junctions.
- The opposing effects of Src on E-cadherin (protein reduction and gene stimulation) facilitate efficient junctional exchange.
- Src-mediated regulation of E-cadherin is crucial for tissue development and integrity under dynamic conditions.
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