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.
Highlights
The concerted dissociation and re-establishment of cell-cell adhesion in epithelial cells is essential for morphogenesis, but studies of the cellular bases of those processes have begun only recently (Bertet et al, 2004; Ribeiro et al, 2004; Zallen and Wieschaus, 2004)
To monitor Src activity in Drosophila tissues, we used antibodies directed to the phosphotyrosine residue of Src that is essential for its activation (Y400 of Src42A, hereafter called pSrc; Fig. 1A) (Kmiecik and Shalloway, 1987; Piwnica-Worms et al, 1987). pSrc was detected preferentially in adherens junctions (AJs) of epithelial tissues (Fig. 1B-D), whereas the anti-Src42A antibody detected signals outlining many types of cells (Fig. 1D) (Takahashi et al, 2005)
Dual function Src in the turnover of AJs The turnover of cell adhesion proteins at the AJs is a key target for regulators of tissue morphogenesis
Summary
The concerted dissociation and re-establishment of cell-cell adhesion in epithelial cells is essential for morphogenesis, but studies of the cellular bases of those processes have begun only recently (Bertet et al, 2004; Ribeiro et al, 2004; Zallen and Wieschaus, 2004). The cell adhesion molecule E-cadherin is concentrated at the adherens junctions (AJs) and plays a key organizing role in epithelial morphogenesis (Takeichi, 1991) through its interaction with -catenin and ␣-catenin, which forms a dynamically regulated molecular link between cadherins and the actin cytoskeleton (Drees et al, 2005; Yamada et al, 2005). A recent study suggests that Src might act positively on cell adhesion (McLachlan et al, 2007). Src elicits effects on a number of signaling pathways and multiple mammalian SFKs have overlapping functions, making genetic analyses via gene
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
