Abstract
The adherens junction protein p120-catenin is implicated in the regulation of cadherin stability, cell migration and inflammatory responses in mammalian epithelial tissues. How these events are coordinated to promote wound repair is not understood. We show that p120 catenin regulates the intrinsic migratory properties of primary mouse keratinocytes, but also influences the migratory behavior of neighboring cells by secreted signals. These events are rooted in the ability of p120-catenin to regulate RhoA GTPase activity, which leads to a two-tiered control of cell migration. One restrains cell motility via an increase in actin stress fibers, reduction in integrin turnover and an increase in the robustness of focal adhesions. The other is coupled to the secretion of inflammatory cytokines including interleukin-24, which causally enhances randomized cell movements. Taken together, our results indicate that p120-RhoA-GTPase-mediated signaling can differentially regulate the migratory behavior of epidermal cells, which has potential implications for chronic wound responses and cancer. Synopsis The adherens junction protein p120-catenin differentially regulates the migratory behavior of primary epidermal cells via RhoA-GTPase-mediated signaling. Loss of p120-catenin restricts single cell migration intrinsically and at the same time increases the migratory behavior of neighboring cells during wound repair. Loss of p120-catenin decreases cell migration in single primary epidermal cells as a consequence of increased actin stress fibers, focal adhesion robustness and reduced integrin turnover. The restrain in cell motility is counteracted by the secretion of inflammatory factors to the environment, including IL-24, which enhances the migration of neighboring epidermal cells. The adherens junction protein p120-catenin differentially regulates the migratory behavior of primary epidermal cells via RhoA-GTPase-mediated signaling. Loss of p120-catenin restricts single cell migration intrinsically and at the same time increases the migratory behavior of neighboring cells during wound repair.
| Original language | English |
|---|---|
| Journal | E M B O Reports |
| Volume | 15 |
| Issue number | 5 |
| Pages (from-to) | 592-600 |
| Number of pages | 9 |
| ISSN | 1469-221X |
| DOIs | |
| Publication status | Published - May 2014 |
| Externally published | Yes |
Keywords
- Actin Cytoskeleton
- Animals
- Catenins
- Cell Adhesion
- Cell Movement
- Cells, Cultured
- Focal Adhesions
- Integrins
- Interleukins
- Keratinocytes
- Mice
- Signal Transduction
- Wound Healing
- rho GTP-Binding Proteins
- Journal Article
- Research Support, Non-U.S. Gov't
