Abstract
Cytoskeletal reorganization is essential to keratinocyte function. Rac1 regulates cytoskeletal reorganization through signaling pathways such as the cofilin cascade. Cofilin severs actin filaments after activation by dephosphorylation. Rac1 was knocked out in mouse keratinocytes and it was found that actin filaments disassembled. In the epidermis of mice in which Rac1 was knocked out only in keratinocytes, cofilin phosphorylation was aberrantly elevated, corresponding to repression of the phosphatase slingshot1 (SSH1). These effects were independent of the signaling pathways for p21-activated kinase/LIM kinase (Pak/LIMK), protein kinase C, or protein kinase D or generation of reactive oxygen species. Similarly, when actin polymerization was specifically inhibited or Rac1 was knocked down, cofilin phosphorylation was enhanced and SSH1 was repressed. Repression of SSH1 partially blocked actin depolymerization induced by Rac1 depletion. Therefore, aberrant cofilin phosphorylation that induces actin polymerization might be a consequence of actin disassembly induced by the absence of Rac1.
| Original language | English |
|---|---|
| Journal | BioFactors (Oxford, England) |
| Volume | 41 |
| Issue number | 5 |
| Pages (from-to) | 352-9 |
| Number of pages | 8 |
| ISSN | 0951-6433 |
| DOIs | |
| Publication status | Published - 1 Sept 2015 |
Keywords
- Actin Depolymerizing Factors
- Actins
- Animals
- Cells, Cultured
- Keratinocytes
- Mice
- Phosphorylation
- Reactive Oxygen Species
- Signal Transduction
- rac1 GTP-Binding Protein
- Journal Article
- Research Support, Non-U.S. Gov't