| First Author | Biggs LC | Year | 2014 |
| Journal | J Cell Sci | Volume | 127 |
| Issue | Pt 13 | Pages | 2840-8 |
| PubMed ID | 24777480 | Mgi Jnum | J:214669 |
| Mgi Id | MGI:5603678 | Doi | 10.1242/jcs.139246 |
| Citation | Biggs LC, et al. (2014) Interferon regulatory factor 6 regulates keratinocyte migration. J Cell Sci 127(Pt 13):2840-8 |
| abstractText | Interferon regulatory factor 6 (Irf6) regulates keratinocyte proliferation and differentiation. In this study, we tested the hypothesis that Irf6 regulates cellular migration and adhesion. Irf6-deficient embryos at 10.5 days post-conception failed to close their wound compared with wild-type embryos. In vitro, Irf6-deficient murine embryonic keratinocytes were delayed in closing a scratch wound. Live imaging of the scratch showed deficient directional migration and reduced speed in cells lacking Irf6. To understand the underlying molecular mechanisms, cell-cell and cell-matrix adhesions were investigated. We show that wild-type and Irf6-deficient keratinocytes adhere similarly to all matrices after 60 min. However, Irf6-deficient keratinocytes were consistently larger and more spread, a phenotype that persisted during the scratch-healing process. Interestingly, Irf6-deficient keratinocytes exhibited an increased network of stress fibers and active RhoA compared with that observed in wild-type keratinocytes. Blocking ROCK, a downstream effector of RhoA, rescued the delay in closing scratch wounds. The expression of Arhgap29, a Rho GTPase-activating protein, was reduced in Irf6-deficient keratinocytes. Taken together, these data suggest that Irf6 functions through the RhoA pathway to regulate cellular migration. |
