Journal
JOURNAL OF CELL SCIENCE
Volume 127, Issue 13, Pages 2840-2848Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.139246
Keywords
Interferon regulatory factor 6; Migration; Keratinocytes
Categories
Funding
- National Institutes of Health [AR035313, 5T35HL007485-34]
- National Science Foundation [1120478]
- Developmental Studies Hybridoma Bank at the University of Iowa, a National Resource
- National Institutes of Health
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1120478] Funding Source: National Science Foundation
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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.
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