Abstract |
To address the functions of Rac1 in keratinocytes of the basal epidermal layer and in the outer root sheath of hair follicles, we generated transgenic mice expressing a dominant inhibitory mutant of Rac, N17Rac1, under the control of the keratin 14 promoter. These mice do not exhibit an overt skin phenotype but show protracted skin wound re-epithelialization. Investigation into the underlying mechanisms revealed that in vivo both proliferation of wound-edge keratinocytes and centripetal migration of the neo-epidermis were impaired. Similar results were obtained in mice with an epidermis-specific deletion of Rac1. Primary epidermal keratinocytes that expressed the N17Rac1 transgene were less proliferative than control cells and showed reduced ERK1/2 phosphorylation upon growth factor stimulation. Adhesion, spreading, random migration and closure of scratch wounds in vitro were significantly inhibited on collagen I and, to a lesser extent, on fibronectin. Stroboscopic analysis of cell dynamics (SACED) of N17Rac1 transgenic and control keratinocytes identified decreased lamella-protrusion persistence in connection with increased ruffle frequency as a probable mechanism for the observed impairment of keratinocyte adhesion and migration. We conclude that Rac1 is functionally required for normal epidermal wound healing and, in this context, exerts a dual function - namely the regulation of keratinocyte proliferation and migration.
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Authors | Michael Tscharntke, Ruth Pofahl, Anna Chrostek-Grashoff, Neil Smyth, Carien Niessen, Catherin Niemann, Benedikt Hartwig, Volker Herzog, Helmut W Klein, Thomas Krieg, Cord Brakebusch, Ingo Haase |
Journal | Journal of cell science
(J Cell Sci)
Vol. 120
Issue Pt 8
Pg. 1480-90
(Apr 15 2007)
ISSN: 0021-9533 [Print] England |
PMID | 17389689
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- RAC1 protein, human
- rac1 GTP-Binding Protein
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Topics |
- Animals
- Cell Adhesion
(physiology)
- Cell Movement
(physiology)
- Cell Proliferation
- Epidermis
(physiopathology)
- Keratinocytes
(cytology)
- Wound Healing
- rac1 GTP-Binding Protein
(genetics, physiology)
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