Flightless I Regulates Hemidesmosome Formation and Integrin-Mediated Cellular Adhesion and Migration during Wound Repair
Date
2009
Authors
Kopecki, Z.
Arkell, R.
Powell, B.
Cowin, A.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Journal of Investigative Dermatology, 2009; 129(8):2031-2045
Statement of Responsibility
Zlatko Kopecki, Ruth Arkell, Barry C. Powell and Allison J. Cowin
Conference Name
Abstract
Flightless I (Flii), a highly conserved member of the gelsolin family of actin-remodelling proteins associates with actin structures and is involved in cellular motility and adhesion. Our previous studies have shown that Flii is an important negative regulator of wound repair. Here, we show that Flii affects hemidesmosome formation and integrin-mediated keratinocyte adhesion and migration. Impaired hemidesmosome formation and sparse arrangements of keratin cytoskeleton tonofilaments and actin cytoskeleton anchoring fibrils were observed in FliiTg/+ and FliiTg/Tg mice with their skin being significantly more fragile than Flii+/− and WT mice. Flii+/− primary keratinocytes showed increased adhesion on laminin and collagen I than WT and FliiTg/Tg primary keratinocytes. Decreased expression of CD151 and laminin-binding integrins α3, β1, α6 and β4 were observed in Flii overexpressing wounds, which could contribute to the impaired wound re-epithelialization observed in these mice. Flii interacts with proteins directly linked to the cytoplasmic domain of integrin receptors suggesting that it may be a mechanical link between ligand-bound integrin receptors and the actin cytoskeleton driving adhesion-signaling pathways. Therefore Flii may regulate wound repair through its effect on hemidesmosome formation and integrin-mediated cellular adhesion and migration.