Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/57089
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Type: Journal article
Title: Flightless I Regulates Hemidesmosome Formation and Integrin-Mediated Cellular Adhesion and Migration during Wound Repair
Author: Kopecki, Z.
Arkell, R.
Powell, B.
Cowin, A.
Citation: Journal of Investigative Dermatology, 2009; 129(8):2031-2045
Publisher: Blackwell Publishing Inc
Issue Date: 2009
ISSN: 0022-202X
1523-1747
Statement of
Responsibility: 
Zlatko Kopecki, Ruth Arkell, Barry C. Powell and Allison J. Cowin
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 Flii(Tg/+) and Flii(Tg/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 Flii(Tg/Tg) primary keratinocytes. Decreased expression of CD151 and laminin-binding integrins alpha3, beta1, alpha6 and beta4 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.
Keywords: Flii, Flightless; PBS, phosphate-buffered saline
RMID: 0020091272
DOI: 10.1038/jid.2008.461
Appears in Collections:Surgery publications

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