Flightless I Regulates Hemidesmosome Formation and Integrin-Mediated Cellular Adhesion and Migration during Wound Repair

Date

2009

Authors

Kopecki, Zlatko
Arkell, Ruth
Powell, Barry C
Cowin, Allison

Journal Title

Journal ISSN

Volume Title

Publisher

Nature Publishing Group

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 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.

Description

Keywords

Keywords: alpha3 integrin; alpha6 integrin; beta1 integrin; beta4 integrin; collagen type 1; laminin; laminin binding protein; tetraspanin; transcription factor Fli 1; actin filament; animal cell; animal experiment; animal model; animal tissue; article; cell adhesi

Citation

Source

The Journal of Investigative Dermatology

Type

Journal article

Book Title

Entity type

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License Rights

DOI

10.1038/jid.2008.461

Restricted until

2037-12-31