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Type: Journal article
Title: Regulation of focal adhesions by Flightless I involves inhibition of paxillin phosphorylation via a Rac1-dependent pathway
Author: Kopecki, Z.
O'Neill, G.
Arkell, R.
Cowin, A.
Citation: Journal of Investigative Dermatology, 2011; 131(7):1450-1459
Publisher: Blackwell Publishing Inc
Issue Date: 2011
ISSN: 0022-202X
Statement of
Zlatko Kopecki, Geraldine M. O'Neill, Ruth M. Arkell and Allison J. Cowin
Abstract: Flightless I (Flii) is an actin-remodeling protein that influences diverse processes including cell migration and gene transcription and links signal transduction with cytoskeletal regulation. Here, we show that Flii modulation of focal adhesions and filamentous actin stress fibers is Rac1-dependent. Using primary skin fibroblasts from Flii overexpressing (FliiTg/Tg), wild-type, and Flii deficient (Flii+/−) mice, we show that elevated expression of Flii increases stress fiber formation by impaired focal adhesion turnover and enhanced formation of fibrillar adhesions. Conversely, Flii knockdown increases the percentage of focal complex positive cells. We further show that a functional effect of Flii at both the cellular level and in in vivo mouse wounds is through inhibiting paxillin tyrosine phosphorylation and suppression of signaling proteins Src and p130Cas, both of which regulate adhesion signaling pathways. Flii is upregulated in response to wounding, and overexpression of Flii inhibits paxillin activity and reduces adhesion signaling by modulating the activity of the Rho family GTPases. Overexpression of constitutively active Rac1 GTPase restores the spreading ability of FliiTg/Tg fibroblasts and may explain the reduced adhesion, migration, and proliferation observed in FliiTg/Tg mice and their impaired wound healing, a process dependent on effective cellular motility and adhesion.
Keywords: F-actin, filamentous actin
Flii, Flightless I
WT, wild type
Rights: © 2011 The Society for Investigative Dermatology
DOI: 10.1038/jid.2011.69
Appears in Collections:Aurora harvest
Paediatrics publications

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