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γ-Actin regulates cell migration and modulates the ROCK signaling pathway

Shum, Michael S Y
Pasquier, Eddy
Po'uha, Sela T
O'Neill, Geraldine M
Gunning, Peter W
Kavallaris, Maria
Published in FASEB Journal. 2011, vol. 25, no. 12, p. 4423-33
Abstract Cell migration plays a crucial role in numerous cellular functions, and alterations in the regulation of cell migration are required for invasive transformation of a tumor cell. While the mechanistic process of actin-based migration has been well documented, little is known as to the specific function of the nonmuscle actin isoforms in mammalian cells. Here, we present a comprehensive examination of γ-actin's role in cell migration using an RNAi approach. The partial suppression of γ-actin expression in SH-EP neuroblastoma cells resulted in a significant decrease in wound healing and transwell migration. Similarly, the knockdown of γ-actin significantly reduced speed of motility and severely affected the cell's ability to explore, which was, in part, due to a loss of cell polarity. Moreover, there was a significant increase in the size and number of paxillin-containing focal adhesions, coupled with a significant decrease in phosphorylated paxillin in γ-actin-knockdown cells. In addition, there was a significant increase in the phosphorylation of cofilin and myosin regulatory light chain, suggesting an overactivated Rho-associated kinase (ROCK) signaling pathway in γ-actin-knockdown cells. The alterations in the phosphorylation of paxillin and myosin regulatory light chain were unique to γ-actin and not β-actin knockdown. Inhibition of the ROCK pathway with the inhibitor Y-27632 restored the ability of γ-actin-knockdown cells to migrate. This study demonstrates γ-actin as a potential upstream regulator of ROCK mediated cell migration.
Keywords Actins/antagonists & inhibitors/genetics/metabolismAmides/pharmacologyBase SequenceCell LineCell Movement/physiologyCell Polarity/physiologyFocal Adhesions/physiologyGene Knockdown TechniquesHumansModels, BiologicalMyosin Light Chains/metabolismPaxillin/metabolismPhosphorylationProtein Kinase Inhibitors/pharmacologyPyridines/pharmacologyRNA InterferenceRNA, Small Interfering/geneticsSignal TransductionWound Healing/physiologyRho-Associated Kinases/metabolism
PMID: 21908715
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Research group Groupe Christine Chaponnier (pathologie et immunologie) (171)
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SHUM, Michael S Y et al. γ-Actin regulates cell migration and modulates the ROCK signaling pathway. In: FASEB Journal, 2011, vol. 25, n° 12, p. 4423-33. doi: 10.1096/fj.11-185447 https://archive-ouverte.unige.ch/unige:25621

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Deposited on : 2013-01-17

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