en
Scientific article
Open access
English

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

Published inThe FASEB journal, vol. 25, no. 12, p. 4423-4433
Publication date2011
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/metabolism
  • Amides/pharmacology
  • Base Sequence
  • Cell Line
  • Cell Movement/physiology
  • Cell Polarity/physiology
  • Focal Adhesions/physiology
  • Gene Knockdown Techniques
  • Humans
  • Models, Biological
  • Myosin Light Chains/metabolism
  • Paxillin/metabolism
  • Phosphorylation
  • Protein Kinase Inhibitors/pharmacology
  • Pyridines/pharmacology
  • RNA Interference
  • RNA, Small Interfering/genetics
  • Signal Transduction
  • Wound Healing/physiology
  • Rho-Associated Kinases/metabolism
Citation (ISO format)
SHUM, Michael S Y et al. γ-Actin regulates cell migration and modulates the ROCK signaling pathway. In: The FASEB journal, 2011, vol. 25, n° 12, p. 4423–4433. doi: 10.1096/fj.11-185447
Main files (1)
Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal0892-6638
639views
381downloads

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