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- Title
γ-Actin regulates cell migration and modulates the ROCK signaling pathway.
- Authors
Shum, Michael S. Y.; Pasquier, Eddy; Po'uha, Sela T.; O'Neill, Geraldine M.; Chaponnier, Christine; Gunning, Peter W.; Kavallaris, Maria
- 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 knock- down 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 codlin and myosin regulatory light chain, suggesting an overactivated Rhoassociated 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 gamma;-actin-knockdown cells to migrate. This study demonstrates gamma;-actin as a potential upstream regulator of ROCK mediated cell migration.
- Subjects
CELL migration; CYTOLOGY; CANCER cells; ACTIN; NEUROBLASTOMA; NONMUSCLE actin
- Publication
FASEB Journal, 2011, Vol 25, Issue 12, p4423
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.11-185447