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

Autor: Eddy Pasquier, Peter W. Gunning, Christine Chaponnier, Sela T. Po'uha, Geraldine M. O'Neill, Michael S.Y. Shum, Maria Kavallaris
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Pyridines
ddc:616.07
Biochemistry
0302 clinical medicine
Wound Healing/physiology
Cell Movement
Cell polarity
Myosin
RNA
Small Interfering
Phosphorylation
Cytoskeleton
Rho-Associated Kinases/metabolism
Pyridines/pharmacology
RNA
Small Interfering/genetics
0303 health sciences
rho-Associated Kinases
Cell Polarity
Cell migration
Cell Polarity/physiology
Cofilin
Cell biology
030220 oncology & carcinogenesis
Gene Knockdown Techniques
RNA Interference
Biotechnology
Signal Transduction
Myosin Light Chains
macromolecular substances
Biology
Focal Adhesions/physiology
Models
Biological
Cell Line
Focal adhesion
03 medical and health sciences
Genetics
Humans
Molecular Biology
Protein Kinase Inhibitors
Actin
Paxillin
030304 developmental biology
Amides/pharmacology
Focal Adhesions
Wound Healing
Base Sequence
Actins/antagonists & inhibitors/genetics/metabolism
Cell Movement/physiology
Amides
Actins
Protein Kinase Inhibitors/pharmacology
Paxillin/metabolism
biology.protein
Myosin Light Chains/metabolism
Zdroj: FASEB Journal, Vol. 25, No 12 (2011) pp. 4423-33
FASEB journal : official publication of the Federation of American Societies for Experimental Biolog
ISSN: 0892-6638
Popis: 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.
Databáze: OpenAIRE
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