Phospholipase C and cofilin are required for carcinoma cell directionality in response to EGF stimulation

Ghassan Mouneimne, Lilian Soon, Vera DesMarais, Mazen Sidani, Xiaoyan Song, Shu Chin Yip, Mousumi Ghosh, Robert Eddy, Jonathan M. Backer, John Condeelis

Research output: Contribution to journalArticle

196 Scopus citations

Abstract

The epidermal growth factor (EGF)-induced increase in free barbed ends, resulting in actin polymerization at the leading edge of the lamellipodium in carcinoma cells, occurs as two transients: an early one at 1 min and a late one at 3 min. Our results reveal that phospholipase (PLC) is required for triggering the early barbed end transient. Phosphoinositide-3 kinase selectively regulates the late barbed end transient. Inhibition of PLC inhibits cofilin activity in cells during the early transient, delays the initiation of protrusions, and inhibits the ability of cells to sense a gradient of EGF. Suppression of cofilin, using either small interfering RNA silencing or function-blocking antibodies, selectively inhibits the early transient. Therefore, our results demonstrate that the early PLC and cofilin-dependent barbed end transient is required for the initiation of protrusions and is involved in setting the direction of cell movement in response to EGF.

Original languageEnglish (US)
Pages (from-to)697-708
Number of pages12
JournalJournal of Cell Biology
Volume166
Issue number5
DOIs
StatePublished - Aug 30 2004

Keywords

  • Actin
  • Chemotaxis
  • Motility
  • PI3 kinase
  • PLC

ASJC Scopus subject areas

  • Cell Biology

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    Mouneimne, G., Soon, L., DesMarais, V., Sidani, M., Song, X., Yip, S. C., Ghosh, M., Eddy, R., Backer, J. M., & Condeelis, J. (2004). Phospholipase C and cofilin are required for carcinoma cell directionality in response to EGF stimulation. Journal of Cell Biology, 166(5), 697-708. https://doi.org/10.1083/jcb.200405156