Journal
JOURNAL OF CELL BIOLOGY
Volume 166, Issue 5, Pages 697-708Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200405156
Keywords
PLC; actin; P13 kinase; motility; chemotaxis
Categories
Funding
- NCI NIH HHS [P01 CA100324, CA100324] Funding Source: Medline
- NIGMS NIH HHS [GM38511, R01 GM038511] Funding Source: Medline
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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.
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