Phospholipase C and cofilin are required for carcinoma cell directionality in response to EGF stimulation.
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.
Mouneimne
Ghassan
G
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA. gmouneim@aecom.yu.edu
Soon
Lilian
L
DesMarais
Vera
V
Sidani
Mazen
M
Song
Xiaoyan
X
Yip
Shu-Chin
SC
Ghosh
Mousumi
M
Eddy
Robert
R
Backer
Jonathan M
JM
Condeelis
John
J
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D051339:Actin Depolymerizing Factors; D000199:Actins / Q000096:biosynthesis / Q000187:drug effects; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D008840:Microfilament Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D034622:RNA Interference; D051381:Rats; D010738:Type C Phospholipases / Q000187:drug effects / Q000378:metabolism*
D051339:Actin Depolymerizing Factors; D000199:Actins; D000906:Antibodies; D004791:Enzyme Inhibitors; D008840:Microfilament Proteins; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D010738:Type C Phospholipases