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

doi:10.1083/jcb.200405156

Published 30 August 2004. doi:10.1083/jcb.200405156
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 166, Number 5, 697-708

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

Ghassan Mouneimne¹, Lilian Soon¹, Vera DesMarais¹, Mazen Sidani¹, Xiaoyan Song¹, Shu-Chin Yip¹^,2, Mousumi Ghosh¹, Robert Eddy¹, Jonathan M. Backer², and John Condeelis¹

¹ Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461
² Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461

Address correspondence to Ghassan Mouneimne, Dept. of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Tel: (718) 430-4113. Fax: (718) 430-8996. email: gmouneim{at}aecom.yu.edu

The epidermal growth factor (EGF)–induced increase infree barbed ends, resulting in actin polymerization at the leadingedge of the lamellipodium in carcinoma cells, occurs as twotransients: an early one at 1 min and a late one at 3 min. Ourresults reveal that phospholipase (PLC) is required for triggeringthe early barbed end transient. Phosphoinositide-3 kinase selectivelyregulates the late barbed end transient. Inhibition of PLC inhibitscofilin activity in cells during the early transient, delaysthe initiation of protrusions, and inhibits the ability of cellsto sense a gradient of EGF. Suppression of cofilin, using eithersmall interfering RNA silencing or function-blocking antibodies,selectively inhibits the early transient. Therefore, our resultsdemonstrate that the early PLC and cofilin-dependent barbedend transient is required for the initiation of protrusionsand is involved in setting the direction of cell movement inresponse to EGF.

Key Words: PLC; actin; PI3 kinase; motility; chemotaxis

Abbreviations used in this paper: PI3K, phosphoinositide-3 kinase;PIP2, phosphatidyl 4,5-biphosphate; siRNA, small interferingRNA.

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