title: EGF-induced PIP2 hydrolysis releases and activates cofilin locally in carcinoma cells.
abstract: Lamellipodial protrusion and directional migration of carcinoma cells towards chemoattractants, such as epidermal growth factor (EGF), depend upon the spatial and temporal regulation of actin cytoskeleton by actin-binding proteins (ABPs). It is generally hypothesized that the activity of many ABPs are temporally and spatially regulated by PIP(2); however, this is mainly based on in vitro-binding and structural studies, and generally in vivo evidence is lacking. Here, we provide the first in vivo data that directly visualize the spatial and temporal regulation of cofilin by PIP(2) in living cells. We show that EGF induces a rapid loss of PIP(2) through PLC activity, resulting in a release and activation of a membrane-bound pool of cofilin. Upon release, we find that cofilin binds to and severs F-actin, which is coincident with actin polymerization and lamellipod formation. Moreover, our data provide evidence for how PLC is involved in the formation of protrusions in breast carcinoma cells during chemotaxis and metastasis towards EGF.
authors: Department of Anatomy and Structural Biology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461, USA. jvanrhee@aecom.yu.edu
authors: Jacco
authors: J
authors: van Rheenen
authors: Xiaoyan
authors: X
authors: Song
authors: Wies
authors: W
authors: van Roosmalen
authors: Michael
authors: M
authors: Cammer
authors: Xiaoming
authors: X
authors: Chen
authors: Vera
authors: V
authors: Desmarais
authors: Shu-Chin
authors: SC
authors: Yip
authors: Jonathan M
authors: JM
authors: Backer
authors: Robert J
authors: RJ
authors: Eddy
authors: John S
authors: JS
authors: Condeelis
mesh_terms: D051339:Actin Depolymerizing Factors / Q000032:analysis / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005260:Female; D006868:Hydrolysis; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000032:analysis / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D019269:Phosphatidylinositol 4,5-Diphosphate; D004815:Epidermal Growth Factor