EGF-induced PIP₂ hydrolysis releases and activates cofilin locally in carcinoma cells

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 a...

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Bibliographic Details
Published in:The Journal of cell biology 2007-12, Vol.179 (6), p.1247-1259
Main Authors: van Rheenen, Jacco, Song, Xiaoyan, van Roosmalen, Wies, Cammer, Michael, Chen, Xiaoming, DesMarais, Vera, Yip, Shu-Chin, Backer, Jonathan M, Eddy, Robert J, Condeelis, John S
Format: Article
Language:English
Subjects:
Actin depolymerizing factors
Actin Depolymerizing Factors - analysis
Actin Depolymerizing Factors - metabolism
Actins
Actins - metabolism
Animals
Breast Neoplasms - metabolism
Carcinoma
Carcinoma - metabolism
Cell Line
Cell lines
Cell Membrane - metabolism
Cell motility
Epidermal Growth Factor - metabolism
Female
Fluorescence
Hydrolysis
Image filters
Microfilaments
Phosphatidylinositol 4,5-Diphosphate - analysis
Phosphatidylinositol 4,5-Diphosphate - metabolism
Pixels
Protein Transport
Rats
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Summary: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 PIP₂; 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 PIP₂ in living cells. We show that EGF induces a rapid loss of PIP₂ 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.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200706206