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

Jacco Van Rheenen, Xiaoyan Song, Wies Van Roosmalen, Michael Cammer, Xiaoming Chen, Vera M. Desmarais, Shu Chin Yip, Jonathan M. Backer, Robert J. Eddy, John S. Condeelis

Research output: Contribution to journalArticle

174 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)1247-1259
Number of pages13
JournalJournal of Cell Biology
Volume179
Issue number6
DOIs
StatePublished - Dec 17 2007

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Actin Depolymerizing Factors
Epidermal Growth Factor
Microfilament Proteins
Hydrolysis
Carcinoma
Actins
Phosphoinositide Phospholipase C
Chemotactic Factors
Chemotaxis
Actin Cytoskeleton
Polymerization
Cell Movement
Breast Neoplasms
Neoplasm Metastasis
Membranes

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

Cite this

EGF-induced PIP2 hydrolysis releases and activates cofilin locally in carcinoma cells. / Van Rheenen, Jacco; Song, Xiaoyan; Van Roosmalen, Wies; Cammer, Michael; Chen, Xiaoming; Desmarais, Vera M.; Yip, Shu Chin; Backer, Jonathan M.; Eddy, Robert J.; Condeelis, John S.

In: Journal of Cell Biology, Vol. 179, No. 6, 17.12.2007, p. 1247-1259.

Research output: Contribution to journalArticle

Van Rheenen, Jacco ; Song, Xiaoyan ; Van Roosmalen, Wies ; Cammer, Michael ; Chen, Xiaoming ; Desmarais, Vera M. ; Yip, Shu Chin ; Backer, Jonathan M. ; Eddy, Robert J. ; Condeelis, John S. / EGF-induced PIP2 hydrolysis releases and activates cofilin locally in carcinoma cells. In: Journal of Cell Biology. 2007 ; Vol. 179, No. 6. pp. 1247-1259.
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AU - Chen, Xiaoming

AU - Desmarais, Vera M.

AU - Yip, Shu Chin

AU - Backer, Jonathan M.

AU - Eddy, Robert J.

AU - Condeelis, John S.

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