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Cited by 244Cellular Mechanics and InteractionsProtein Kinase Regulation and GTPase SignalingCellular transport and secretion

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

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van Rheenen, Jacco, Song, Xiaoyan, van Roosmalen, Wies, Cammer, Michael, Chen, Xiaoming, DesMarais, Vera, Yip, Shu-Chin, Backer, Jonathan M. +2 more·2007·The Journal of Cell Biology
DOI 10.1083/jcb.200706206PMC PMC2140025
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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.

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  • EGF induces rapid loss of PI(4,5)P2 through PLC activity, releasing and activating a membrane-bound pool of cofilin; cofilin severs F-actin, coincident with actin polymerisation and lamellipodium formation.

    “EGF induces a rapid loss of PI(4,5)P2 through PLC activity, resulting in release and activation of a membrane-bound pool of cofilin. Upon release, cofilin binds to and severs F-actin, which is coincident with actin polymerisation and lamellipodium formation [93].”

    From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [93]

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Authors
van Rheenen, J., Song, X., van Roosmalen, W., Cammer, M., Chen, X., DesMarais, V., Yip, S.-C., Backer, J. M., Eddy, R. J., & Condeelis, J. S.
Affiliations
  • 1Department of Anatomy and Structural Biology
  • 3Analytical Imaging Facility,
  • 2Department of Molecular Pharmacology
  • Albert Einstein College of Medicine (US)
ORCID
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2007-12-17
Volume
179
Issue
6
Pages
1247-1259
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.200706206
PMC
PMC2140025
OpenAlex
W2123836140
Cited by
244
References
0
Citations by year
2026: 2 · 2025: 6 · 2024: 4 · 2023: 4 · 2022: 9 · 2021: 4 · 2020: 8 · 2019: 9 · 2018: 5 · 2017: 11 · 2016: 16 · 2015: 20 · 2014: 11 · 2013: 24 · 2012: 19
FWCI
9.93
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5u54gm064346-10)
  • National Cancer Institute (P01CA100324, CA 100324)
  • National Institute of General Medical Sciences (U54-GM064346, GM-38511, R01GM038511)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
epidermal growth factor, phosphatidylinositol 4,5-bisphosphate, cofilin, phospholipase C, actin cytoskeleton, actin polymerization, cell chemotaxis, breast cancer cells, metastasis, actin-binding proteins
MeSH terms
Actins, Animals, Breast Neoplasms, Carcinoma, Cell Line, Cell Membrane, Epidermal Growth Factor, Female, Hydrolysis, Phosphatidylinositol 4,5-Diphosphate, Protein Transport, Actin Depolymerizing Factors, Rats

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