A Temporal Model of Cofilin Regulation and the Early Peak of Actin Barbed Ends in Invasive Tumor Cells
Open accessAbstract
Cofilin is an important regulator of actin polymerization, cell migration, and chemotaxis. Recent experimental data on mammary carcinoma cells reveal that stimulation by epidermal growth factor (EGF) generates a pool of active cofilin that results in a peak of actin filament barbed ends on the timescale of 1 min. Here, we present results of a mathematical model for the dynamics of cofilin and its transition between several pools in response to EGF stimulation. We describe the interactions of phospholipase C, membrane lipids (PIP(2)), and cofilin bound to PIP(2) and to F-actin, as well as diffusible cofilin in active G-actin-monomer-bound or phosphorylated states. We consider a simplified representation in which the thin cell edge (lamellipod) and the cell interior are represented by two compartments that are linked by diffusion. We demonstrate that a high basal level of active cofilin stored by binding to PIP(2), as well as the highly enriched local milieu of F-actin at the cell edge, is essential to capture the EGF-induced barbed-end amplification observed experimentally.
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Dephosphorylated cofilin at serine-3 cleaves F-actin to generate new barbed ends and depolymerizes F-actin at its pointed end.
“Dephosphorylated cofilin at its serine-3 residue (dp-cofilin) cleaves F-actin to generate new barbed ends that are sites for actin polymerization and depolymerizes F-actin at its pointed end to reduce fiber length.”
From State-dependent diffusion of actin-depolymerizing factor/cofilin underlies the enlargement and shrinkage of dendritic spines (2016) · cites this paper as [16]
Phosphorylation of cofilin at serine-3 inhibits its actin-regulatory activities, and phosphorylated cofilin dissociates from F-actin.
“These bidirectional enzymatic activities of cofilin are inhibited by its phosphorylation at the serine-3 residue, as phosphorylated cofilin (p-cofilin) dissociates from F-actin1516.”
From State-dependent diffusion of actin-depolymerizing factor/cofilin underlies the enlargement and shrinkage of dendritic spines (2016) · cites this paper as [16]
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Noguchi, J., Hayama, T., Watanabe, S., Ucar, H., Yagishita, S., Takahashi, N., & Kasai, H. (2016) · Scientific Reports · doi:10.1038/srep32897 · Cited by 60 · see citing works
- Authors
- Tania, N., Prosk, E., Condeelis, J., & Edelstein-Keshet, L.
- Affiliations
- University of British Columbia (CA)
- Albert Einstein College of Medicine (US)
- Venue
- Biophysical Journal
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 100
- Issue
- 8
- Pages
- 1883-1892
- ISSN
- 0006-3495 (ISSN-L)
- PMC
- PMC3077689
- OpenAlex
- W2134375257
- Cited by
- 32
- References
- 0
- Citations by year
- 2025: 1 · 2024: 2 · 2021: 2 · 2020: 2 · 2018: 3 · 2017: 4 · 2016: 3 · 2015: 2 · 2014: 3 · 2013: 7 · 2012: 1
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biophysical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (R01 GM086882)
- Pacific Institute for the Mathematical Sciences
- Luonnontieteiden ja Tekniikan Tutkimuksen Toimikunta (CA150344)
- 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
- Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
- Keywords
- cofilin, epidermal growth factor, phosphatidylinositol 4,5-bisphosphate, phospholipase C, actin polymerization, lamellipod, tumor invasion, cofilin phosphorylation, mathematical model, cell migration, chemotaxis, F-actin
- MeSH terms
- Actins, Breast Neoplasms, Models, Biological, Neoplasm Invasiveness, Down-Regulation, Up-Regulation, Actin Depolymerizing Factors, Lim Kinases
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