TY - JOUR
T1 - A temporal model of cofilin regulation and the early peak of actin barbed ends in invasive tumor cells
AU - Tania, Nessy
AU - Prosk, Erin
AU - Condeelis, John
AU - Edelstein-Keshet, Leah
N1 - Funding Information:
This research was supported by a subcontract (to L.E.K.) from the National Institutes of Health (Grant No. R01 GM086882) to Anders Carlsson, Washington University, and by a Natural Sciences and Engineering Research Council discovery grant (to L.E.K.). J.C. is funded by National Institutes of Health grant CA150344. E.P. was supported by an International Graduate Training Center fellowship from the Pacific Institute for the Mathematical Sciences (Canada).
PY - 2011/4/20
Y1 - 2011/4/20
N2 - 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 (PIP2), and cofilin bound to PIP2 and to F-actin, as well as diffusible cofilin in active G-actinmonomer-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 PIP2, 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.
AB - 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 (PIP2), and cofilin bound to PIP2 and to F-actin, as well as diffusible cofilin in active G-actinmonomer-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 PIP2, 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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U2 - 10.1016/j.bpj.2011.02.036
DO - 10.1016/j.bpj.2011.02.036
M3 - Article
C2 - 21504724
AN - SCOPUS:79959729826
SN - 0006-3495
VL - 100
SP - 1883
EP - 1892
JO - Biophysical journal
JF - Biophysical journal
IS - 8
ER -