title: A temporal model of cofilin regulation and the early peak of actin barbed ends in invasive tumor cells.
abstract: 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.
authors.affiliation: Department of Mathematics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Nessy
authors.initials: N
authors.lastname: Tania
authors.forename: Erin
authors.initials: E
authors.lastname: Prosk
authors.forename: John
authors.initials: J
authors.lastname: Condeelis
authors.forename: Leah
authors.initials: L
authors.lastname: Edelstein-Keshet
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D001943:Breast Neoplasms / Q000473:pathology*; D015536:Down-Regulation; D054461:Lim Kinases / Q000378:metabolism; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D015854:Up-Regulation
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D054461:Lim Kinases