How profilin/barbed-end synergy controls actin polymerization: a kinetic model of the ATP hydrolysis circuit

Cell Motility and the Cytoskeleton
P A Dufort, C J Lumsden

Abstract

The role of ATP hydrolysis in the regulation of the actin cytoskeleton continues to be a subject of controversy. Since actin polymerization can occur in the absence of ATP, the energy of hydrolysis is not needed for filament assembly. Recent work has instead suggested a regulatory role for ATP in cytoskeletal remodeling. In particular, both profilin and free filament barbed ends have been shown to play major roles in the processing of ATP by actin. We have developed a new integrated kinetic model to examine how the maintenance of the pool of unpolymerized actin and the flux of actin subunits through filaments are controlled by profilin and free filament barbed ends through their interaction with ATP. An analysis of the model's steady states predicts how two novel regulatory pathways may regulate the cytoskeleton in vivo. Coordinated changes in the availability of both profilin and free barbed ends mediate the following regulatory effects: (1) both the nucleotide composition and the absolute amount of free G-actin can be changed separately or together to substantially alter the total amount of F-actin; and (2) uncapping the barbed ends of only a modest fraction of filaments causes all filaments to begin slowly depolymerizing fro...Continue Reading

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