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- W4319931869 abstract "In eukaryotic cells, spatiotemporal control of actin dynamics is crucial to regulate essential functions. Cellular structure, behavior and response to stimuli are directly regulated by the economy of actin monomers within different cellular networks. This is obtained by tightly regulating the rates of polymerization, depolymerization, and regeneration of actin monomers. Unfortunately, treadmilling of actin alone cannot sustain the volume of polymerization necessary to maintain cellular functions, since the rate of subunit loss becomes prohibitive to generating a constant pool of polymerizable actin monomers. Faster depolymerization can be achieved by a) manipulating the number of filament ends, and b) increasing the availability of monomers. Combination of Profilin and Cofilin leads to a synergistic rise in ATP consumption during bulk actin polymerization. This presents us with two possibilities where either the monomer becomes limiting or the nucleotide. From pyrene-actin traces we concluded that presence of Cofilin and Profilin together suppresses the initial rate of polymerization of the filament but does not change the critical concentration. To observe the effect of this cocktail on individual filaments, we reconstituted actin filaments in vitro and measured rates of filament severing and monomer dissociation. Despite no evidence of binding to filament sides, Profilin enhances Cofilin mediated filament severing in a dose dependent manner. Addition of Profilin also accelerates Cofilin mediated subunit loss from the barbed end of filaments. Using wildtype and mutant variants of Cofilin we also demonstrate that Profilin's effect on monomer dissociation in presence of Cofilin is distinct from its effect on severing by Cofilin. We present macroscopic evidence of direct interplay between Cofilin and Profilin to enhance barbed end monomer dissociation at Profilin concentrations much lower than previously reported." @default.
- W4319931869 created "2023-02-11" @default.
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- W4319931869 date "2023-02-01" @default.
- W4319931869 modified "2023-09-25" @default.
- W4319931869 title "Profilin enhances cofilin induced actin dynamics" @default.
- W4319931869 doi "https://doi.org/10.1016/j.bpj.2022.11.2214" @default.
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