Latrunculin A Depolymerizes Actin Filaments by Binding Terminal Subunits and by Sequestering Actin Monomers

Abstract

Latrunculin A (LatA) is the widely used reagent to depolymerize actin filaments. Its mechanism has been thought that LatA sequesters actin monomers from polymerization. Recent observation of single actin filaments by TIRF microscopy found that the binding affinity of LatA to actin monomers depends on the nucleotide status on actin. The observation of actin filaments also showed that LatA binds to actin filaments. LatA increased the depolymerization rate at ends of filaments assembled from ATP-actin to the rates of ADP-actin, but did not change these rates of ADP- or ADP-Pi-bound actin filaments. LatA also severed actin filaments. Thermodynamic analysis proposes that LatA accelerates phosphate release only at ends of actin filaments. Rapid depolymerization, severing and sequestering monomers are mechanisms of LatA to inhibit cellular actin cytoskeleton.