A genetic dissection of Aip1p identified sites of interactions with actin and cofilin.
Michael G. Clark, Brian Haarer, David C. Amberg
Dept. of Biochem. & Mol. Bio., SUNY Upstate Medical Univ., 750 East Adams St., Syracuse, NY, 13210, USA
Regulation of the organization and function of the actin cytoskeleton requires rapid filament turnover and modulation of turnover rates by accessory factors. Biochemical analysis suggests that cofilin and Aip1p cooperate to accelerate actin dynamics. These conserved proteins co-localize in cortical actin networks from diverse organisms. Cofilin has long been known to promote depolymerization of actin filaments by accelerating pointed-end disassembly and via a weak filament-severing activity. Aip1p dramatically enhances disassembly of actin filaments in a cofilin-dependent manner by capping the barbed ends, activating severing, or a combination of both. The mechanism of actin disassembly by the Aip1p/cofilin complex is unknown, but we favor the hypothesis that it results from increased severing due to intensification of cofilin-induced distortions of the filament structure. By mutagenesis of Aip1p, we have identified active sites on Aip1p required for the actin and cofilin interactions. Biochemical and genetic analysis of these mutants will be presented. Based on these data we will propose models for the ternary complex formed by Aip1p, cofilin, and actin, and relate these models to our filament-severing hypothesis.
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