Coordinated regulation of actin filament turnover by a high-molecular-weight Srv2/CAP complex, cofilin, profilin, and Aip1.
BACKGROUND: Dynamic remodeling of the actin cytoskeleton requires rapid turnover of actin filaments, which is regulated in part by the actin filament severing/depolymerization factor cofilin/ADF. Two factors that cooperate with cofilin are Srv2/CAP and Aip1. Human CAP enhances cofilin-mediated actin turnover in vitro, but its biophysical properties have not been ... defined, and there has been no in vivo evidence reported for its role in turnover. Xenopus Aip1 forms a cofilin-dependent cap at filament barbed ends. It has been unclear how these diverse activities are coordinated in vivo. RESULTS: Purified native yeast Srv2/CAP forms a high molecular weight structure comprised solely of actin and Srv2. The complex is linked to actin filaments via the SH3 domain of Abp1. Srv2 complex catalytically accelerates cofilin-dependent actin turnover by releasing cofilin from ADP-actin monomers and enhances the ability of profilin to stimulate nucleotide exchange on ADP-actin. Yeast Aip1 forms a cofilin-dependent filament barbed end cap, disrupted by the cof1-19 mutant. Genetic analyses show that specific combinations of activities mediated by cofilin, Srv2, Aip1, and capping protein are required in vivo. CONCLUSIONS: We define two genetically and biochemically separable functions for cofilin in actin turnover. One is formation of an Aip1-cofilin cap at filament barbed ends. The other is cofilin-mediated severing/depolymerization of filaments, accelerated indirectly by Srv2 complex. We show that the Srv2 complex is a large multimeric structure and functions as an intermediate in actin monomer processing, converting cofilin bound ADP-actin monomers to profilin bound ATP-actin monomers and recycling cofilin for new rounds of filament depolymerization.
Mesh Terms:
Actin Depolymerizing Factors, Adaptor Proteins, Signal Transducing, Cell Cycle Proteins, Chromatography, Gel, Contractile Proteins, Cytoskeletal Proteins, Electrophoresis, Polyacrylamide Gel, Gene Transfer Techniques, Immunoblotting, Microfilament Proteins, Microfilaments, Microscopy, Electron, Models, Molecular, Profilins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Serine Endopeptidases, Xenopus Proteins, src Homology Domains
Actin Depolymerizing Factors, Adaptor Proteins, Signal Transducing, Cell Cycle Proteins, Chromatography, Gel, Contractile Proteins, Cytoskeletal Proteins, Electrophoresis, Polyacrylamide Gel, Gene Transfer Techniques, Immunoblotting, Microfilament Proteins, Microfilaments, Microscopy, Electron, Models, Molecular, Profilins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Serine Endopeptidases, Xenopus Proteins, src Homology Domains
Curr. Biol.
Date: Dec. 16, 2003
PubMed ID: 14680631
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