title: Aip1 promotes actin filament severing by cofilin and regulates constriction of the cytokinetic contractile ring.
abstract: Aip1 (actin interacting protein 1) is ubiquitous in eukaryotic organisms, where it cooperates with cofilin to disassemble actin filaments, but neither its mechanism of action nor its biological functions have been clear. We purified both fission yeast and human Aip1 and investigated their biochemical activities with or without cofilin. Both types of Aip1 bind actin filaments with micromolar affinities and weakly nucleate actin polymerization. Aip1 increases up to 12-fold the rate that high concentrations of yeast or human cofilin sever actin filaments, most likely by competing with cofilin for binding to the side of actin filaments, reducing the occupancy of the filaments by cofilin to a range favorable for severing. Aip1 does not cap the barbed ends of filaments severed by cofilin. Fission yeast lacking Aip1 are viable and assemble cytokinetic contractile rings normally, but rings in these Δaip1 cells accumulate 30% less myosin II. Further, these mutant cells initiate the ingression of cleavage furrows earlier than normal, shortening the stage of cytokinetic ring maturation by 50%. The Δaip1 mutation has negative genetic interactions with deletion mutations of both capping protein subunits and cofilin mutations with severing defects, but no genetic interaction with deletion of coronin.
authors.affiliation: From the Departments of Molecular Cellular and Developmental Biology.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: From the Departments of Molecular Cellular and Developmental Biology.
authors.forename: Naomi
authors.initials: N
authors.lastname: Courtemanche
authors.affiliation: From the Departments of Molecular Cellular and Developmental Biology, Molecular Biophysics and Biochemistry, and Cell Biology Yale University, New Haven, Connecticut 06520-8103 thomas.pollard@yale.edu.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Pollard
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry; D048749:Cytokinesis; D017353:Gene Deletion; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009154:Mutation; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D012568:Schizosaccharomyces / Q000378:metabolism*; D013696:Temperature; D020798:Two-Hybrid System Techniques
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D008840:Microfilament Proteins; D011994:Recombinant Proteins; C115237:actin interacting protein 1; D000255:Adenosine Triphosphate
keywords: Actin; Aip1; Cofilin; Cytokinesis; Myosin; Severing; Yeast