title: Actin-interacting Protein 1 Promotes Disassembly of Actin-depolymerizing Factor/Cofilin-bound Actin Filaments in a pH-dependent Manner.
abstract: Actin-interacting protein 1 (AIP1) is a conserved WD repeat protein that promotes disassembly of actin filaments when actin-depolymerizing factor (ADF)/cofilin is present. Although AIP1 is known to be essential for a number of cellular events involving dynamic rearrangement of the actin cytoskeleton, the regulatory mechanism of the function of AIP1 is unknown. In this study, we report that two AIP1 isoforms from the nematode Caenorhabditis elegans, known as UNC-78 and AIPL-1, are pH-sensitive in enhancement of actin filament disassembly. Both AIP1 isoforms only weakly enhance disassembly of ADF/cofilin-bound actin filaments at an acidic pH but show stronger disassembly activity at neutral and basic pH values. However, a severing-defective mutant of UNC-78 shows pH-insensitive binding to ADF/cofilin-decorated actin filaments, suggesting that the process of filament severing or disassembly, but not filament binding, is pH-dependent. His-60 of AIP1 is located near the predicted binding surface for the ADF/cofilin-actin complex, and an H60K mutation of AIP1 partially impairs its pH sensitivity, suggesting that His-60 is involved in the pH sensor for AIP1. These biochemical results suggest that pH-dependent changes in AIP1 activity might be a novel regulatory mechanism of actin filament dynamics.
authors.affiliation: From the Departments of Pathology and Cell Biology, Emory University, Atlanta, Georgia 30322.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Nomura
authors.affiliation: the Mechanobiology Laboratory and.
authors.forename: Kimihide
authors.initials: K
authors.lastname: Hayakawa
authors.affiliation: Department of Physiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan, and the Department of Applied Biosciences, Kanazawa Institute of Technology, Kanazawa 924-0838, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tatsumi
authors.affiliation: From the Departments of Pathology and Cell Biology, Emory University, Atlanta, Georgia 30322, sono@emory.edu.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Ono
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D011817:Rabbits
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D029742:Caenorhabditis elegans Proteins; D008840:Microfilament Proteins; D020033:Protein Isoforms; C115237:actin interacting protein 1; C423987:unc-78 protein, C elegans
keywords: AIP1; actin; actin dynamics; actin turnover; cofilin; cytoskeleton; depolymerization; pH regulation; severing