title: ADF/cofilin use an intrinsic mode of F-actin instability to disrupt actin filaments.
abstract: Proteins in the ADF/cofilin (AC) family are essential for rapid rearrangements of cellular actin structures. They have been shown to be active in both the severing and depolymerization of actin filaments in vitro, but the detailed mechanism of action is not known. Under in vitro conditions, subunits in the actin filament can treadmill; with the hydrolysis of ATP driving the addition of subunits at one end of the filament and loss of subunits from the opposite end. We have used electron microscopy and image analysis to show that AC molecules effectively disrupt one of the longitudinal contacts between protomers within one helical strand of F-actin. We show that in the absence of any AC proteins, this same longitudinal contact between actin protomers is disrupted at the depolymerizing (pointed) end of actin filaments but is prominent at the polymerizing (barbed) end. We suggest that AC proteins use an intrinsic mechanism of F-actin's internal instability to depolymerize/sever actin filaments in the cell.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia Health Sciences Center, Jordan Hall, Charlottesville, VA 22908-0733, USA.
authors.forename: Vitold E
authors.initials: VE
authors.lastname: Galkin
authors.forename: Albina
authors.initials: A
authors.lastname: Orlova
authors.forename: Margaret S
authors.initials: MS
authors.lastname: VanLoock
authors.forename: Alexander
authors.initials: A
authors.lastname: Shvetsov
authors.forename: Emil
authors.initials: E
authors.lastname: Reisler
authors.forename: Edward H
authors.initials: EH
authors.lastname: Egelman
mesh_terms: D051339:Actin Depolymerizing Factors; D000199:Actins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D051345:Destrin; D004220:Disulfides / Q000378:metabolism; D005656:Fungal Proteins; D046911:Macromolecular Substances; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism; D020836:Protein Structure, Quaternary; D011817:Rabbits
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D051345:Destrin; D004220:Disulfides; D005656:Fungal Proteins; D046911:Macromolecular Substances; D008840:Microfilament Proteins