title: The structure of the macrophage actin skeleton.
abstract: The actin skeleton of the macrophage consists of a three-dimensional network of actin filaments and associated proteins. The organization of this multiprotein structure is regulated at several levels in cells. Receptor stimulation induces a massive actin polymerization at the cell cortex, changes in cell shape and active cellular movements. Gelsolin may have a pivotal role in restructuring the actin skeleton in response to agonist stimulation, as the activity of this potent actin-modulating protein is regulated by both Ca2+ and polyphosphoinositides. Micromolar concentrations of Ca2+ activate gelsolin to bind to the sides of actin filaments, sever, and cap the filament end. Polyphosphoinositides, in particular PIP and PIP2, release gelsolin from the filament ends. A structure-function analysis of gelsolin indicates that its N-terminal half is primarily responsible for severing actin filaments, and elucidates mechanisms by which Ca2+ and phospholipid may regulate gelsolin functions. The ultrastructure of actin filaments in the macrophage cortical cytoplasm is regulated, to a large extent, by the actin cross-linking protein, actin-binding protein (ABP) which defines filament orthogonality.
authors.affiliation: Hematology-Oncology Unit, Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: H L
authors.initials: HL
authors.lastname: Yin
authors.forename: J H
authors.initials: JH
authors.lastname: Hartwig
mesh_terms: D000199:Actins / Q000502:physiology*; D000818:Animals; D002135:Calcium-Binding Proteins / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D018260:Gelsolin; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000648:ultrastructure; D008840:Microfilament Proteins / Q000502:physiology; D008855:Microscopy, Electron, Scanning; D011817:Rabbits; D013329:Structure-Activity Relationship
chemical_list: D000199:Actins; D002135:Calcium-Binding Proteins; D018260:Gelsolin; D008840:Microfilament Proteins