The structure of the macrophage actin skeleton

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.