The Actin Cytoskeleton: Regulation of Actin Filament Assembly and Disassembly

Abstract

Eukaryotic cells possess three kinds of cytoskeletal elements: 5- to 9-nmdiameter actin filaments, 24-nm-diameter microtubules, and 10-nmdiameter intermediate filaments. All these polymer networks are assembled reversibly from monomers. This chapter concentrates on actin. Reorganization of the actin cytoskeleton is required for leukocytes to migrate to sites of infection, for fibroblasts and endothelial cells to migrate to areas of wound healing, and for platelets to plug leaking vessels. Actin polymerization not only drives the motility of leukocytes, fibroblasts, keratocytes, and amoebae, but also provides the propulsive force for the movement of intracellular bacteria including Listeria, Shigella, and Rickettsia as well as the poxvirus, vaccinia. The severing of actin filaments reduces the viscosity of the peripheral cytoplasm and allows the actin cytoskeleton to be rapidly remodeled. When cells are stimulated to move and change shape, the number of free barbed filament ends markedly increases. This rapid rise in the number of free barbed ends can be accomplished in two ways. First, the barbed ends of preformed actin filaments can be uncapped and second, nucleating proteins can serve as a template to initiate the elongation of new actin filaments. The precise mechanisms regulating the formation of new actin filaments in the motile cell remain to be determined. In addition, filaments can be severed by gelsolin. The combination of uncapping and severing can greatly increase the number of free barbed-filament ends available for rapid actin assembly.