An end in sight: tropomodulin

TIN filaments are required for cell locomotion and numerous intracellular activities in nonmuscle cells, and are a major component of the contractile apparatus in muscle cells. An understanding of the dynamics involved in the assembly and disassembly of actin filaments is fundamental to understanding many cellular functions. In this issue of The Journal of Cell Biology, Weber et al. (1994b) provide important new insights as to how actin assembly and disassembly is regulated in the cell with their demonstration of tropomodulin as a capping protein specific for the kinetically less active end of an actin filament. Filament formation is a dynamic and polarized process (for review see Pollard and Cooper, 1986). In the absence of other proteins, actin monomers self-assemble in vitro into filaments reaching many microns in length. Assembly begins with the formation of nuclei containing three or four actin monomers. Elongation of the nuclei proceeds with the addition of monomers, but net growth at each end is not to the same extent. Monomers add to the kinetically more active ("barbed" or "preferred") end 10 times as quickly as to the less active ("pointed" or "nonpreferred") end. At equilibrium, the filaments are not static and monomers are both adding and dissociating from both ends of the filaments, albeit at different rates. In vivo a number of actin accessory proteins exists which regulate filament assembly, for example, by associating with monomers thereby sequestering them from participating in assembly, or by capping the ends of actin filaments thereby preventing monomer exchange at that end (for a review on actin-binding proteins, see Hartwig and Kwiatkowski, 1991). Capping results in regulation of filament length and stabilization against disassembly. Proteins such as gelsolin (Yin and Stossel, 1979; Wang and Bryan, 1981) and villin (Bretscher and Weber, 1980; Glenney et al., 1981) are calcium-sensitive actin-binding proteins which both sever actin filaments and cap the barbed ends of actin filaments thereby preventing monomer exchange. Other capping proteins such as macrophage-capping protein (Southwick and DiNubile, 1986) or gcap39 (Yu et al., 1990) also cap the barbed ends of actin filaments in a calcium-sensitive manner, but do not sever actin filaments. Capping protein from Acanthamoeba (Isenberg et al., 1980) and capZ from muscle (Caldwell et al., 1989) bind to the barbed ends of actin ilia-