The filamins: properties and functions

The filamins are a group of homologous proteins defined by their high native molecular weight (500,000), their amino acid compositions, their cross-reactivity to antibodies to heterologous filamins, their localization to actin networks and bundles in situ, and their ability to cross-link actin filaments in vitro into three-dimensional networks and bundles. Native filamins contain two subunits (relative mass = 250 000). Each subunit carries at least one actin-binding site and formation of bivalent dimers is therefore believed to explain filamin's ability to cross-link actin filaments. Formation of networks in vitro (corresponding to formation of macroscopic gels) has been analyzed using the theory of Flory. As predicted, a sharp transition to gel (at the critical gelation concentration of filamin) is observed when actin is mixed with increasing concentrations of filamin and the critical gelation concentration is found to vary inversely with the length of actin filaments. However, the measured values of the critical gelation concentration are all higher (2- to 14-fold) than predicted by the theory and the prediction that the critical concentration varies directly with the actin concentration was verified with only one of two techniques used. Filamin's length (160-190 nm) and flexibility (1000-fold greater than actin filaments) may make it especially well fitted to cross-link actin filaments into three-dimensional networks when present in low molar ratios (1:200 to 1:50) relative to actin. At higher molar ratios (greater than 1:20) it also cross-links actin filaments into bundles. Assuming that filamin actually helps organize supramolecular structures inside cells (not yet tested directly), then its concentration relative to actin may help determine whether networks or bundles are formed. Other factors that may influence its localization and function inside cells include competition with other actin-binding proteins (such as myosin and tropomyosin) for binding sites on actin and phosphorylation, which may alter its ability to bind to actin.