Filamin-A Sample Clauses

Filamin-A. The activity of the Rho GTPases is also regulated by Filamin-A (Xxxxxxx et al., 2001). Filamin-A is an actin filament binding and cross-linking protein that has been shown to influence the architecture and organisation of the actin cytoskeleton (Xxxxxxxx et al., 2001; Xxxx et al., 1975), (figure 1.5). Filamin-A first acquired its name due to the fact that it was found to localise with actin filaments (Xxxx et al., 1975). There are 3 human Filamins (Filamin-A, B and C); all of them display actin-filament cross-linking activity while maintaining the capacity of attaching binding partners to the plasma membrane (xxx xxx Xxxxx and Xxxxxxxxxx, 2001). Ultimately, through these features, filamins contribute to the complex cytoskeletal architecture adopted by migrating cells (Xxxxxxx et al., 2001). Filamins are found as homo-dimers of large peptide chains that associate with each other via their C-termini. The actin binding domain (ABD) consisting of two calponin homology domains lies at the far N-terminus of each monomer and its similar to those found in other actin binding domains such as α-actinin and calponin (xxx xxx Xxxxx and Xxxxxxxxxx, 2001). Following the ABD, each filamin monomer contains 2 rod domains made of 24 anti-parallel β-sheets. These are interrupted by two calpain sensitive hinge domains (Xxxxxxxx et al., 2007; Xxxxxxx et al., 2001). The rod domains mediate the interactions with binding partners while the hinge domains contribute to the elasticity observed in the actin networks reconstituted in vitro (Xxxxxx et al., 2006). Ultimately, dimerization results in a Y shape of the filamin dimer which enables the cross- linking activity of the protein (Xxxxxxxx et al., 2007), (figure 1.10). The association of Filamin-A with cytoskeletal dynamics already suggests that Filamin-A is important in cell migration. This is well characterised in M2 melanoma cells lacking Filamin-A expression compared to the M2 sub-line A7 that express Filamin-A. Indeed, M2 cells make unstable protrusions and blebs while displaying compromised migration. Unlike the M2 cells, Filamin-A reconstituted A7 cells displayed improved elasticity, protrusion stability and cell motility (Xxxxxxxxxx et al., 1992). Interestingly, similar levels of Arp2/3 were detected in both cell types further confirming the importance of Filamin-A in regulating cytoskeletal architecture and stability (Xxxxxxxx et al., 2001). Consistent with this, Filamin-A binds Rac1, Cdc42 and RhoA although the functiona...