Ca2+ and Calmodulin Regulate the Binding of Filamin A to Actin Filaments

Amino- and carboxyl-terminal domains of Filamin-A interact with CRMP1 to mediate Sema3A signalling

“…40). Interestingly, these residues are overlapped with the Calmodulin-Ca binding residues, Thr50-Arg96, in ABD 24 . Thus, as the Calmodulin-Ca complex binding to ABD reduces the interaction of Filamin-A and F-actin, CRMP1 binding to ABD may also inhibit the interaction.…”

“…Filamin-A interacts with numerous intracellular signalling proteins 23 . The binding of Calmodulin-Ca complex to ABD inhibits the interaction of ABD and F-actin 24 . Rho family GTPases and their regulators, such as Trio and FilGAP, bind to .…”

The filamins

“…However, Flna-null mice do exhibit a thinning of the cerebral cortex that may indicate a migration defect. 94,95 The blebbing mode is also regulated by the RhoA-ROCK pathway that induces myosin contraction and antagonizes the Rac1-WAVE pathway, which induces actin polymerization-dependent protrusions (mesenchymal migration mode). Suppression of Rac1 activity is catalyzed by ARHGAP22 whose activity is regulated by actinomyosin contractility through an unknown mechanism, rather than by direct phosphorylation by ROCK.…”

Filamin structure, function and mechanics: are altered filamin-mediated force responses associated with human disease?

“…Factin polymerisation is a local phenomenon in cells prevalent at the cell membrane and around extracellular matrix contact focal adhesion sites (Pollard and Cooper 2009) where FLN is also localised (Langanger et al 1984;Nikki et al 2002). FLN binds F-actin with moderate affinity K d 0.13-3.2 μM (Nomura et al 1987;Ohta and Hartwig 1995), an interaction that can be regulated by inositol phospholipids (Furuhashi et al 1992), Ca 2+ -calmodulin (Nakamura et al 2005) and phosphorylation (Ohta and Hartwig 1995). Most actin binding proteins have affinities for F-actin in the μM range suggesting that having many interaction partners with moderate binding affinity conveys a high degree of dynamic elasticity upon the Factin cytoskeleton (Goldmann et al 1997).…”