Tropomyosin and ADF/cofilin as collaborators and competitors

Abstract

Dynamics of actin filaments is pivotal to many fundamental cellular processes such as Dcytokinesis, motility, morphology, vesicle and organelle transport, gene transcription and senescence. In vivo kinetics of actin filament dynamics is far from the equilibrium in vitro and these profound differences are attributed to large number of regulatory proteins. In particular, proteins of the ADF/cofilin family greatly increase actin filament dynamics by severing filaments and enhancing depolymerization of ADP-actin monomers from their pointed ends. Cofilin binds cooperatively to a minor conformer of F-actin in which the subunits are slightly under rotated along the filament helical axis. At high stoichiometry of cofilin to actin subunits, cofilin actually stabilizes actin filaments. Many isoforms oftropomyosin appear to compete with ADF/cofilin proteins for binding to actin filaments. Tropomyosin isoforms studied to date prefer binding to the "untwisted" conformer of F-actin and through their protection and stabilization of F-actin, recruit myosin II and assemble different actin superstructures from the cofilin-actin filaments. However, some tropomyosin isoforms may synergize with ADF/cofilin to enhance filament dynamics, suggesting that the different isoforms of tropomyosins, many of which show developmental or tissue specific expression profiles, play major roles in the assembly and turnover of actin superstructures. Different actin superstructures can overlap both spatially and temporally within a cell, but can be differentiated from each other based upon their kinetic and kinematic properties. Furthermore, local regulation of ADF/cofilin activity through signal transduction pathways could be one mechanism to alter the dynamic balance in F-actin-binding of certain tropomyosin isoforms in subcellular domains.