Kuhn Thomas B, Bamburg James R
Department of Chemistry, University of Alaska Fairbanks, Fairbanks, Alaska, USA.
Adv Exp Med Biol. 2008;644:232-49. doi: 10.1007/978-0-387-85766-4_18.
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.
肌动蛋白丝的动力学对于许多基本细胞过程至关重要，如胞质分裂、细胞运动、形态形成、囊泡和细胞器运输、基因转录以及衰老。肌动蛋白丝动力学的体内动力学与体外平衡相差甚远，这些显著差异归因于大量的调节蛋白。特别是，ADF/丝切蛋白家族的蛋白质通过切断肌动蛋白丝并增强ADP - 肌动蛋白单体从其尖端的解聚作用，极大地增加了肌动蛋白丝的动力学。丝切蛋白协同结合到F - 肌动蛋白的一种次要构象上，其中亚基沿着丝螺旋轴略有欠旋转。在丝切蛋白与肌动蛋白亚基的化学计量比很高时，丝切蛋白实际上会稳定肌动蛋白丝。许多原肌球蛋白同工型似乎与ADF/丝切蛋白家族蛋白竞争结合肌动蛋白丝。迄今为止研究的原肌球蛋白同工型更喜欢结合F - 肌动蛋白的“未扭曲”构象，并通过它们对F - 肌动蛋白的保护和稳定作用，募集肌球蛋白II并从丝切蛋白 - 肌动蛋白丝组装不同的肌动蛋白超结构。然而，一些原肌球蛋白同工型可能与ADF/丝切蛋白协同作用以增强丝动力学，这表明原肌球蛋白的不同同工型，其中许多具有发育或组织特异性表达谱，在肌动蛋白超结构的组装和周转中起主要作用。不同的肌动蛋白超结构可以在细胞内空间和时间上重叠，但可以根据它们的动力学和运动学特性彼此区分。此外，通过信号转导途径对ADF/丝切蛋白活性进行局部调节可能是改变亚细胞区域中某些原肌球蛋白同工型与F - 肌动蛋白结合动态平衡的一种机制。
