Biol Chem. 2013 Dec;394(12):1649-60. doi: 10.1515/hsz-2013-0176.
The diversity of cellular actin functions is attained by the activation of actin nucleator complexes, which initiate the polymerization of actin monomers into a helical double-stranded filament at defined subcellular compartments. Next to actin functions at the cell membrane, including different forms of membrane protrusions and invaginations, actin dynamics at intracellular membranes has recently become a research focus. Experiments addressing the vesicle-associated Spir WH2 domain containing actin nucleators have provided novel mechanistic insights into the function of actin dynamics at intracellular membranes. Spir proteins are targeted by a modified FYVE zinc finger motif toward endosomal and vesicle membranes, where they interact and cooperate with the distinct nucleators of the FMN subfamily of formins in the nucleation of actin filaments. The function of the Spir/formin actin nucleator complex is closely related to the Rab11 small G protein, which is a key regulator of recycling and exocytic transport processes. Together with the actin motor protein and Rab11 effector myosin Vb, Spir/formin nucleated actin filaments mediate actin-dependent vesicle transport processes. Drosophila and mouse genetic studies as well as cell biology experiments point toward an important role of the Spir/formin complex in oocyte maturation and in the structure and signaling of the nervous system.
细胞肌动蛋白功能的多样性是通过肌动蛋白成核复合物的激活来实现的，这些复合物在特定的亚细胞隔室中启动肌动蛋白单体聚合形成螺旋双链丝状肌动蛋白。除了细胞膜上的肌动蛋白功能，包括不同形式的膜突起和内陷，细胞内膜上的肌动蛋白动力学最近成为研究的重点。针对与螺旋 WH2 结构域相关的囊泡相关肌动蛋白成核因子的实验，为细胞内膜上肌动蛋白动力学的功能提供了新的机制见解。Spir 蛋白被修饰的 FYVE 锌指结构域靶向内体和囊泡膜，在那里它们与 FMN 家族formin 的不同成核因子相互作用并合作，在肌动蛋白丝的成核中发挥作用。Spir/formin 肌动蛋白成核复合物的功能与 Rab11 小 G 蛋白密切相关，后者是回收和胞吐运输过程的关键调节剂。Spir/formin 成核的肌动蛋白丝与肌动蛋白马达蛋白和 Rab11 效应因子肌球蛋白 Vb 一起，介导肌动蛋白依赖性囊泡运输过程。果蝇和小鼠的遗传研究以及细胞生物学实验表明，Spir/formin 复合物在卵母细胞成熟以及神经系统的结构和信号转导中起着重要作用。
