Molecular Cell Biology Laboratory, Department of Neurology, University Hospital Regensburg, D-93053 Regensburg, Germany.
J Cell Sci. 2023 Mar 15;136(6). doi: 10.1242/jcs.260743. Epub 2023 Mar 30.
Looking back at two decades of research on SPIRE actin nucleator proteins, the first decade was clearly dominated by the discovery of SPIRE proteins as founding members of the novel WH2-domain-based actin nucleators, which initiate actin filament assembly through multiple WH2 actin-binding domains. Through complex formation with formins and class 5 myosins, SPIRE proteins coordinate actin filament assembly and myosin motor-dependent force generation. The discovery of SPIRE-regulated cytoplasmic actin filament meshworks in oocytes initiated the next phase of SPIRE research, which has found that SPIRE proteins are integrated in a diverse range of cell biological processes. In addition to regulating vesicle-based actin filament meshworks, SPIRE proteins function in the organisation of actin structures driving the inward movement of pronuclei of the mouse zygote. Localisation at cortical ring structures and the results of knockdown experiments indicate that SPIRE proteins function in the formation of meiotic cleavage sites in mammalian oocytes and the externalisation of von Willebrand factor from endothelial cells. Alternative splicing targets mammalian SPIRE1 towards mitochondria, where it has a role in fission. In this Review, we summarise the past two decades of SPIRE research by addressing the biochemical and cell biological functions of SPIRE proteins in mammalian reproduction, skin pigmentation and wound healing, as well as in mitochondrial dynamics and host-pathogen interactions.
回顾 SPIRE 肌动蛋白成核蛋白二十年的研究，第一个十年显然以发现 SPIRE 蛋白作为新型 WH2 结构域肌动蛋白成核因子的创始成员为主，这些因子通过多个 WH2 肌动蛋白结合结构域启动肌动蛋白丝组装。SPIRE 蛋白通过与formin 和 5 类肌球蛋白形成复合物，协调肌动蛋白丝组装和肌球蛋白马达依赖的力产生。在卵母细胞中发现 SPIRE 调节的细胞质肌动蛋白丝网格网络引发了 SPIRE 研究的下一个阶段，该阶段发现 SPIRE 蛋白整合在多种细胞生物学过程中。除了调节基于囊泡的肌动蛋白丝网格网络外，SPIRE 蛋白还在驱动小鼠受精卵原核内移的肌动蛋白结构组织中发挥作用。皮层环结构的定位和敲低实验的结果表明，SPIRE 蛋白在哺乳动物卵母细胞减数分裂位点的形成和血管内皮细胞 von Willebrand 因子的外化中发挥作用。哺乳动物 SPIRE1 的选择性剪接靶标朝向线粒体，在那里它在分裂中发挥作用。在这篇综述中，我们通过探讨 SPIRE 蛋白在哺乳动物生殖、皮肤色素沉着和伤口愈合以及线粒体动力学和宿主-病原体相互作用中的生化和细胞生物学功能，总结了过去二十年的 SPIRE 研究。
