MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford, OX3 9DS, UK.
Howard Hughes Medical Institute, Janelia Research Campus, 19700 Helix Drive, Ashburn, VA, 20147, USA.
Commun Biol. 2019 Mar 7;2:93. doi: 10.1038/s42003-019-0322-9. eCollection 2019.
Activation of immune cells relies on a dynamic actin cytoskeleton. Despite detailed knowledge of molecular actin assembly, the exact processes governing actin organization during activation remain elusive. Using advanced microscopy, we here show that Rat Basophilic Leukemia (RBL) cells, a model mast cell line, employ an orchestrated series of reorganization events within the cortical actin network during activation. In response to IgE antigen-stimulation of FCε receptors (FCεR) at the RBL cell surface, we observed symmetry breaking of the F-actin network and subsequent rapid disassembly of the actin cortex. This was followed by a reassembly process that may be driven by the coordinated transformation of distinct nanoscale F-actin architectures, reminiscent of self-organizing actin patterns. Actin patterns co-localized with zones of Arp2/3 nucleation, while network reassembly was accompanied by myosin-II activity. Strikingly, cortical actin disassembly coincided with zones of granule secretion, suggesting that cytoskeletal actin patterns contribute to orchestrate RBL cell activation.
免疫细胞的激活依赖于动态的肌动蛋白细胞骨架。尽管人们对分子肌动蛋白组装有详细的了解，但在激活过程中控制肌动蛋白组织的确切过程仍然难以捉摸。在这里，我们使用先进的显微镜技术显示，大鼠嗜碱性白血病（RBL）细胞，一种模型肥大细胞系，在激活过程中在皮质肌动蛋白网络内采用一系列协调的重组事件。在 RBL 细胞表面的 IgE 抗原刺激 FCε 受体（FCεR）后，我们观察到 F-肌动蛋白网络的对称性破坏以及随后肌动蛋白皮质的快速解体。随后是一个可能由不同纳米级 F-肌动蛋白结构的协调转化驱动的重新组装过程，类似于自组织的肌动蛋白模式。肌动蛋白模式与 Arp2/3 成核区共定位，而网络的重新组装伴随着肌球蛋白-II 活性。引人注目的是，皮质肌动蛋白的解体与颗粒分泌区重合，这表明细胞骨架肌动蛋白模式有助于协调 RBL 细胞的激活。
