Department of Pathology, Tennis Court Road University of Cambridge, Cambridge CB2 1QP, UK.
Int J Mol Sci. 2020 Apr 2;21(7):2457. doi: 10.3390/ijms21072457.
The small GTPase ADP-ribosylation factor 6 (Arf6) anchors at the plasma membrane to orchestrate key functions, such as membrane trafficking and regulating cortical actin cytoskeleton rearrangement. A number of studies have identified key players that interact with Arf6 to regulate actin dynamics in diverse cell processes, yet it is still unknown whether Arf6 can directly signal to the wave regulatory complex to mediate actin assembly. By reconstituting actin dynamics on supported lipid bilayers, we found that Arf6 in co-ordination with Rac1(Ras-related C3 botulinum toxin substrate 1) can directly trigger actin polymerization by recruiting wave regulatory complex components. Interestingly, we demonstrated that Arf6 triggers actin assembly at the membrane directly without recruiting the Arf guanine nucleotide exchange factor (GEF) ARNO (ARF nucleotide-binding site opener), which is able to activate Arf1 to enable WRC-dependent actin assembly. Furthermore, using labelled , we demonstrated that actin assembly by Arf6 also contributes towards efficient phagocytosis in THP-1 macrophages. Taken together, this study reveals a mechanism for Arf6-driven actin polymerization.
小分子 GTPase 二磷酸鸟苷酰化酶激活蛋白 6（Arf6）锚定于质膜，以协调关键功能，如膜运输和调节皮质肌动蛋白细胞骨架重排。许多研究已经确定了与 Arf6 相互作用的关键因子，以调节各种细胞过程中的肌动蛋白动力学，但仍不清楚 Arf6 是否可以直接向波调节复合物发出信号，以介导肌动蛋白组装。通过在支撑脂质双层上重新组装肌动蛋白动力学，我们发现 Arf6 与 Rac1（Ras 相关 C3 肉毒杆菌毒素底物 1）协调，可以通过招募波调节复合物成分直接触发肌动蛋白聚合。有趣的是，我们证明 Arf6 可以直接在膜上触发肌动蛋白组装，而无需招募能够激活 Arf1 以允许 WRC 依赖的肌动蛋白组装的 Arf 鸟嘌呤核苷酸交换因子（GEF）ARNO（ARF 核苷酸结合位点开放器）。此外，使用标记物，我们证明 Arf6 诱导的肌动蛋白组装也有助于 THP-1 巨噬细胞中的有效吞噬作用。总之，这项研究揭示了 Arf6 驱动的肌动蛋白聚合的机制。
