Baranov Maksim V, Revelo Natalia H, Verboogen Daniëlle R J, Ter Beest Martin, van den Bogaart Geert
a Department of Tumor Immunology , Radboud University Medical Center, Radboud Institute for Molecular Life Sciences , Nijmegen , The Netherlands.
Small GTPases. 2019 Jul;10(4):311-323. doi: 10.1080/21541248.2017.1328302. Epub 2018 Feb 9.
We recently identified a key role for SWAP70 as the tethering factor stabilizing F-actin filaments on the surface of phagosomes in human dendritic cells by interacting both with Rho-family GTPases and the lipid phosphatidylinositol (3,4)-bisphosphate. In this study, we aimed to investigate whether this role of SWAP70 was general among immune phagocytes. Our data reveal that SWAP70 is recruited to early phagosomes of macrophages and dendritic cells from both human and mouse. The putative inhibitor of SWAP70 sanguinarine blocked phagocytosis and F-actin polymerization, supporting a key role for SWAP70 in phagocytosis as demonstrated previously with knock-down. Moreover, SWAP70 was recently shown to sequester the F-actin severing protein cofilin and we investigated this relationship in phagocytosis. Our data show an increased activation of cellular cofilin upon siRNA knockdown of SWAP70. Finally, we explored whether SWAP70 would be recruited to the immune synapse between dendritic cells and T cells required for antigen presentation, as the formation of such synapses depends on F-actin. However, we observed that SWAP70 was depleted at immune synapses and specifically was recruited to phagosomes. Our data support an essential and specific role for SWAP70 in tethering and stabilizing F-actin to the phagosomal surface in a wide range of phagocytes.
我们最近发现，SWAP70作为一种拴系因子发挥关键作用，它通过与Rho家族GTP酶和脂质磷脂酰肌醇（3,4）-二磷酸相互作用，稳定人类树突状细胞吞噬体表面的F-肌动蛋白丝。在本研究中，我们旨在探究SWAP70的这一作用在免疫吞噬细胞中是否普遍存在。我们的数据显示，SWAP70被募集到人和小鼠巨噬细胞及树突状细胞的早期吞噬体上。SWAP70的假定抑制剂血根碱可阻断吞噬作用和F-肌动蛋白聚合，这支持了SWAP70在吞噬作用中起关键作用，正如之前通过敲低实验所证明的那样。此外，最近有研究表明SWAP70可隔离F-肌动蛋白切割蛋白丝切蛋白，我们在吞噬作用中研究了这种关系。我们的数据显示，在对SWAP70进行小干扰RNA敲低后，细胞内丝切蛋白的激活增加。最后，我们探讨了SWAP70是否会被募集到抗原呈递所需的树突状细胞与T细胞之间的免疫突触，因为这种突触的形成依赖于F-肌动蛋白。然而，我们观察到SWAP70在免疫突触处缺失，且特异性地被募集到吞噬体上。我们的数据支持SWAP70在多种吞噬细胞中将F-肌动蛋白拴系并稳定在吞噬体表面发挥着重要且特定的作用。
