Rotty Jeremy D, Brighton Hailey E, Craig Stephanie L, Asokan Sreeja B, Cheng Ning, Ting Jenny P, Bear James E
UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Oral Biology Curriculum, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Dev Cell. 2017 Sep 11;42(5):498-513.e6. doi: 10.1016/j.devcel.2017.08.003. Epub 2017 Aug 31.
The Arp2/3 complex nucleates branched actin, forming networks involved in lamellipodial protrusion, phagocytosis, and cell adhesion. We derived primary bone marrow macrophages lacking Arp2/3 complex (Arpc2) and directly tested its role in macrophage functions. Despite protrusion and actin assembly defects, Arpc2 macrophages competently phagocytose via FcR and chemotax toward CSF and CX3CL1. However, CR3 phagocytosis and fibronectin haptotaxis, both integrin-dependent processes, are disrupted. Integrin-responsive actin assembly and αM/β2 integrin localization are compromised in Arpc2 cells. Using an in vivo system to observe endogenous monocytes migrating toward full-thickness ear wounds we found that Arpc2 monocytes maintain cell speeds and directionality similar to control. Our work reveals that the Arp2/3 complex is not a general requirement for phagocytosis or chemotaxis but is a critical driver of integrin-dependent processes. We demonstrate further that cells lacking Arp2/3 complex function in vivo remain capable of executing important physiological responses that require rapid directional motility.
Arp2/3复合物可促使肌动蛋白形成分支，构建参与片状伪足突出、吞噬作用及细胞黏附的网络。我们培育出缺乏Arp2/3复合物（Arpc2）的原代骨髓巨噬细胞，并直接测试其在巨噬细胞功能中的作用。尽管存在突出和肌动蛋白组装缺陷，但Arpc2巨噬细胞仍能通过FcR进行有效吞噬，并向CSF和CX3CL1进行趋化运动。然而，CR3吞噬作用和纤连蛋白趋触性（二者均为整合素依赖性过程）受到破坏。在Arpc2细胞中，整合素响应性肌动蛋白组装及αM/β2整合素定位均受损。利用体内系统观察内源性单核细胞向全层耳部伤口迁移的情况，我们发现Arpc2单核细胞保持与对照相似的细胞速度和方向性。我们的研究表明，Arp2/3复合物并非吞噬作用或趋化运动的普遍必需条件，而是整合素依赖性过程的关键驱动因素。我们进一步证明，体内缺乏Arp2/3复合物功能的细胞仍能够执行需要快速定向运动的重要生理反应。
