Coordination of Fc receptor signaling regulates cellular commitment to phagocytosis
Coordination of Fc receptor signaling regulates cellular commitment to phagocytosis
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DOI：
10.1073/pnas.1008248107
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发表时间：
2010-11-09
影响因子：
11.1
通讯作者：
Swanson, Joel A.
中科院分区：
文献类型：
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作者：
Zhang, Youxin;Hoppe, Adam D.;Swanson, Joel A.
在巨噬细胞通过Fcγ受体（FcR）介导的吞噬作用过程中，细胞质通过质膜上FcR的顺序连接在IgG包被的颗粒上推进。如果FcR信号传导是完全自主的，那么吞噬过程中产生的信号应该与连接的受体数量成正比。通过测量对不同密度IgG包被的珠子的FcR依赖性反应，本研究发现了在颗粒摄取过程中组织全或无反应的非线性信号传导。低密度IgG包被珠子的吞噬作用要么在形成小的、富含肌动蛋白的杯状结构后停滞，要么以与高密度IgG珠子吞噬相同的速率完成。通过量化黄色荧光蛋白（YFP）标记的探针向吞噬杯膜的募集来测量信号。尽管早期信号的强度与IgG密度相关，但后期信号显示出全或无反应，这是由吞噬杯膜中3'磷酸肌醇的浓度调节的。因此，先前已表明是吞噬作用所必需的3'磷酸肌醇，在一种影响晚期而非早期信号的反馈调节机制中起作用。这表明了一种由受体信号传导引发的细胞运动协调机制。
During Fc gamma receptor (FcR)-mediated phagocytosis by macrophages, cytoplasm advances over IgG-coated particles by the sequential ligation of FcR in plasma membranes. If FcR signaling was strictly autonomous, then the signals generated during phagocytosis should be proportional to the number of ligated receptors. By measuring FcR-dependent responses to beads coated with various densities of IgG, this study identified nonlinear signaling that organizes an all or none response during particle ingestion. Phagocytosis of beads with IgG at low density either stalled after making small, actin-rich cups or proceeded to completion at the same rate as phagocytosis of high-density IgG beads. Signals were measured by quantifying the recruitment of YFP-labeled probes to phagocytic cup membranes. Although the magnitude of early signals correlated with IgG density, later signals showed an all or none response, which was regulated by the concentrations of 3' phosphoinositides in phagocytic cup membranes. Thus, 3' phosphoinositides, shown previously to be required for phagocytosis, function in a feedback regulatory mechanism affecting late but not early signals. This indicates a mechanism for the coordination of cell movements initiated by receptor signaling.