Response Gene to Complement 32 Protein Promotes Macrophage Phagocytosis via Activation of Protein Kinase C Pathway
Response Gene to Complement 32 Protein Promotes Macrophage Phagocytosis via Activation of Protein Kinase C Pathway
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DOI：
10.1074/jbc.m114.566653
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发表时间：
2014-08-15
影响因子：
4.8
通讯作者：
Chen, Shi-You
中科院分区：
文献类型：
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作者：
Tang, Rui;Zhang, Gui;Chen, Shi-You
巨噬细胞吞噬在宿主防御中起着重要作用。然而，其分子机制，特别是调控吞噬作用的因素，尚不完全清楚。在本研究中，我们发现补体32应答基因（RGC-32）是一个重要的吞噬调节因子。虽然RGC-32在单核-巨噬细胞分化过程中被诱导并在巨噬细胞中大量表达，但RGC-32在这一过程中似乎并不重要，因为缺乏RGC-32的骨髓祖细胞通常可以分化为巨噬细胞。然而，缺乏RGC-32的腹腔巨噬细胞和骨髓源性巨噬细胞均表现出明显的吞噬缺陷，而过表达RGC-32的巨噬细胞则表现出增强的吞噬能力。机制上，RGC-32被招募到巨噬细胞膜，在那里它促进f -肌动蛋白的组装和吞噬杯的形成。RGC-32敲除会损害f -肌动蛋白的组装。RGC-32似乎与PKC相互作用，调节PKC诱导的f -肌动蛋白交联蛋白肉豆蔻酰基化富丙氨酸蛋白激酶C底物的磷酸化。综上所述，我们的研究结果首次证明了RGC-32是一种新的巨噬细胞吞噬膜调节剂。
Macrophage phagocytosis plays an important role in host defense. The molecular mechanism, especially factors regulating the phagocytosis, however, is not completely understood. In the present study, we found that response gene to complement 32 (RGC-32) is an important regulator of phagocytosis. Although RGC-32 is induced and abundantly expressed in macrophage during monocyte-macrophage differentiation, RGC-32 appears not to be important for this process because RGC-32-deficient bone marrow progenitor can normally differentiate to macrophage. However, both peritoneal macrophages and bone marrow-derived macrophages with RGC-32 deficiency exhibit significant defects in phagocytosis, whereas RGC-32-overexpressed macrophages show increased phagocytosis. Mechanistically, RGC-32 is recruited to macrophage membrane where it promotes F-actin assembly and the formation of phagocytic cups. RGC-32 knock-out impairs F-actin assembly. RGC-32 appears to interact with PKC to regulate PKC-induced phosphorylation of F-actin cross-linking protein myristoylated alanine-rich protein kinase C substrate. Taken together, our results demonstrate for the first time that RGC-32 is a novel membrane regulator for macrophage phagocytosis.